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Yang L, Mo W, Xin L, Zhang M, Chen K, Guo X, Zhang J, Yu B. Rescuing fertility: Itaconic acid prevents ovarian damage through NRF2-mediated pyroptosis pathways in diminished ovarian reserve models. Cell Signal 2025; 131:111766. [PMID: 40147551 DOI: 10.1016/j.cellsig.2025.111766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 03/06/2025] [Accepted: 03/24/2025] [Indexed: 03/29/2025]
Abstract
BACKGROUND Diminished ovarian reserve (DOR) is a major cause of infertility, often triggered by inflammation and oxidative stress. Pyroptosis, a form of programmed cell death, has been implicated in DOR pathogenesis. Itaconic acid (IA), an endogenous metabolite, is known for its anti-inflammatory and antioxidant properties. This study aimed to explore whether IA could alleviate lipopolysaccharide (LPS)-induced DOR in mice by inhibiting pyroptosis through the NRF2 pathway. METHODS A DOR mouse model was established by administering LPS for 5 consecutive days, followed by IA treatment. Ovarian function was assessed by follicle count and hormone levels. Inflammatory markers, oxidative stress, and pyroptosis-related proteins were evaluated in both in vivo and in vitro models. The molecular mechanism was further investigated using inhibitors and molecular docking studies. RESULTS IA significantly improved ovarian function in LPS-induced DOR mice by increasing the number of follicles and normalizing hormone levels. IA also reduced inflammation, oxidative stress, and pyroptosis, as evidenced by lower expression of NLRP3, cleaved-caspase-1, and N-GSDMD, while increasing NRF2 expression. In vitro, IA enhanced granulosa cell (GC) viability, reduced reactive oxygen species (ROS), and decreased pyroptosis in LPS-treated GCs. Additionally, the beneficial effects of IA were mediated via the NRF2 pathway, as NRF2 inhibition (ML385) reversed these improvements. Additionally, we identified GSDMD as a downstream target of IA, with inhibition of GSDMD ameliorating DOR progression and inflammatory responses. CONCLUSION IA alleviates LPS-induced DOR by reducing inflammation, oxidative stress, and pyroptosis through activation of the NRF2 signaling and direct inhibition of the GSDMD pathway. These findings suggest that IA may serve as a potential therapeutic agent for improving ovarian reserve and fertility.
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Affiliation(s)
- Ling Yang
- Department of Obstetrics and Gynecology, the Hexian People's Hospital, Maanshan 238200, Anhui, China
| | - Wenya Mo
- School of Nursing, Anhui Medical University, Hefei 230032, Anhui, China; Department of Urology, the First Affiliated Hospital of University of Science and Technology of China, Hefei 230036, Anhui, China
| | - Lei Xin
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, Anhui, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, Hefei 230032, Anhui, China
| | - Mingzhao Zhang
- Department of Breast Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China
| | - Kegong Chen
- Department of Thoracic Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China
| | - Xiaohui Guo
- Department of Pathology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
| | - Jing Zhang
- College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China.
| | - Biao Yu
- Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, Anhui, China; Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, Hefei 230032, Anhui, China.
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Pang Z. Copper metabolism in hepatocellular carcinoma: from molecular mechanisms to therapeutic opportunities. Front Mol Biosci 2025; 12:1578693. [PMID: 40433591 PMCID: PMC12106024 DOI: 10.3389/fmolb.2025.1578693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Accepted: 04/17/2025] [Indexed: 05/29/2025] Open
Abstract
Copper is a vital trace metal that facilitates cell proliferation, angiogenesis, and tumour spread. The liver is essential for copper metabolism, hence regulating copper levels is crucial for hepatic health. Hepatocellular carcinoma is a primary liver cancer characterised by a high death rate, and extensive research has shown the substantial impact of copper on its progression. This research primarily examines the molecular mechanisms involved, summarises the regulation of copper homeostasis, and addresses the role of copper metabolism in the promotion and inhibition of hepatocellular carcinoma development. Furthermore, it investigates prospective clinical approaches for targeting copper in the treatment of this disease, intending to establish a theoretical basis for the clinical use of copper in the management of hepatocellular carcinoma.
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Affiliation(s)
- Ziling Pang
- Department of Nursing, School of Medicine, Shihezi University, Shihezi, China
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Khalil M, Hamadah O, Saifo M. Effect of Photobiomodulation on Salivary Nitrite in Patients with Chemotherapy-Induced Oral Mucositis: A Randomized Clinical Trial. Photobiomodul Photomed Laser Surg 2025. [PMID: 40340568 DOI: 10.1089/photob.2024.0151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2025] Open
Abstract
Background: Oral mucositis (OM) is a severe inflammatory and ulcerative condition of the oral mucosa commonly induced by chemotherapy. Photobiomodulation (PBM) therapy has been proposed for preventing and treating OM. However, the understanding of light interaction with biological tissues and the variability in light sources and protocols limit its widespread application. This study aimed to evaluate the impact of PBM on salivary nitrite levels, a marker of oxidative stress associated with inflammation and tissue damage. Materials and Methods: This prospective, randomized, double-blind clinical trial included 45 patients, evenly divided into three age- and sex-matched groups. Group 1 received basic oral care instructions prior to chemotherapy. Group 2 received these instructions plus PBM using a 650 nm intraoral diode laser. Group 3 received basic oral care instructions combined with PBM using both a 650 nm intraoral diode laser and a 980 nm extraoral diode laser. OM severity was assessed using World Health Organization criteria, and salivary nitrite levels were measured using the Griess reagent kit (Biotium®) according to the manufacturer's instructions 1 and 2 weeks after the first chemotherapy session. Results: Our study included 45 patients who were evenly distributed into three groups, matched for age, sex, tumor type, and type of chemotherapy. Significant differences in OM severity were observed among the groups at both 1 and 2 weeks (p = 0.000). Salivary nitrite levels also showed significant differences between groups at these time points (p = 0.00). Significant differences were found between the control group and both laser treatment groups, but no significant difference was noted between the two laser treatment groups. Conclusions: PBM effectively reduces OM severity, whether used intraorally alone or combined with extraoral application. This effect is likely due to PBM's ability to lower salivary nitrite levels, indicating reduced oxidative stress and inflammation.
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Affiliation(s)
- Marwa Khalil
- Department of Oral Medicine, Faculty of Dental Medicine, Damascus University, Damascus, Syria
| | - Omar Hamadah
- Department of Oral Medicine, Faculty of Dental Medicine, Damascus University, Damascus, Syria
- The Higher Institute for Laser Research and Applications, Damascus University, Damascus, Syria
| | - Maher Saifo
- Faculty of Medicine, Medical Oncology, Damascus University, Damascus, Syria
- Albairouni University Hospital, Damascus University, Damascus, Syria
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Zuo Q, Wu RB, Sun LN, Ren TY, Fan Z, Wang LY, Tan B, Luo B, Irfan M, Huang Q, Shen YJ, Zhang ZS. Genomic and Methylomic Signatures Associated With the Maintenance of Genome Stability and Adaptive Evolution in Two Closely Allied Wolf Spiders. Mol Ecol Resour 2025; 25:e14071. [PMID: 39831349 DOI: 10.1111/1755-0998.14071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 01/02/2025] [Accepted: 01/07/2025] [Indexed: 01/22/2025]
Abstract
Pardosa spiders, belonging to the wolf spider family Lycosidae, play a vital role in maintaining the health of forest and agricultural ecosystems due to their function in pest control. This study presents chromosome-level genome assemblies for two allied Pardosa species, P. laura and P. agraria. Both species' genomes show a notable expansion of helitron transposable elements, which contributes to their large genome sizes. Methylome analysis indicates that P. laura has higher overall DNA methylation levels compared to P. agraria. DNA methylation may not only aids in transposable element-driven genome expansion but also positively affects the three-dimensional organisation of P. laura after transposon amplification, thereby potentially enhancing genome stability. Genes associated with hyper-differentially methylated regions in P. laura (compared to P. agraria) are enriched in functions related to mRNA processing and energy production. Furthermore, combined transcriptome and methylome profiling has uncovered a complex regulatory interplay between DNA methylation and gene expression, emphasising the important role of gene body methylation in the regulation of gene expression. Comparative genomic analysis shows a significant expansion of cuticle protein and detoxification-related gene families in P. laura, which may improve its adaptability to various habitats. This study provides essential genomic and methylomic insights, offering a deeper understanding of the relationship between transposable elements and genome stability, and illuminating the adaptive evolution and species differentiation among allied spiders.
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Affiliation(s)
- Qing Zuo
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Run-Biao Wu
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Li-Na Sun
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Tian-Yu Ren
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Zheng Fan
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Lu-Yu Wang
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Bing Tan
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Bin Luo
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Muhammad Irfan
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Qian Huang
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
| | - Yan-Jun Shen
- Laboratory of Water Ecological Health and Environmental Safety, School of Life Sciences, Chongqing Normal University, Chongqing, China
| | - Zhi-Sheng Zhang
- Key Laboratory of Eco-Environments in Three Gorges Reservoir Region (Ministry of Education), School of Life Sciences, Southwest University, Chongqing, China
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Jing L, Zhao Y, Jiang L, Song F, An L, Qi E, Fu X, Chen J, Ma J. Unlocking the Potential of Curcumae Rhizoma Aqueous Extract in Stress Resistance and Extending Lifespan in Caenorhabditis elegans. Molecules 2025; 30:1668. [PMID: 40333562 PMCID: PMC12029441 DOI: 10.3390/molecules30081668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/27/2025] [Accepted: 04/03/2025] [Indexed: 05/09/2025] Open
Abstract
The enhancement of stress resistance is crucial for delaying aging and extending a healthy lifespan. Traditional Chinese medicine (TCM), a cherished treasure of Chinese heritage, has shown potential in mitigating stress and promoting longevity. This study integrates network pharmacology and in vivo analysis to investigate the mechanisms and effects of Curcumae Rhizoma (C. Rhizoma), known as "E Zhu" in Chinese. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) identified 10 active compounds in its aqueous extract, interacting with 128 stress-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed pathways such as stress response, FoxO signaling, and insulin resistance. In Caenorhabditis elegans, 10 mg/mL of C. Rhizoma aqueous extract improved resistance to UV, thermal, oxidative, and pathogen-induced stress, extending lifespan in a dose-dependent manner. Mechanistically, it reduced reactive oxygen species (ROS), increased superoxide dismutase (SOD) activity, and enhanced UV resistance via the insulin/IGF-1 pathway and DAF-16 translocation. Molecular docking highlighted hexahydrocurcumin (HHC) and related compounds as key bioactives. Furthermore, we also observed that C. Rhizoma aqueous extract significantly extended both the lifespan and healthspan of nematodes. These findings highlight the potential of C. Rhizoma in stress mitigation and longevity promotion, offering valuable insights into the therapeutic applications of TCM.
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Affiliation(s)
- Linyao Jing
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China; (L.J.); (Y.Z.); (F.S.); (L.A.); (E.Q.); (X.F.)
| | - Yanlin Zhao
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China; (L.J.); (Y.Z.); (F.S.); (L.A.); (E.Q.); (X.F.)
| | - Lijun Jiang
- Changchun Heber Biological Technology Co., Ltd., Changchun 130012, China;
| | - Fei Song
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China; (L.J.); (Y.Z.); (F.S.); (L.A.); (E.Q.); (X.F.)
| | - Lu An
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China; (L.J.); (Y.Z.); (F.S.); (L.A.); (E.Q.); (X.F.)
| | - Edmund Qi
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China; (L.J.); (Y.Z.); (F.S.); (L.A.); (E.Q.); (X.F.)
| | - Xueqi Fu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China; (L.J.); (Y.Z.); (F.S.); (L.A.); (E.Q.); (X.F.)
| | - Jing Chen
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China; (L.J.); (Y.Z.); (F.S.); (L.A.); (E.Q.); (X.F.)
| | - Junfeng Ma
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China; (L.J.); (Y.Z.); (F.S.); (L.A.); (E.Q.); (X.F.)
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Das S, Thakur S, Cahais V, Virard F, Claeys L, Renard C, Cuenin C, Cros MP, Keïta S, Venuti A, Sirand C, Ghantous A, Herceg Z, Korenjak M, Zavadil J. Molecular and cell phenotype programs in oral epithelial cells directed by co-exposure to arsenic and smokeless tobacco. Biofactors 2025; 51:e70011. [PMID: 40056068 PMCID: PMC11962598 DOI: 10.1002/biof.70011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 02/26/2025] [Indexed: 04/04/2025]
Abstract
Chronic exposure to arsenic can lead to various health issues, including cancer. Concerns have been mounting about the enhancement of arsenic toxicity through co-exposure to various prevalent lifestyle habits. Smokeless tobacco (SLT) products are commonly consumed in South Asian countries, where their use frequently co-occurs with exposure to arsenic from contaminated groundwater. To decipher the in vitro molecular and cellular responses to arsenic and/or smokeless tobacco, we performed temporal multi-omics analysis of the transcriptome and DNA methylome remodeling in exposed hTERT-immortalized human normal oral keratinocytes (NOK), as well as arsenic and/or smokeless tobacco genotoxicity and mutagenicity investigations in NOK cells and in human p53 knock-in murine embryonic fibroblasts (Hupki MEF). RNAseq results from acute exposures of NOK cell to arsenic alone and in combination with smokeless tobacco extract revealed upregulation of genes with roles in cell cycle changes, apoptosis and inflammatory responses. This was in keeping with global DNA hypomethylation affecting genes involved in the same processes after chronic treatment. At the phenotypic level, we observed a dose-dependent decrease in NOK cell viability, induction of DNA damage, cell cycle changes and increased apoptosis, with the most pronounced effects observed under arsenic and SLT co-exposure conditions. Live-cell imaging experiments indicated that the DNA damage likely resulted from induction of apoptosis, an observation validated by a lack of exome-wide mutagenesis in response to chronic exposure to arsenic and/or smokeless tobacco. In sum, our integrative omics study provides novel insights into the acute and chronic responses to arsenic and smokeless tobacco (co-)exposure, with both types of responses converging on several key mechanisms associated with cancer hallmark processes. The resulting rich catalogue of molecular programs in oral cells regulated by arsenic and smokeless tobacco (co-)exposure may provide bases for future development of biomarkers for use in molecular cancer epidemiology studies of exposed populations at risk.
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Affiliation(s)
- Samrat Das
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Shefali Thakur
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK
| | - Vincent Cahais
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - François Virard
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
- University Claude Bernard Lyon 1, INSERM U1052–CNRS UMR5286, Cancer Research Center, Centre Léon Bérard, Lyon, France
- University of Lyon, Faculty of Odontology, Hospices Civils de Lyon, Lyon, France
| | - Liesel Claeys
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
- Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
| | - Claire Renard
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Cyrille Cuenin
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Marie-Pierre Cros
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Stéphane Keïta
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Assunta Venuti
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Cécilia Sirand
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Akram Ghantous
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Zdenko Herceg
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Michael Korenjak
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Jiri Zavadil
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
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Liu B, Peng B, Jin Y, Tao Y, Xu W, Zhang Y, Li Z. Developmental Toxicity and Cardiotoxicity of N, N-Dimethylaniline in Zebrafish Embryos. TOXICS 2025; 13:125. [PMID: 39997940 PMCID: PMC11860635 DOI: 10.3390/toxics13020125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 01/26/2025] [Accepted: 01/30/2025] [Indexed: 02/26/2025]
Abstract
N, N-Dimethylaniline is an important chemical intermediate and an important metabolite of the pesticide Fenaminosulf. It is widely used in chemical production, but there is an extreme paucity of environmental risk assessments for N, N-dimethylaniline.: In this study, the cardiotoxicity of continuous exposure to N, N-dimethylaniline (20, 40, and 80 μg/mL) for 72 h was evaluated using zebrafish embryos.: The study found that N, N-dimethylaniline not only exhibits developmental toxicity to zebrafish embryos, leading to abnormalities such as pericardial edema, yolk sac edema, and spinal curvature, but also induces oxidative stress, lipid accumulation, and apoptosis, particularly affecting the heart region. Cardiac function indicators such as pericardial area, sinus venosus (SV) and bulbar artery (BA) distance, heart rate, and red blood cell (RBC) rate were all significantly altered due to exposure to N, N-dimethylaniline, with impaired cardiac morphology and structure and the downregulation of gene expression related to heart development and function (myl7, vmhc, myh6, bmp4, tbx2b, and has2).: The research findings suggest that the heart may be the potential target organ for the toxic effects of N, N-dimethylaniline, providing a scientific basis for the rational use of this compound and environmental protection. Furthermore, it enhances public awareness of the safety of substances that may degrade to produce N, N-dimethylaniline during their use.
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Affiliation(s)
- Bin Liu
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (B.L.); (B.P.); (Y.T.); (W.X.)
- Qingpu District Agro-Technology Extension Service Center, Shanghai 201799, China;
| | - Bo Peng
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (B.L.); (B.P.); (Y.T.); (W.X.)
| | - Yan Jin
- Qingpu District Agro-Technology Extension Service Center, Shanghai 201799, China;
| | - Yijie Tao
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (B.L.); (B.P.); (Y.T.); (W.X.)
| | - Wenping Xu
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (B.L.); (B.P.); (Y.T.); (W.X.)
| | - Yang Zhang
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (B.L.); (B.P.); (Y.T.); (W.X.)
| | - Zhong Li
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (B.L.); (B.P.); (Y.T.); (W.X.)
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Zhao J, He C, Xie H, Zou Y, Yan Z, Deng J, Du Y, Yang W, Zhang X. Latent Association Between Diets and Glioma Risk: A Mendelian Randomization Analysis. Nutrients 2025; 17:582. [PMID: 39940440 PMCID: PMC11819737 DOI: 10.3390/nu17030582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/03/2025] [Accepted: 02/04/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Gliomas, particularly high-grade gliomas such as glioblastoma, represent a major challenge due to their poor prognosis. While dietary factors have been proposed as potential modulators of glioma risk, causal inference has been hindered by confounding and reverse causality in observational studies. This study employs Mendelian randomization to investigate the causal relationship between dietary factors and glioma risk. METHODS A two-sample MR framework was applied, utilizing genome-wide association study data for 22 dietary exposures and glioma risks, including both GBM and non-GBM subtypes. Instrumental variables (genetic variants) were identified for each dietary factor to address confounding and pleiotropy. Causal inference was conducted using inverse-variance weighted regression, complemented by MR-Egger and MR-PRESSO analyses to assess and correct for potential pleiotropy. RESULTS A positive causal association was observed between the intake of cooked vegetables and the GBM risk (OR = 6.55, 95% CI: 1.86-23.12, p = 0.00350). While alcohol intake demonstrated a protective effect for non-GBM risk (OR = 0.770, 95% CI: 0.61-0.97, p = 0.029), beer was substantially linked to an increased risk of non-GBM gliomas (OR = 4.82, 95% CI: 1.84-12.59, p = 0.0014). Other dietary factors did not exhibit significant causal associations. CONCLUSIONS These findings suggest that certain dietary factors, including cooked vegetable intake, beer consumption, and alcohol intake, may exert a causal influence on glioma risk. This study provides new insights into the potential dietary determinants of glioma and underscores the need for further investigation into modifiable risk factors for glioma prevention.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xiangheng Zhang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China; (J.Z.); (C.H.); (H.X.); (Y.Z.); (Z.Y.); (J.D.); (Y.D.); (W.Y.)
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Dai C, Liu D, Qin C, Fang J, Cheng G, Xu C, Wang Q, Lu T, Guo Z, Wang J, Zhong T, Guo Q. Guben Kechuan granule attenuates bronchial asthma by inhibiting NF-κB/STAT3 signaling pathway-mediated apoptosis. JOURNAL OF ETHNOPHARMACOLOGY 2025; 340:119124. [PMID: 39694430 DOI: 10.1016/j.jep.2024.119124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 10/20/2024] [Accepted: 11/15/2024] [Indexed: 12/20/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chronic asthma caused by allergies is a lung illness marked by airway remodeling and hyperresponsiveness. Guben Kechuan (GK) granule is a clinically proven formula for treating lung disease. It relieves cough and helps to clear phlegm, but the mechanisms underlying its treatment for asthma are not clear. AIM OF THE STUDY We aimed to elucidate the efficacy and potential mechanisms by which GK ameliorates allergic asthma. MATERIALS AND METHODS Ultra-performance liquid chromatography (UHPLC-LTQ-Orbitrap-MS) identified the main chemical components of GK. The efficacy of GK was studied in an ovalbumin/alum (OVA)/AL(OH)3-sensitized rat model of bronchial asthma by measuring cytokine concentrations in serum and alveolar lavage samples, examining tissue pathology, and performing leukocyte counts. The mechanisms underlying its effectiveness in asthma were investigated by both transcriptomic and proteomic analyses. RESULTS GK relieved asthma-induced airway inflammation and remodeling, reduced inflammatory cell infiltration, and decreased the levels of the inflammatory cytokines TNF-α, IL-4, IL-5, IL-6, and IL-10. Analysis of the transcriptomic and proteomic results found that asthma activated the transcription factors STAT3 and NF-κB and induced oxidative-stress damage and apoptosis. GK was found to reduce Bax and caspase-3 expression, increase Bcl-2 expression, and inhibit asthma-induced apoptosis. GK downregulated the expression of the transcription factors STAT3 and NF-kB, which decreased the inflammatory response. Decreases in CAT, SOD, and GSH reduced asthma-induced oxidative-stress damage. CONCLUSIONS Our findings provide evidence that GK alleviates bronchial asthma by inhibiting apoptosis and oxidative stress damage mediated by the NF-κB/STAT3 signaling pathway.
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Affiliation(s)
- Chuanhao Dai
- Department of Clinical Laboratory, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China
| | - Dewen Liu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Cuiying Qin
- Development Center of Medical Science & Technology National Health Commission of the People's Republic of China, Beijing, 100044, China
| | - Jingya Fang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Guangqing Cheng
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Chunhong Xu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Qixin Wang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Tianming Lu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Zuchang Guo
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Jigang Wang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China; Department of Critical Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518020, China.
| | - Tianyu Zhong
- Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China.
| | - Qiuyan Guo
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
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Čakar U, Čolović M, Milenković D, Pagnacco M, Maksimović J, Krstić D, Đorđević B. Strawberry and Drupe Fruit Wines Antioxidant Activity and Protective Effect Against Induced Oxidative Stress in Rat Synaptosomes. Antioxidants (Basel) 2025; 14:155. [PMID: 40002342 PMCID: PMC11851380 DOI: 10.3390/antiox14020155] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/27/2025] Open
Abstract
The aim of this study was to investigate the antioxidant capacity of fruit wines and their protective effects against hydrogen peroxide-induced oxidative stress in rat synaptosomes in vitro. The wines were produced from strawberries and drupe fruits (i.e., plum, sweet cherry, peach, and apricot) through microvinification with a pure S. cerevisiae yeast culture. Fruit wines were produced with and without added sugar before the start of fermentation, whereas subvariants with and without pits were only applied to drupe fruit wines. First, synaptosomes were treated with the wines, while oxidative stress was induced with H2O2. Subsequently, the activities of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)) and the content of malondialdehyde (MDA), an indicator of membrane injury, were determined. In addition, the Briggs-Rauscher reaction (BR) was used to evaluate the inhibition capacity against free radicals. All investigated fruit wines increased the activity of the studied antioxidant enzymes and decreased MDA content compared to the corresponding controls (synaptosomes treated with H2O2). After synaptosomal treatment with plum wine, the highest activities were observed for SOD (5.57 U/mg protein) and GPx (0.015 U/mg protein). Strawberry wine induced the highest CAT activity (0.047 U/mg protein) and showed the best ability to reduce lipid peroxidation, yielding the lowest MDA level (2.68 nmol/mg). Strawberry, plum, and sweet cherry wines were identified as samples with higher antioxidant activity in both principal component analysis (PCA) and hierarchical cluster analysis (HCA). Finally, plum wine exhibited the highest inhibitory activity in the BR reaction (397 s). The results suggest that fruit wines could be considered potential functional food due to their protective effects against oxidative stress.
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Affiliation(s)
- Uroš Čakar
- Department of Bromatology, Faculty of Pharmacy, University of Belgrade, 11 000 Belgrade, Serbia;
| | - Mirjana Čolović
- Department of Physical Chemistry, “Vinča” Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, 11 351 Belgrade, Serbia;
| | - Danijela Milenković
- Department of Physics and Mathematics, Faculty of Pharmacy, University of Belgrade, 11 000 Belgrade, Serbia;
| | - Maja Pagnacco
- Department of Catalysis and Chemical Engineering, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, 11 000 Belgrade, Serbia;
| | - Jelena Maksimović
- Faculty of Physical Chemistry, University of Belgrade, 11 158 Belgrade, Serbia;
| | - Danijela Krstić
- Institute of Medical Chemistry, Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia;
| | - Brižita Đorđević
- Department of Bromatology, Faculty of Pharmacy, University of Belgrade, 11 000 Belgrade, Serbia;
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11
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Kwon YS, Park CB, Lee SM, Park JW, Kim YJ, Kim JH, Seo JS. Comprehensive analysis of proteomic and biochemical responses of Daphnia magna to short-term exposure to polystyrene microplastic particles. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 290:117581. [PMID: 39729941 DOI: 10.1016/j.ecoenv.2024.117581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/18/2024] [Accepted: 12/18/2024] [Indexed: 12/29/2024]
Abstract
Microplastic (MP) represent a pervasive and escalating threat to aquatic ecosystems, impacting organisms from cellular to population levels. To investigate the immediate molecular impacts of MP exposure, we exposed Daphnia magna, a keystone species in freshwater ecosystems, to polystyrene microplastic particles (5 μm, 5 μg/L) for 48 h. Through proteomic and biochemical analyses, we identified extensive disruptions in key physiological pathways. Notably, proteins involved in energy metabolism, including glycolysis and the tricarboxylic acid (TCA) cycle, were downregulated, suggesting a metabolic shift away from growth-related processes. Elevated levels of oxidative stress markers such as superoxide dismutase, catalase, and glutathione reductase reflected a pronounced response to reactive oxygen species. The upregulation of endocytosis-related proteins, including caveolin-1 (CAV1) and phosphatidylinositol-4-phosphate 5-kinase (PIP5K), highlights their role in actively internalizing and compartmentalizing MP, potentially as a protective mechanism against oxidative damage. These findings reveal that short-term MP exposure triggers a complex, multi-pathway stress response in D. magna, underscoring potential vulnerabilities that could impact broader ecological dynamics. This study emphasizes the urgency of understanding MP toxicity to guide environmental policies and conservation efforts aimed at mitigating the effects of plastic pollution.
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Affiliation(s)
- Young Sang Kwon
- Center for Environmental Safety Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of Korea
| | - Chang-Beom Park
- Center for Ecotoxicology and Environmental Future Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of Korea
| | - Seung-Min Lee
- Center for Environmental Safety Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of Korea
| | - Jin-Woo Park
- Center for Environmental Safety Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of Korea
| | - Yeong-Jin Kim
- Center for Environmental Safety Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of Korea
| | - Jong-Hwan Kim
- Center for Environmental Safety Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of Korea
| | - Jong-Su Seo
- Center for Environmental Safety Research, Division of Gyeongnam Bio-Environmental Research, Korea Institute of Toxicology, Jinju 52834, Republic of Korea.
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12
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Nandha SR, Checker R, Patwardhan RS, Sharma D, Sandur SK. Anti-oxidants as therapeutic agents for oxidative stress associated pathologies: future challenges and opportunities. Free Radic Res 2025; 59:61-85. [PMID: 39764687 DOI: 10.1080/10715762.2025.2450504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 12/13/2024] [Accepted: 12/31/2024] [Indexed: 01/11/2025]
Abstract
Free radicals have been implicated in the pathogenesis of cancer along with cardiovascular, neurodegenerative, pulmonary and inflammatory disorders. Further, the relationship between oxidative stress and disease is distinctively established. Clinical trials using anti-oxidants for the prevention of disease progression have indicated some beneficial effects. However, these trials failed to establish anti-oxidants as therapeutic agents due to lack of efficacy. This is attributed to the fact that living systems are under dynamic redox control wherein their redox behavior is compartmentalized and simple aggregation of redox couples, distributed throughout the system, is of miniscule importance while determining their overall redox state. Further, free radical metabolism is intriguingly complex as they play plural roles segregated in a spatio-temporal manner. Depending on quality, quantity and site of generation, free radicals exhibit beneficial or harmful effects. Use of nonspecific, non-targeted, general ROS scavengers lead to systemic elimination of all types of ROS and interferes in cellular signaling. Failure of anti-oxidants to act as therapeutic agents lies in this oversimplification of extremely dynamic cellular redox environment as a static and non-compartmentalized redox state. Rather than generalizing the term "oxidative stress" if we can identify the "type of oxidative stress" in different types of diseases, a targeted and more specific anti-oxidant therapy may be developed. In this review, we discuss the concept of redox dynamics, role and type of oxidative stress in disease conditions, and current status of anti-oxidants as therapeutic agents. Further, we probe the possibility of developing novel, targeted and efficacious anti-oxidants with drug-like properties.
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Affiliation(s)
- Shivani R Nandha
- Radiation Biology & Health Sciences Division, Bio-science Group, Bhabha Atomic Research Centre, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Rahul Checker
- Radiation Biology & Health Sciences Division, Bio-science Group, Bhabha Atomic Research Centre, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Raghavendra S Patwardhan
- Radiation Biology & Health Sciences Division, Bio-science Group, Bhabha Atomic Research Centre, Mumbai, India
| | - Deepak Sharma
- Radiation Biology & Health Sciences Division, Bio-science Group, Bhabha Atomic Research Centre, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Santosh K Sandur
- Radiation Biology & Health Sciences Division, Bio-science Group, Bhabha Atomic Research Centre, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
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13
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Fang F, Zhu Y, Xu W, Zhang Y, Cheng J. Insights into the developmental and cardiovascular toxicity of bixafen using zebrafish embryos and larvae. ENVIRONMENTAL RESEARCH 2024; 262:119916. [PMID: 39233032 DOI: 10.1016/j.envres.2024.119916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 08/06/2024] [Accepted: 09/01/2024] [Indexed: 09/06/2024]
Abstract
Bixafen (BIX), a member of the succinate dehydrogenase inhibitor (SDHI) class of fungicides, has seen a surge in interest due to its expanding market presence and positive development outlook. However, there is a growing concern about its potential harm to aquatic life, largely due to its resistance to breaking down in the environment. In this study, we thoroughly examined the toxicological impact of BIX on zebrafish as a model organism. Our results revealed that BIX significantly hindered the development of zebrafish embryos, leading to increased mortality, hatching failures, and oxidative stress. Additionally, we observed cardiovascular abnormalities, including dilated cardiac chambers, reduced heart rate, sluggish blood circulation, and impaired vascular function. Notably, BIX also altered the expression of key genes involved in cardiovascular development, such as myl7, vmhc, nkx2.5, tbx5, and flt1. In summary, BIX was found to induce developmental and cardiovascular toxicity in zebrafish, underscoring the risks associated with SDHI pesticides and emphasizing the need for a reassessment of their impact on human health. These findings are crucial for the responsible use of BIX.
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Affiliation(s)
- Fei Fang
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China
| | - Yanjuan Zhu
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China
| | - Wenping Xu
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China
| | - Yang Zhang
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
| | - Jiagao Cheng
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
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14
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Shirmard LR, Khezri S, Ahadzadeh S, Azadimoghaddam P, Azizian S, Salimi A. Preparation of gallic acid-loaded chitosan nanoparticles and their chemoprotective effects on N-ethyl-N-nitrosourea-induced hepatotoxicity and mortality in rats. J Mol Histol 2024; 56:1. [PMID: 39585491 DOI: 10.1007/s10735-024-10280-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 11/05/2024] [Indexed: 11/26/2024]
Abstract
N-ethyl-N-nitrosourea (ENU) as n-nitrosamine and alkylating agent, ubiquitous within living cells and in the environment can act as a full carcinogen and induce tumor formation in various tissues such as liver. In this study, gallic acid-loaded chitosan nanoparticles (GANPs) were synthesized and evaluated for their chemopreventive effect against ENU-induced hepatotoxicity and mortality in rats. Twenty-four male Wistar rats were divided into four groups including: control, ENU (single doses of 50 mg/kg via intraperitoneal injection), GA + ENU and GANPs + ENU. Animals were orally pretreated with GA (50 mg/kg) and GANPs (50 mg/kg) for 30 days, and liver injuries induced by ENU on the 31st day of study. After ENU administration, weight changes and mortality were monitored during 30 days, and then the animals were sacrificed and alpha-fetoprotein (AFP) as a tumor marker, liver function tests (ALT, AST and ALP), oxidative stress markers (GSH and MDA), mitochondrial toxicity parameters, and histopathological assessment were evaluated. Except for AFP and MDA, ENU caused significant elevation of liver enzymes, mitochondrial ROS formation, collapse of mitochondrial membrane potential depletion of GSH, histopathological abnormalities and mortality in rats. Our data showed that GANPs significantly increased the survival of rats by up to 66%, delayed in death time and prevented weight changes after exposure to ENU. Moreover, GANPs restored liver enzyme levels, ROS formation, mitochondrial dysfunction, GSH levels, and histopathological abnormalities towards normal. Our findings suggest that GANPs revealed a significant protective effect against deadly toxicity induced by ENU as an alkylating full carcinogen agent in liver tissue.
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Affiliation(s)
- Leila Rezaie Shirmard
- Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Saleh Khezri
- Department of Pharmacology and Toxicology, Associate Professor of Toxicology and Pharmacology School of Pharmacy, Ardabil University of Medical Sciences, P.O. Box: 56189-53141, Ardabil, Iran
| | - Sara Ahadzadeh
- Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Paniiiz Azadimoghaddam
- Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Sepideh Azizian
- Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Ahmad Salimi
- Department of Pharmacology and Toxicology, Associate Professor of Toxicology and Pharmacology School of Pharmacy, Ardabil University of Medical Sciences, P.O. Box: 56189-53141, Ardabil, Iran.
- Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
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15
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Gao S, Shan Y, Wang Y, Wang W, Li J, Tan H. Polysaccharides from Lonicera japonica Thunb.: Extraction, purification, structural features and biological activities-A review. Int J Biol Macromol 2024; 281:136472. [PMID: 39414197 DOI: 10.1016/j.ijbiomac.2024.136472] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 09/13/2024] [Accepted: 10/08/2024] [Indexed: 10/18/2024]
Abstract
Lonicera japonica Thunb.,commonly referred to as Caprifolium japonicum (Thunb.) Dum. Cours.,is a perennial herb classified under the caprifoliaceae family. It is utilized worldwide as a medicinal plant and also serves as food source and an ornamental plant. Lonicera japonica Thunb. polysaccharides (LJP) constitute one of its primary components, demonstrating a wide range of biological activities including anti-inflammatory, antioxidant, immunomodulatory, anti-Alzheimer's, anti-diabetic, and anti-cancer effects. This paper reviews and summarizes recent research advancements on the extraction, purification, structural characteristics, and biological activities of LJP, offering a valuable foundation and up-to-date insights for the continued development and application of LJP in pharmaceutical and functional food sectors.
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Affiliation(s)
- Shiyong Gao
- Drug Engineering and Technology Research Center, Harbin University of Commerce, Harbin 150076, China; Heilongjiang Provincial Key Laboratory of Tumor Prevention and Antitumor Drugs, Harbin 150076, China
| | - Yanmin Shan
- Drug Engineering and Technology Research Center, Harbin University of Commerce, Harbin 150076, China; Heilongjiang Provincial Key Laboratory of Tumor Prevention and Antitumor Drugs, Harbin 150076, China
| | - Yue Wang
- Drug Engineering and Technology Research Center, Harbin University of Commerce, Harbin 150076, China; Heilongjiang Provincial Key Laboratory of Tumor Prevention and Antitumor Drugs, Harbin 150076, China
| | - Weiya Wang
- Drug Engineering and Technology Research Center, Harbin University of Commerce, Harbin 150076, China; Heilongjiang Provincial Key Laboratory of Tumor Prevention and Antitumor Drugs, Harbin 150076, China
| | - Jianwen Li
- Drug Engineering and Technology Research Center, Harbin University of Commerce, Harbin 150076, China; Heilongjiang Provincial Key Laboratory of Tumor Prevention and Antitumor Drugs, Harbin 150076, China
| | - Huixin Tan
- Department of pharmacy, Fourth Affiliated Hospital of Harbin Medicine University, Harbin 150001, China.
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16
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Pi X, Liu C, Jia X, Zhang Y, Liu J, Wang B, Wang L, Li Z, Ren A, Jin L. Periconceptional polycyclic aromatic hydrocarbon levels in maternal hair and fetal risk for congenital heart defects. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 286:117251. [PMID: 39490106 DOI: 10.1016/j.ecoenv.2024.117251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 10/22/2024] [Accepted: 10/23/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND Congenital heart defects (CHDs) have a complex etiology, and environmental factors play an important role in their occurrence. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous chemicals, and some have teratogenic potential. However, few studies have examined PAHs exposure and CHD risk. We investigated the association between PAHs in maternal scalp hair and CHD risk. METHODS A case-control study involving 170 severe CHD cases and 170 healthy controls was conducted, and the concentrations of 11 PAHs in maternal hair grown during the periconceptional period were quantified. A generalized linear mixed model (GLMM) was used to determine the effects of each PAHs on the risk for CHDs. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to assess the overall effects of the 11-PAHs mixture on the risk for CHDs. RESULTS The median concentration of chrysene (CHR) was higher in CHD cases (9.75 ng/g) than in controls (6.50 ng/g). In GLMM, higher levels of CHR were associated with a 4.88-fold greater risk for CHDs (95 % confidence interval [CI]: 2.69-8.89). In WQS regression, higher levels of PAHs mixture were associated with a 2.03-fold greater CHD risk (95 % CI: 1.75-2.31), and CHR had the highest weighting (weighted 0.9346). In BKMR, CHD risks increased steadily with the levels of the PAHs mixture. CHR showed a toxic effect when the other PAHs were fixed at their 25th, 50th, or 75th percentile. No interactions among PAHs were found. CONCLUSIONS When examined individually, a high concentration of CHR in periconceptional maternal hair was associated with an increased risk for CHDs. When considering the 11 PAHs together, higher levels of the PAHs mixture were associated with increased odds of CHD occurrence.
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Affiliation(s)
- Xin Pi
- Department of Social Medicine and Health Education, School of Public Health, Peking University, Beijing, China; Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China
| | - Chunyi Liu
- Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Xiaoqian Jia
- Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Yali Zhang
- Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Jufen Liu
- Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Bin Wang
- Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Linlin Wang
- Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Zhiwen Li
- Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
| | - Aiguo Ren
- Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Lei Jin
- Institute of Reproductive and Child Health/ National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
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17
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Das S, Thakur S, Cahais V, Virard F, Claeys L, Renard C, Cuenin C, Cros MP, Keïta S, Venuti A, Sirand C, Ghantous A, Herceg Z, Korenjak M, Zavadil J. Molecular and cell phenotype programs in oral epithelial cells directed by co-exposure to arsenic and smokeless tobacco. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.10.14.618077. [PMID: 39463997 PMCID: PMC11507705 DOI: 10.1101/2024.10.14.618077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
Chronic arsenic exposure can lead to various health issues, including cancer. Concerns have been mounting about the enhancement of arsenic toxicity through co-exposure to various prevalent lifestyle habits. Smokeless tobacco products are commonly consumed in South Asian countries, where their use frequently co-occurs with exposure to arsenic from contaminated groundwater. To decipher the in vitro molecular and cellular responses to arsenic and/or smokeless tobacco, we performed temporal multi-omics analysis of the transcriptome and DNA methylome remodelling in exposed hTERT-immortalized human normal oral keratinocytes (NOK), as well as arsenic and/or smokeless tobacco genotoxicity and mutagenicity investigations in NOK cells and in human p53 knock-in murine embryonic fibroblasts (Hupki MEF). RNAseq results from acute exposures to arsenic alone and in combination with smokeless tobacco extract revealed upregulation of genes with roles in cell cycle changes, apoptosis and inflammation responses. This was in keeping with global DNA hypomethylation affecting genes involved in the same processes in response to chronic treatment in NOK cells. At the phenotypic level, we observed a dose-dependent decrease in NOK cell viability, induction of DNA damage, cell cycle changes and increased apoptosis, with the most pronounced effects observed under arsenic and SLT co-exposure conditions. Live-cell imaging experiments indicated that the DNA damage likely resulted from induction of apoptosis, an observation validated by a lack of exome-wide mutagenesis in response to chronic exposure to arsenic and/or smokeless tobacco. In sum, our integrative omics study provides novel insights into the acute and chronic responses to arsenic and smokeless tobacco (co-)exposure, with both types of responses converging on several key mechanisms associated with cancer hallmark processes. The generated rich catalogue of molecular programs in oral cells regulated by arsenic and smokeless tobacco (co-)exposure may provide bases for future development of biomarkers for use in molecular epidemiology studies of exposed populations at risk of developing oral cancer.
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Affiliation(s)
- Samrat Das
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Shefali Thakur
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK
| | - Vincent Cahais
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - François Virard
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
- University Claude Bernard Lyon 1, INSERM U1052–CNRS UMR5286, Cancer Research Center, Centre Léon Bérard, Lyon, France
- University of Lyon, Faculty of Odontology, Hospices Civils de Lyon, Lyon, France
| | - Liesel Claeys
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
- Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
| | - Claire Renard
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Cyrille Cuenin
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Marie-Pierre Cros
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Stéphane Keïta
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Assunta Venuti
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Cécilia Sirand
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Akram Ghantous
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Zdenko Herceg
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Michael Korenjak
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
| | - Jiri Zavadil
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France
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18
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Klaunig JE, Cohen SM. Mode of action of dieldrin-induced liver tumors: application to human risk assessment. Crit Rev Toxicol 2024; 54:634-658. [PMID: 39077834 DOI: 10.1080/10408444.2024.2377208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 06/27/2024] [Accepted: 06/28/2024] [Indexed: 07/31/2024]
Abstract
Dieldrin is an organochlorine insecticide that was widely used until 1970 when its use was banned because of its liver carcinogenicity in mice. Several long-term rodent bioassays have reported dieldrin to induce liver tumors in in several strains of mice, but not in rats. This article reviews the available information on dieldrin liver effects and performs an analysis of mode of action (MOA) and human relevance of these liver findings. Scientific evidence strongly supports a MOA based on CAR activation, leading to alterations in gene expression, which result in increased hepatocellular proliferation, clonal expansion leading to altered hepatic foci, and ultimately the formation of hepatocellular adenomas and carcinomas. Associative events include increased liver weight, centrilobular hypertrophy, increased expression of Cyp2b10 and its resulting increased enzymatic activity. Other associative events include alterations of intercellular gap junction communication and oxidative stress. Alternative MOAs are evaluated and shown not to be related to dieldrin administration. Weight of evidence shows that dieldrin is not DNA reactive, it is not mutagenic, and it is not genotoxic in general. Furthermore, activation of other pertinent nuclear receptors, including PXR, PPARα, AhR, and estrogen are not related to dieldrin-induced liver tumors nor is there liver cytotoxicity. In previous studies, rats, dogs, and non-human primates did not show increased cell proliferation or production of pre-neoplastic or neoplastic lesions following dieldrin treatment. Thus, the evidence strongly indicates that dieldrin-induced mouse liver tumors are due to CAR activation and are specific to the mouse, which are qualitatively not relevant to human hepatocarcinogenesis. Thus, there is no carcinogenic risk to humans. This conclusion is also supported by a lack of positive epidemiologic findings for evidence of liver carcinogenicity. Based on current understanding of the mode of action of dieldrin-induced liver tumors in mice, the appropriate conclusion is that dieldrin is a mouse specific liver carcinogen and it does not pose a cancer risk to humans.
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Affiliation(s)
- James E Klaunig
- Department of Environmental and Occupational Health, Indiana University School of Public Health, Bloomington, IN, USA
| | - Samuel M Cohen
- Department of Pathology, Microbiology, and Immunology and the Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
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19
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Chen C, Guo L, Shen Y, Hu J, Gu J, Ji G. Oxidative damage and cardiotoxicity induced by 2-aminobenzothiazole in zebrafish (Danio rerio). JOURNAL OF HAZARDOUS MATERIALS 2024; 476:135032. [PMID: 38959826 DOI: 10.1016/j.jhazmat.2024.135032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 06/20/2024] [Accepted: 06/23/2024] [Indexed: 07/05/2024]
Abstract
There is limited information available on cardiovascular toxicity of 2-Aminobenzothiazole (NTH), a derivative of benzothiazole (BTH) commonly used in tire production, in aquatic organisms. In the present study, the zebrafish embryos were exposed to varying concentrations of NTH (0, 0.05, 0.5, and 5 mg/L) until adulthood and the potential cardiovascular toxicity was assessed. NTH exposure resulted in striking aberrations in cardiac development, including heart looping failure and interference with atrioventricular canal differentiation. RNA-sequencing analysis indicated that NTH causes oxidative damage to the heart via ferroptosis, leading to oxygen supply disruption, cardiac malformation, and ultimately, zebrafish death. Quantitative real-time polymerase chain reaction (qPCR) analysis demonstrated the dysregulation of genes associated with early heart development, contraction, and oxidative stress. Additionally, reactive oxygen species accumulation and glutathione/malondialdehyde levels changes suggested a potential link between cardiac developmental toxicity and oxidative stress. In adult zebrafish, NTH exposure led to ventricular enlargement, decreased heart rate, reduced blood flow, and prolonged RR, QRS, and QTc intervals. To the best of our knowledge, this study is the first to provide evidence of cardiac toxicity and the adverse effects of ontogenetic NTH exposure in zebrafish, revealing the underlying toxic mechanisms connected with oxidative stress damage. These findings may provide crucial insights into the environmental risks associated with NTH and other BTHs.
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Affiliation(s)
- Chen Chen
- Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing 210042, China; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China
| | - Liguo Guo
- Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing 210042, China
| | - Yuehong Shen
- Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing 210042, China
| | - Jun Hu
- School of Environmental Science and Engineering, Nanjing Tech University, Jiangsu 211816, China
| | - Jie Gu
- Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing 210042, China.
| | - Guixiang Ji
- Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing 210042, China.
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20
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Cornea AC, Marc G, Ionuț I, Moldovan C, Fizeșan I, Petru AE, Creștin IV, Pîrnău A, Vlase L, Oniga O. Synthesis, Cytotoxicity and Antioxidant Activity Evaluation of Some Thiazolyl-Catechol Compounds. Antioxidants (Basel) 2024; 13:937. [PMID: 39199183 PMCID: PMC11351550 DOI: 10.3390/antiox13080937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 09/01/2024] Open
Abstract
A series of thiazolyl-catechol compounds with antioxidant and cytotoxic activities were synthesized by a Hantzsch heterocyclization, using diverse thioamides as the thiocarbonyl component and 4-chloroacetyl-catechol as haloketone. These compounds were characterized by MS, IR spectroscopy, and NMR. Their antioxidant potential was evaluated by antiradical, electron transfer, and ferrous ion chelation assays using ascorbic acid, Trolox, and EDTA-Na2 as references. The cytotoxicity of the synthesized compounds was evaluated on two different cell types, normal human foreskin fibroblasts (BJ) and human pulmonary malignant cells (A549), using gefitinib as a reference anticancer drug. The results obtained from the tests highlighted compounds 3g and 3h with significant antioxidant activities. The highest cytotoxic potency against A549 cells was exhibited by compounds 3i and 3j, while compound 3g demonstrated exceptional selectivity on malignant cells compared to gefitinib. These promising results encourage further investigation into targeted modifications on position 2 of the thiazole ring, in order to develop novel therapeutic agents.
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Affiliation(s)
- Alexandra Cătălina Cornea
- Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania; (A.C.C.); (I.I.); (C.M.); (O.O.)
| | - Gabriel Marc
- Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania; (A.C.C.); (I.I.); (C.M.); (O.O.)
| | - Ioana Ionuț
- Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania; (A.C.C.); (I.I.); (C.M.); (O.O.)
| | - Cristina Moldovan
- Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania; (A.C.C.); (I.I.); (C.M.); (O.O.)
| | - Ionel Fizeșan
- Department of Toxicology, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 8 Victor Babeș, 400012 Cluj-Napoca, Romania; (A.-E.P.); (I.-V.C.)
| | - Andreea-Elena Petru
- Department of Toxicology, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 8 Victor Babeș, 400012 Cluj-Napoca, Romania; (A.-E.P.); (I.-V.C.)
| | - Ionuț-Valentin Creștin
- Department of Toxicology, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 8 Victor Babeș, 400012 Cluj-Napoca, Romania; (A.-E.P.); (I.-V.C.)
| | - Adrian Pîrnău
- National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath Street, 400293 Cluj-Napoca, Romania;
| | - Laurian Vlase
- Department of Pharmaceutical Technology and Biopharmaceutics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania;
| | - Ovidiu Oniga
- Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania; (A.C.C.); (I.I.); (C.M.); (O.O.)
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21
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Udah DC, Bakarey AS, Anetor GO, Omabe M, Edem VF, Ademowo OG, Anetor JI. Increased cancer risk in HIV-infected individuals occupationally exposed to chemicals: Depression of p53 as the key driver. PLOS GLOBAL PUBLIC HEALTH 2024; 4:e0002841. [PMID: 39042631 PMCID: PMC11265661 DOI: 10.1371/journal.pgph.0002841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 06/21/2024] [Indexed: 07/25/2024]
Abstract
The growing exposure to occupational chemicals and the spread of human immunodeficiency virus (HIV) infection are major global health issues. However, there is little data on the carcinogenic risk profile of HIV-infected individuals who have been occupationally exposed to chemical mixtures. This study therefore investigated the levels of cancer risk biomarkers in HIV-infected individuals exposed to occupational chemicals, exploring the relationship between apoptotic regulatory and oxidative response markers as a measure of cancer risk. Study participants (mean age 38.35±0.72 years) were divided into four groups according to their HIV status and occupational chemical exposure: 62 HIV-positive exposed (HPE), 66 HIV-positive unexposed (HPU), 60 HIV-negative exposed (HNE), and 60 HIV-negative unexposed (HNU). Serum p53, β-cell lymphoma-2 (bcl2), 8-hydroxydeoxyguanosine (8-OHdG), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured using standard methods. Clusters of differentiation 4 (CD4+) T-lymphocytes were enumerated using flow cytometry. Serum p53 and bcl2 levels in HPE (0.91±0.11ng/ml and 122.37±15.77ng/ml) were significantly lower than HNU (1.49±0.15ng/ml and 225.52±33.67ng/ml) (p < 0.05), respectively. Wildtype p53 and bcl2 were positively and significantly correlated with 8-OHdG (r = 0.35, p<0.001; r = 0.36, p<0.001) and SOD (r = 0.38, p<0.001; r = 0.39, p<0.001). After controlling for gender, age, BMI, and cigarette smoking, both HIV status and SOD activity were significantly associated with wildtype p53 and bcl2 (p < 0.05). Malondialdehyde was significantly higher in the HPE (0.72 ± 0.01 mg/ml) than in the HNE (0.68 ± 0.01 mg/ml) and HNU (0.67 ± 0.01 mg/ml) groups (p < 0.05). The HPE group showed significantly lower CD4 counts than the HNE and HNU groups. Individuals who are HIV-infected and occupationally exposed to chemicals have a constellation of depressed immunity, elevated oxidative stress, and loss of tumour suppressive functions, which together intensify cancer risk, providing valuable scientific and public health bases for preventive measures in this vulnerable population.
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Affiliation(s)
- Donald C. Udah
- Department of Chemical Pathology, Laboratory for Toxicology and Micronutrient Metabolism, College of Medicine, University of Ibadan, Ibadan, Nigeria
- JSI Research & Training Institute Inc. (JSI), Abuja, Nigeria
| | - Adeleye S. Bakarey
- Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
- Department of Biomedical Laboratory Science, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Gloria O. Anetor
- Department of Public Health Science, Faculty of Health Sciences, National Open University of Nigeria (NOUN), Abuja, Nigeria
| | - Maxwell Omabe
- Department of Medical Laboratory Sciences, School of Biomedical Science, Faculty of Health Science, Ebonyi State University, Nigeria
| | - Victory F. Edem
- Department of Immunology, University of Ibadan, Ibadan, Nigeria
| | - Olusegun G. Ademowo
- Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
- Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - John I. Anetor
- Department of Chemical Pathology, Laboratory for Toxicology and Micronutrient Metabolism, College of Medicine, University of Ibadan, Ibadan, Nigeria
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22
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Muro P, Zhang L, Li S, Zhao Z, Jin T, Mao F, Mao Z. The emerging role of oxidative stress in inflammatory bowel disease. Front Endocrinol (Lausanne) 2024; 15:1390351. [PMID: 39076514 PMCID: PMC11284038 DOI: 10.3389/fendo.2024.1390351] [Citation(s) in RCA: 33] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 06/19/2024] [Indexed: 07/31/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that affects the digestive system and includes Crohn's disease (CD) and ulcerative colitis (UC). Although the exact etiology of IBD remains uncertain, dysfunctional immunoregulation of the gut is believed to be the main culprit. Amongst the immunoregulatory factors, reactive oxygen species (ROS) and reactive nitrogen species (RNS), components of the oxidative stress event, are produced at abnormally high levels in IBD. Their destructive effects may contribute to the disease's initiation and propagation, as they damage the gut lining and activate inflammatory signaling pathways, further exacerbating the inflammation. Oxidative stress markers, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serum-free thiols (R-SH), can be measured in the blood and stool of patients with IBD. These markers are elevated in patients with IBD, and their levels correlate with the severity of the disease. Thus, oxidative stress markers can be used not only in IBD diagnosis but also in monitoring the response to treatment. It can also be targeted in IBD treatment through the use of antioxidants, including vitamin C, vitamin E, glutathione, and N-acetylcysteine. In this review, we summarize the role of oxidative stress in the pathophysiology of IBD, its diagnostic targets, and the potential application of antioxidant therapies to manage and treat IBD.
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Affiliation(s)
- Peter Muro
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Li Zhang
- Nanjing Lishui People’s Hospital, Zhongda Hospital, Southeast University, Nanjing, China
| | - Shuxuan Li
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Zihan Zhao
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Tao Jin
- Department of Gastrointestinal and Endoscopy, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China
| | - Fei Mao
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Zhenwei Mao
- The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
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23
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Bai J, Wu M, He Q, Wang H, Liao Y, Chen L, Chen S. Emerging Doped Metal-Organic Frameworks: Recent Progress in Synthesis, Applications, and First-Principles Calculations. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2306616. [PMID: 38342672 DOI: 10.1002/smll.202306616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 01/14/2024] [Indexed: 02/13/2024]
Abstract
Metal-organic frameworks (MOFs) are crystalline porous materials with a long-range ordered structure and excellent specific surface area and have found a wide range of applications in diverse fields, such as catalysis, energy storage, sensing, and biomedicine. However, their poor electrical conductivity and chemical stability, low capacity, and weak adhesion to substrates have greatly limited their performance. Doping has emerged as a unique strategy to mitigate the issues. In this review, the concept, classification, and characterization methods of doped MOFs are first introduced, and recent progress in the synthesis and applications of doped MOFs, as well as the rapid advancements and applications of first-principles calculations based on the density functional theory (DFT) in unraveling the mechanistic origin of the enhanced performance are summarized. Finally, a perspective is included to highlight the key challenges in doping MOF materials and an outlook is provided on future research directions.
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Affiliation(s)
- Jie Bai
- Department of Applied Chemistry, School of Chemical and Chemical Engineering, Chongqing University, Chongqing, 401331, P. R. China
| | - Mengcheng Wu
- Department of Applied Chemistry, School of Chemical and Chemical Engineering, Chongqing University, Chongqing, 401331, P. R. China
| | - Qingqing He
- Department of Applied Chemistry, School of Chemical and Chemical Engineering, Chongqing University, Chongqing, 401331, P. R. China
| | - Huayu Wang
- Department of Applied Chemistry, School of Chemical and Chemical Engineering, Chongqing University, Chongqing, 401331, P. R. China
| | - Yanxin Liao
- Department of Applied Chemistry, School of Chemical and Chemical Engineering, Chongqing University, Chongqing, 401331, P. R. China
| | - Lingyun Chen
- Department of Applied Chemistry, School of Chemical and Chemical Engineering, Chongqing University, Chongqing, 401331, P. R. China
| | - Shaowei Chen
- Department of Chemistry and Biochemistry, University of California, 1156 High Street, Santa Cruz, CA, 95060, United States
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24
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Salimi A, Haddadi S, Khezri S, Asgari B, Pourgholi M. Vanillic acid protects mortality and toxicity induced by N-ethyl-N-nitrosourea in mice; in vivo model of chronic lymphocytic leukemia. Toxicol Rep 2024; 12:389-396. [PMID: 38590344 PMCID: PMC10999465 DOI: 10.1016/j.toxrep.2024.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 03/13/2024] [Accepted: 03/27/2024] [Indexed: 04/10/2024] Open
Abstract
Alkylating agents such as N-Ethyl-N-Nitrosourea (ENU) are ubiquitous within living cells and in the environment. This study designed to evaluate the chemopreventive activity of vanillic acid on ENU-induced toxicity and carcinogenesis in mice as an animal model of chronic lymphocytic leukemia (CLL). The female, Swiss albino mice were divided into three groups each with 7 mice, group I received normal saline, group II, mice received ENU at a dose of 80 mg/kg body weight i.p. to induce CLL on the 31th day of the study, and group III, the mice pretreated with vanillic acid at a dose of 20 mg/kg body weight/day, i.p. up to 30 days and received ENU. The animals were monitored for weight changes and mortality during 120 days, and then were sacrificed for isolation of lymphocytes, as target cells in CLL. Cellular parameters like reactive oxygen species (ROS) formation, malondialdehyde (MDA) production, depletion of glutathione (GSH), mitochondrial membrane potential (MMP) and lysosomal membrane integrity were studied. We found that pretreatment with vanillic acid significantly increased the survival of mice up to 57%, delay in death time (30%) and prevented weight changes after exposure to ENU. In addition, it was found that vanillic acid protected ROS formation, lipid peroxidation mitochondrial dysfunction, and lysosomal membrane destabilization in isolated lymphocytes. These data suggest that vanillic acid exhibited significant protection against ENU-induced toxicity and carcinogenicity, which might be related to the protection of the mitochondria and lysosomes and the reduction of ROS formation and oxidative stress.
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Affiliation(s)
- Ahmad Salimi
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
- Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Iran
| | - Shadi Haddadi
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
- Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Saleh Khezri
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Bahare Asgari
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
- Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mahshad Pourgholi
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
- Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
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25
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Dong Y, Wang X, Wei L, Liu Z, Chu X, Xiong W, Liu W, Li X. The Effectiveness of Four Nicotinamide Adenine Dinucleotide (NAD +) Precursors in Alleviating the High-Glucose-Induced Damage to Hepatocytes in Megalobrama amblycephala: Evidence in NAD + Homeostasis, Sirt1/3 Activation, Redox Defense, Inflammatory Response, Apoptosis, and Glucose Metabolism. Antioxidants (Basel) 2024; 13:385. [PMID: 38671834 PMCID: PMC11047577 DOI: 10.3390/antiox13040385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 03/19/2024] [Accepted: 03/19/2024] [Indexed: 04/28/2024] Open
Abstract
The administration of NAD+ precursors is a potential approach to protect against liver damage and metabolic dysfunction. However, the effectiveness of different NAD+ precursors in alleviating metabolic disorders is still poorly elucidated. The current study was performed to compare the effectiveness of four different NAD+ precursors, including nicotinic acid (NA), niacinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN) in alleviating high-glucose-induced injury to hepatocytes in a fish model, Megalobrama amblycephala. An in vitro high-glucose model was successfully established to mimic hyperglycemia-induced damage to the liver, which was evidenced by the reduced cell viability, the increased transaminase activity, and the depletion of cellular NAD+ concentration. The NAD+ precursors all improved cell viability, with the maximal effect observed in NR, which also had the most potent NAD+ boosting capacity and a significant Sirt1/3 activation effect. Meanwhile, NR presented distinct and superior effects in terms of anti-oxidative stress, inflammation inhibition, and anti-apoptosis compared with NA, NAM, and NMN. Furthermore, NR could effectively benefit glucose metabolism by activating glucose transportation, glycolysis, glycogen synthesis and the pentose phosphate pathway, as well as inhibiting gluconeogenesis. Moreover, an oral gavage test confirmed that NR presented the most potent effect in increasing hepatic NAD+ content and the NAD+/NADH ratio among four NAD+ precursors. Together, the present study results demonstrated that NR is most effective in attenuating the high-glucose-induced injury to hepatocytes in fish compared to other NAD+ precursors.
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Affiliation(s)
| | | | | | | | | | | | | | - Xiangfei Li
- Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, China
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26
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Zhang L, Zhang J, Ye ZW, Muhammad A, Li L, Culpepper JW, Townsend DM, Tew KD. Adaptive changes in tumor cells in response to reductive stress. Biochem Pharmacol 2024; 219:115929. [PMID: 38000559 PMCID: PMC10895707 DOI: 10.1016/j.bcp.2023.115929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/14/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023]
Abstract
Reductive stress is characterized by an excess of cellular electron donors and can be linked with various human pathologies including cancer. We developed melanoma cell lines resistant to reductive stress agents: rotenone (ROTR), n-acetyl-L-cysteine, (NACR), or dithiothreitol (DTTR). Resistant cells divided more rapidly and had intracellular homeostatic redox-couple ratios that were shifted towards the reduced state. Resistance caused alterations in general cell morphology, but only ROTR cells had significant changes in mitochondrial morphology with higher numbers that were more isolated, fragmented and swollen, with greater membrane depolarization and decreased numbers of networks. These changes were accompanied by lower basal oxygen consumption and maximal respiration rates. Whole cell flux analyses and mitochondrial function assays showed that NACR and DTTR preferentially utilized tricarboxylic acid (TCA) cycle intermediates, while ROTR used ketone body substrates such as D, L-β-hydroxybutyric acid. NACR and DTTR cells had constitutively decreased levels of reactive oxygen species (ROS), although this was accompanied by activation of nuclear factor erythroid 2-related factor 2 (Nrf2), with concomitant increased expression of the downstream gene products such as glutathione S-transferase P (GSTP). Further adaptations included enhanced expression of endoplasmic reticulum proteins controlling the unfolded protein response (UPR). Although expression patterns of these UPR proteins were distinct between the resistant cells, a trend implied that resistance to reductive stress is accompanied by a constitutively increased UPR phenotype in each line. Overall, tumor cells, although tolerant of oxidative stress, can adapt their energy and survival mechanisms in lethal reductive stress conditions.
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Affiliation(s)
- Leilei Zhang
- Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA
| | - Jie Zhang
- Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA
| | - Zhi-Wei Ye
- Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA
| | - Aslam Muhammad
- Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA
| | - Li Li
- Department of Drug Discovery and Experimental Sciences, Medical University of South Carolina, 274 Calhoun Street MSC 141, Charleston, S.C. 29425-1410, USA
| | - John W Culpepper
- Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA
| | - Danyelle M Townsend
- Department of Drug Discovery and Experimental Sciences, Medical University of South Carolina, 274 Calhoun Street MSC 141, Charleston, S.C. 29425-1410, USA
| | - Kenneth D Tew
- Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 70 President St., DD410, Charleston, SC 29425, USA.
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27
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Kong DH, Ji YX, Zhang BY, Li KC, Liao ZY, Wang H, Zhou JX, Wang QJ. Effects of hydroxy methionine zinc on growth performance, immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii). FISH & SHELLFISH IMMUNOLOGY 2024; 144:109231. [PMID: 37984613 DOI: 10.1016/j.fsi.2023.109231] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 11/07/2023] [Accepted: 11/12/2023] [Indexed: 11/22/2023]
Abstract
This study aimed to evaluate the effects of varying zinc (Zn) levels on the growth performance, non-specific immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii (P. clarkii)). Adopting hydroxy methionine zinc (Zn-MHA) as the Zn source, 180 healthy crayfish with an initial body mass of 6.50 ± 0.05 g were randomly divided into the following five groups: X1 (control group) and groups X2, X3, X4, and X5, which were fed the basal feed supplemented with Zn-MHA with 0, 15, 30, 60, and 90 mg kg-1, respectively. The results indicated that following the addition of various concentrations of Zn-MHA to the diet, the following was observed: Specific growth rate (SGR), weight gain rate (WGR), total protein (TP), total cholesterol (TC), the activities of alkaline phosphatase (AKP), phenoloxidase (PO), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT), the expression of CTL, GPX, and CuZn-SOD genes demonstrated a trend of rising and then declining-with a maximum value in group X4-which was significantly higher than that in group X1 (P < 0.05). Zn deposition in the intestine and hepatopancreas, the activity of GSH-PX, and the expression of GSH-PX were increased, exhibiting the highest value in group X5. The malonaldehyde (MDA) content was significantly reduced, with the lowest value in group X4, and the MDA content of the Zn-MHA addition groups were significantly lower than the control group (P < 0.05). In the analysis of the intestinal microbiota of P. clarkii, the number of operational taxonomic units in group X4 was the highest, and the richness and diversity indexes of groups X3 and X4 were significantly higher than those in group X1 (P < 0.05). Meanwhile, the dietary addition of Zn-MHA decreased and increased the relative abundance of Proteobacteria and Tenericutes, respectively. These findings indicate that supplementation of dietary Zn-MHA at an optimum dose of 60 mg kg-1 may effectively improve growth performance, immune response, antioxidant capacity, and intestinal microbiota richness and species diversity in crayfish.
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Affiliation(s)
- De-Hua Kong
- College of Animal Science and Technology, Jilin Agricultural University, Jilin Changchun, 130118, China
| | - Yu-Xiang Ji
- College of Animal Science and Technology, Jilin Agricultural University, Jilin Changchun, 130118, China
| | - Bao-Yuan Zhang
- College of Animal Science and Technology, Jilin Agricultural University, Jilin Changchun, 130118, China
| | - Kuo-Chen Li
- College of Animal Science and Technology, Jilin Agricultural University, Jilin Changchun, 130118, China
| | - Zi-Yan Liao
- College of Animal Science and Technology, Jilin Agricultural University, Jilin Changchun, 130118, China
| | - Hao Wang
- College of Animal Medicine, Jilin Agricultural University, Jilin Changchun, 130118, China
| | - Jing-Xiang Zhou
- College of Animal Science and Technology, Jilin Agricultural University, Jilin Changchun, 130118, China; College of Animal Medicine, Jilin Agricultural University, Jilin Changchun, 130118, China.
| | - Qiu-Ju Wang
- College of Life Sciences, Jilin Agricultural University, Jilin Changchun, 130118, China; College of Animal Medicine, Jilin Agricultural University, Jilin Changchun, 130118, China.
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Terpiłowska S, Pięta E, Roman M, Paluszkiewicz C, Kwiatek WM. Spectroscopic imaging to assess biochemical alterations in liver carcinoma cells exposed to transition metals. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2023; 303:123228. [PMID: 37579664 DOI: 10.1016/j.saa.2023.123228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 07/17/2023] [Accepted: 08/01/2023] [Indexed: 08/16/2023]
Abstract
Despite the invaluable role of transition metals in every living organism, it should be remembered that failure to maintain the proper balance and exceed the appropriate dose may have the opposite effect. In the era of such a popular and propagated need for supplementation in the media, one should bear in mind the harmful effects that may become the result of improper and excessive intake of transition metals. This article establishes the feasibility of Raman (RS) and Fourier-transform infrared (FT-IR) spectroscopic imaging at the single-cell level to investigate the cellular response to various transition metals. These two non-destructive and perfectly complementary methods allow for in-depth monitoring of changes taking place within the cell under the influence of the agent used. HepG2 liver carcinoma cells were exposed to chromium, iron, cobalt, molybdenum, and nickel at 1 and 2 mM concentrations. Spectroscopic results were further supported by biological evaluation of selected caspases concentration. The caspase- 3, 6, 8, 9, and 12 concentrations were determined with the use of the enzyme-linked immunosorbent assay (ELISA) method. This study shows the induction of apoptosis in the intrinsic pathway by all studied transition metals. Cellular metabolism alterations are induced by mitochondrial metabolism changes and endoplasmic reticulum (ER) metabolism variations. Moreover, nickel induces not only the intrinsic pathway of apoptosis but also the extrinsic pathway of this process.
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Affiliation(s)
- Sylwia Terpiłowska
- Jan Kochanowski University of Kielce, Collegium Medicum, Department of Surgical Medicine with the Laboratory of Medical Genetics, IX Wieków Kielc 19A Av., 25-317 Kielce, Poland.
| | - Ewa Pięta
- Institute of Nuclear Physics Polish Academy of Sciences, PL-31342 Krakow, Poland
| | - Maciej Roman
- Institute of Nuclear Physics Polish Academy of Sciences, PL-31342 Krakow, Poland
| | | | - Wojciech M Kwiatek
- Institute of Nuclear Physics Polish Academy of Sciences, PL-31342 Krakow, Poland
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You T, Li Y, Li B, Wu S, Jiang X, Fu D, Xin J, Huang Y, Jin L, Hu C. Caveolin-1 protects against liver damage exacerbated by acetaminophen in non-alcoholic fatty liver disease by inhibiting the ERK/HIF-1α pathway. Mol Immunol 2023; 163:104-115. [PMID: 37769575 DOI: 10.1016/j.molimm.2023.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 08/15/2023] [Accepted: 09/05/2023] [Indexed: 10/03/2023]
Abstract
Acetaminophen (APAP) is a common antipyretic and analgesic drug that can cause long-term liver damage after an overdose. Non-alcoholic fatty liver disease (NAFLD) increases susceptibility to APAP. In NAFLD, excessive accumulation of lipids leads to an abnormal increase in hypoxia-inducible factor-1α (HIF-1α). Caveolin-1 (CAV1) may protect against NAFLD by inhibiting HIF-1α. This research aimed to determine whether CAV1 could attenuate APAP-exacerbated liver injury in NAFLD by inhibiting oxidative stress involving HIF-1α. In this study, 7-week-old C57BL/6 mice were fed a high-fat diet (HFD) for eight weeks, followed by the instillation of APAP. Levels of oxidative stress and liver lipid deposition were determined, and p-ERK1/2 and HIF-1α protein expression were measured by the Western blot (WB) method. In the APAP-treated group, the level of CAV1 was decreased, while the levels of HIF-1α and reactive oxygen species (ROS) were significantly increased. AML12 cells were treated with a mixture of palmitic acid (PA) and oleic acid (OA) (1:2 mix) for 48 h, and APAP was added for the last 24 h. Overexpression of CAV1 in AML12 cells significantly inhibited the expression of ROS and HIF-1α. And the results of immunofluorescence after treatment with CAV1-SiRNA showed that the HIF-1α levels were significantly increased in mitochondria. In conclusion, our experimental results suggest that CAV1 has a protective function in the fatty liver based on preventing oxidative stress, which involves HIF-1α. Thus, upregulation of CAV1 may attenuate APAP-exacerbated liver injury in NAFLD.
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Affiliation(s)
- Tingyu You
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China
| | - Yu Li
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China
| | - Bowen Li
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China
| | - Shuai Wu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China
| | - Xiangfu Jiang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China
| | - Dongdong Fu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China
| | - Jiao Xin
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China
| | - Yan Huang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China
| | - Lei Jin
- Department of Infectious diseases, The Second Affiliated Hospital of Anhui Medical University, China.
| | - Chengmu Hu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for Liver Diseases of Anhui Medical University, School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China.
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30
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Zhou Y, Xu R, Gao Z, Miao J, Pan L. Insights into mechanism of DNA damage and repair-apoptosis in digestive gland of female scallop Chlamys farreri under benzo[a]pyrene exposure during reproductive stage. Comp Biochem Physiol C Toxicol Pharmacol 2023; 273:109738. [PMID: 37661044 DOI: 10.1016/j.cbpc.2023.109738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/25/2023] [Accepted: 08/30/2023] [Indexed: 09/05/2023]
Abstract
As one of the most carcinogenic persistent organic pollutants (POPs), benzo[a]pyrene (B [a]P) brings high toxicity to marine bivalves. Digestive gland is the most important metabolism-related organ of aquatic animals. This study conducted the digestive gland transcriptome of Chlamys farreri under B[a]P treatment at reproductive stages. And the reproductive-stage dependence metabolism-DNA repair-apoptosis process of scallops under 0, 0.04, 0.4 and 4 μg/L B[a]P was studied by qRT-PCR. The results demonstrated that the detoxification metabolism was disturbed after ovulation except for CYP3A4. In antioxidant system, antioxidant enzyme CAT and GPX, and GGT1 (one of the non-enzymatic antioxidants synthesis gene) continuously served the function of antioxidant defense. Three types of DNA repair were activated under B[a]P stress, however, DNA strand breaks were still serious. B[a]P exposure weakened death receptor pathway as well as enhanced mitochondrial pathway, surprisingly suppressing apoptosis in scallops. In addition, ten indicators were screened by Spearman correlation analysis. This study will provide sound theoretical basis for bivalve toxicology and contribute to the biomonitoring of marine POPs pollution.
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Affiliation(s)
- Yueyao Zhou
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, PR China
| | - Ruiyi Xu
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, PR China
| | - Zhongyuan Gao
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, PR China
| | - Jingjing Miao
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, PR China
| | - Luqing Pan
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, PR China.
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Wang X, Chen F, Lu J, Wu M, Cheng J, Xu W, Li Z, Zhang Y. Developmental and cardiovascular toxicities of acetochlor and its chiral isomers in zebrafish embryos through oxidative stress. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 896:165296. [PMID: 37406693 DOI: 10.1016/j.scitotenv.2023.165296] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 06/28/2023] [Accepted: 07/01/2023] [Indexed: 07/07/2023]
Abstract
Acetochlor (ACT) is a widely used pesticide, yet the environmental and health safety of its chiral isomers remains inadequately evaluated. In this study, we evaluated the toxicity of ACT and its chiral isomers in a zebrafish model. Our findings demonstrate that ACT and its chiral isomers disrupt early zebrafish embryo development, inducing oxidative stress, abnormal lipid metabolism, and apoptosis. Additionally, ACT and its chiral isomers lead to cardiovascular damage, including reduced heart rate, decreased red blood cell (RBC) flow rate, and vascular damage. We further observed that (+)-S-ACT has a significant impact on the transcription of genes involved in cardiac and vascular development, including tbx5, hand2, nkx2.5, gata4, vegfa, dll4, cdh5, and vegfc. Our study highlights the potential risk posed by different conformations of chiral isomeric pesticides and raises concerns regarding their impact on human health. Overall, our results suggest that the chiral isomers of ACT induce developmental defects and cardiovascular toxicity in zebrafish, with (+)-S-ACT being considerably more toxic to zebrafish than (-)-R-ACT.
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Affiliation(s)
- Xin Wang
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Fan Chen
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Jian Lu
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Mengqi Wu
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Jiagao Cheng
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Wenping Xu
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Zhong Li
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
| | - Yang Zhang
- Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
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32
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Souza MCO, González N, Rovira J, Herrero M, Marquès M, Nadal M, Barbosa F, Domingo JL. Assessment of urinary aromatic amines in Brazilian pregnant women and association with DNA damage: Influence of genetic diversity, lifestyle, and environmental and socioeconomic factors. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 335:122366. [PMID: 37572848 DOI: 10.1016/j.envpol.2023.122366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 08/09/2023] [Accepted: 08/10/2023] [Indexed: 08/14/2023]
Abstract
Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p-aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential.
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Affiliation(s)
- Marília Cristina Oliveira Souza
- University of Sao Paulo, School of Pharmaceutical Sciences of Ribeirao Preto, Department of Clinical Analyses, Toxicology, and Food Sciences (Analytical and System Toxicology Laboratory), Avenida do Café s/n◦, 14040-903, Ribeirao Preto, Sao Paulo, Brazil; Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Sant Llorenç 21, 43201, Reus, Catalonia, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Catalonia, Spain.
| | - Neus González
- University of Sao Paulo, School of Pharmaceutical Sciences of Ribeirao Preto, Department of Clinical Analyses, Toxicology, and Food Sciences (Analytical and System Toxicology Laboratory), Avenida do Café s/n◦, 14040-903, Ribeirao Preto, Sao Paulo, Brazil; Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Sant Llorenç 21, 43201, Reus, Catalonia, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Catalonia, Spain
| | - Joaquim Rovira
- Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Sant Llorenç 21, 43201, Reus, Catalonia, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Catalonia, Spain; Environmental Engineering Laboratory, Department of Chemical Engineering, University Rovira and Virgili, Paisos Catalans Avenue 26, 43007, Tarragona, Catalonia, Spain
| | - Marta Herrero
- Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Sant Llorenç 21, 43201, Reus, Catalonia, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Catalonia, Spain
| | - Montse Marquès
- Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Sant Llorenç 21, 43201, Reus, Catalonia, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Catalonia, Spain
| | - Martí Nadal
- Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Sant Llorenç 21, 43201, Reus, Catalonia, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Catalonia, Spain
| | - Fernando Barbosa
- University of Sao Paulo, School of Pharmaceutical Sciences of Ribeirao Preto, Department of Clinical Analyses, Toxicology, and Food Sciences (Analytical and System Toxicology Laboratory), Avenida do Café s/n◦, 14040-903, Ribeirao Preto, Sao Paulo, Brazil
| | - José Luis Domingo
- Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Sant Llorenç 21, 43201, Reus, Catalonia, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Catalonia, Spain
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Rana I, Nguyen PK, Rigutto G, Louie A, Lee J, Smith MT, Zhang L. Mapping the key characteristics of carcinogens for glyphosate and its formulations: A systematic review. CHEMOSPHERE 2023; 339:139572. [PMID: 37474029 DOI: 10.1016/j.chemosphere.2023.139572] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 07/16/2023] [Accepted: 07/17/2023] [Indexed: 07/22/2023]
Abstract
Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic evidence in 2015. Since then, numerous studies of glyphosate and its formulations (GBF) have emerged. These studies can be evaluated for cancer hazard identification with the newly described ten key characteristics (KC) of carcinogens approach. Our objective was to assess all in vivo, ex vivo, and in vitro mechanistic studies of human and experimental animals (mammals) that compared exposure to glyphosate/GBF with low/no exposure counterparts for evidence of the ten KCs. A protocol with our methods adhering to PRISMA guidelines was registered a priori (INPLASY202180045). Two blinded reviewers screened all in vivo, ex vivo, and in vitro studies of glyphosate/GBF exposure in humans/mammals reporting any KC-related outcome available in PubMed before August 2021. Studies that met inclusion criteria underwent data extraction conducted in duplicate for each KC outcome reported along with key aspects of internal/external validity, results, and reference information. These data were used to construct a matrix that was subsequently analyzed in the program R to conduct strength of evidence and quality assessments. Of the 2537 articles screened, 175 articles met inclusion criteria, from which we extracted >50,000 data points related to KC outcomes. Data analysis revealed strong evidence for KC2, KC4, KC5, KC6, KC8, limited evidence for KC1 and KC3, and inadequate evidence for KC7, KC9, and KC10. Notably, our in-depth quality analyses of genotoxicity (KC2) and endocrine disruption (KC8) revealed strong and consistent positive findings. For KC2, we found: 1) studies conducted in humans and human cells provided stronger positive evidence than counterpart animal models; 2) GBF elicited a stronger effect in both human and animal systems when compared to glyphosate alone; and 3) the highest quality studies in humans and human cells consistently revealed strong evidence of genotoxicity. Our analysis of KC8 indicated that glyphosate's ability to modulate hormone levels and estrogen receptor activity is sensitive to both exposure concentration and formulation. The modulations observed provide clear evidence that glyphosate interacts with receptors, alters receptor activation, and modulates the levels and effects of endogenous ligands (including hormones). Our findings strengthen the mechanistic evidence that glyphosate is a probable human carcinogen and provide biological plausibility for previously reported cancer associations in humans, such as non-Hodgkin lymphoma. We identified potential molecular interactions and subsequent key events that were used to generate a probable pathway to lymphomagenesis.
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Affiliation(s)
- Iemaan Rana
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, United States
| | - Patton K Nguyen
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, United States
| | - Gabrielle Rigutto
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, United States
| | - Allen Louie
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, United States
| | - Jane Lee
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, United States
| | - Martyn T Smith
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, United States
| | - Luoping Zhang
- Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, United States.
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Bakam BY, Pambe JCN, Grey T, Maxeiner S, Rutz J, Njamen D, Blaheta RA, Zingue S. Cucumis sativus (Cucurbitaceae) seed oil prevents benzo(a)pyrene-induced prostate cancer in vitro and in vivo. ENVIRONMENTAL TOXICOLOGY 2023; 38:2069-2083. [PMID: 37310102 DOI: 10.1002/tox.23830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 04/26/2023] [Accepted: 05/01/2023] [Indexed: 06/14/2023]
Abstract
Despite enormous progress in modern medicine, prostate cancer (PCa) remains a major public health problem due to its high incidence and mortality. Although studies have shown in vitro antitumor effects of cucurbitacins from Cucumis sativus, the in vivo anticancer effect of the seed oil as a whole, has yet to be demonstrated. The present study evaluated the in vitro anticancer mechanisms of C. sativus (CS) seed oil and its possible chemopreventive potential on benzo(a)pyrene (BaP)-induced PCa in Wistar rat. In vitro cell growth, clone formation, cell death mechanism, cell adhesion and migration as well as expression of integrins β-1 and β-4 were assessed. In vivo PCa was induced in 56 male rats versus 8 normal control rats, randomized in normal (NOR) and negative (BaP) control groups which, received distilled water; the positive control group (Caso) was treated with casodex (13.5 mg/kg BW). One group received the total seed extract at the dose of 500 mg/kg BW; while the remaining three groups were treated with CS seed oil at 42.5, 85, and 170 mg/kg BW. The endpoints were: morphologically (prostate tumor weight and volume), biochemically (total protein, prostate specific antigen (PSA), oxidative stress markers such as MDA, GSH, catalase, and SOD) and histologically. As results, CS seed oil significantly and concentration-dependently reduced the DU145 prostate cancer cell growth and clone formation (optimum = 100 μg/mL). It slightly increased the number of apoptotic cells and inhibited the migration and invasion of DU145 cells, while it decreased their adhesion to immobilized collagen and fibrinogen. The expression of integrin β-1 and β-4 was increased in presence of 100 μg/mL CS oil. In vivo, the BaP significantly elevated the incidence of PC tumors (75%), the total protein and PSA levels, pro-inflammatory cytokines (TNF-α, IL-1, and IL-6) and MDA levels compared to NOR. CS seeds oil significantly counteracted the effect of BaP by decreasing significantly the PC incidence (12.5%), and increasing the level of antioxidant (SOD, GSH, and catalase) and anti-inflammatory cytokine IL-10 in serum. While in BaP group PCa adenocarninoma was the most representative neoplasm, rats treated with 85 and 170 mg/kg prevented it in the light of the casodex. It is conclude that CS may provide tumor suppressive effects in vitro and in vivo which makes it an interesting candidate to support the current treatment protocol.
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Affiliation(s)
- Berlise Yengwa Bakam
- Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon
| | - Judith Christiane Ngo Pambe
- Department of Morphological Sciences and Pathological Anatomy, Faculty of Medicine and Biomedical Sciences, University of Garoua, Garoua, Cameroon
| | - Timothy Grey
- Department of Urology and Pediatric Urology, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, Mainz, Germany
| | - Sebastian Maxeiner
- Department of Urology and Pediatric Urology, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, Mainz, Germany
| | - Jochen Rutz
- Department of Urology and Pediatric Urology, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, Mainz, Germany
| | - Dieudonne Njamen
- Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon
| | - Roman A Blaheta
- Department of Urology and Pediatric Urology, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, Mainz, Germany
| | - Stéphane Zingue
- Department of Urology, University Hospital Frankfurt, Johann Wolfgang Goethe Universität, Frankfurt am Main, Germany
- Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, Yaounde, Cameroon
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Ishteyaque S, Yadav KS, Verma S, Washimkar KR, Mugale MN. CYP2E1 triggered GRP78/ATF6/CHOP signaling axis inhibit apoptosis and promotes progression of hepatocellular carcinoma. Arch Biochem Biophys 2023; 745:109701. [PMID: 37499993 DOI: 10.1016/j.abb.2023.109701] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 07/09/2023] [Accepted: 07/24/2023] [Indexed: 07/29/2023]
Abstract
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Cytochrome P450 2E1 (CYP2E1) is an enzyme, primarily involved in the metabolism of xenobiotics and procarcinogens. The present study was designed to investigate the potential role of CYP2E1 triggered endoplasmic reticulum stress in the progression of HCC through inhibition of apoptosis. In vitro CYP2E1 promotes HepG2 cell migration, reduced chromatin condensation, enhanced intracellular ROS accumulation and induce cell cycle progression. Conversely this effect was averted by CYP2E1 siRNA, selective inhibitor Diallyl sulphide (DAS) and antioxidants (vitamin C and E). In vivo Diethylnitrosamine (DEN) induced HCC rats showed decreased body weight and increased relative liver weight. Moreover, macro trabecular-massive HCC (MTM-HCC) histological subtyping showed pathological features like well-differentiated tumors, micro-trabecular and pseudo glandular patterns, megakaryocytes and cholestasis. Masson's trichrome staining revealed an intensive accumulation of collagen fibers in the extracellular matrix (ECM). Increased CYP2E1, VEGF and PCNA enhance the carcinogenicity as revealed in immunohistochemistry results. Immunoblot analysis showed reduced expression of copper-zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) in cytosolic as well as mitochondrial fraction of rat liver tissue respectively. Also, increased level of CYP2E1 stimulated the upregulation of unfolded proteins response (UPR) and ER stress-related proteins such as Glucose regulatory protein 78 (GRP78), activating transcription factor 6 (ATF6) and CCAAT enhancer-binding protein (C/EBP) homologous protein (CHOP). Meanwhile, CYP2E1 stimulated ER-stress reduces BCL2 and downregulates the cleaved caspase 3 thus suppresses apoptosis. in. Furthermore, immunofluorescence revealed increased expression level of α-SMA in the HCC rat liver tissue. The level of CYP2E1 mRNA was significantly increased. Altogether, these findings indicate that CYP2E1 has a dynamic role in the pathogenesis of HCC and might be a budding agent in liver carcinogenesis therapy.
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Affiliation(s)
- Sharmeen Ishteyaque
- Division of Cancer Biology CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Karan Singh Yadav
- Division of Cancer Biology CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Smriti Verma
- Division of Cancer Biology CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Kaveri R Washimkar
- Division of Cancer Biology CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Madhav Nilakanth Mugale
- Division of Cancer Biology CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
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Liu X, Bao X, Yang J, Zhu X, Li Z. Preliminary study on toxicological mechanism of golden cuttlefish (Sepia esculenta) larvae exposed to cd. BMC Genomics 2023; 24:503. [PMID: 37649007 PMCID: PMC10466719 DOI: 10.1186/s12864-023-09630-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Accepted: 08/27/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND Cadmium (Cd) flows into the ocean with industrial and agricultural pollution and significantly affects the growth and development of economic cephalopods such as Sepia esculenta, Amphioctopus fangsiao, and Loligo japonica. As of now, the reasons why Cd affects the growth and development of S. esculenta are not yet clear. RESULTS In this study, transcriptome and four oxidation and toxicity indicators are used to analyze the toxicological mechanism of Cd-exposed S. esculenta larvae. Indicator results indicate that Cd induces oxidative stress and metal toxicity. Functional enrichment analysis results suggest that larval ion transport, cell adhesion, and some digestion and absorption processes are inhibited, and the cell function is damaged. Comprehensive analysis of protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore S. esculenta larval toxicological mechanisms, and we find that among the 20 identified key genes, 14 genes are associated with neurotoxicity. Most of them are down-regulated and enriched to the neuroactive ligand-receptor interaction signaling pathway, suggesting that larval nervous system might be destroyed, and the growth, development, and movement process are significantly affected after Cd exposure. CONCLUSIONS S. esculenta larvae suffered severe oxidative damage after Cd exposure, which may inhibit digestion and absorption functions, and disrupt the stability of the nervous system. Our results lay a function for understanding larval toxicological mechanisms exposed to heavy metals, promoting the development of invertebrate environmental toxicology, and providing theoretical support for S. esculenta artificial culture.
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Affiliation(s)
- Xiumei Liu
- College of Life Sciences, Yantai University, Yantai, 264005, China
| | - Xiaokai Bao
- School of Agriculture, Ludong University, Yantai, 264025, China
| | - Jianmin Yang
- School of Agriculture, Ludong University, Yantai, 264025, China
| | - Xibo Zhu
- Fishery Technology Service Center of Lanshan District, Rizhao, 276800, China.
| | - Zan Li
- School of Agriculture, Ludong University, Yantai, 264025, China.
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Fang C, Fang L, Di S, Yu Y, Wang X, Wang C, Jin Y. Characterization of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD)-induced cardiotoxicity in larval zebrafish (Danio rerio). THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 882:163595. [PMID: 37094682 DOI: 10.1016/j.scitotenv.2023.163595] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 04/14/2023] [Accepted: 04/15/2023] [Indexed: 05/03/2023]
Abstract
N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is a type of p-phenylenediamine (PPD), which is widely used in the manufacture of rubber tires owing to its excellent antiozonant properties. In this study, the developmental cardiotoxicity of 6PPD was evaluated in zebrafish larvae, and the LC50 was approximately 737 μg/L for the larvae at 96 h post fertilization (hpf). In the 6PPD treatment of 100 μg/L, the accumulation concentrations of 6PPD were up to 2658 ng/g in zebrafish larvae, and 6PPD induced significant oxidative stress and cell apoptosis in the early developmental stages of zebrafish. Transcriptome analysis showed that 6PPD exposure could potentially cause cardiotoxicity in larval zebrafish by affecting the transcription of the genes related to the calcium signal pathway and cardiac muscle contraction. The genes related to calcium signaling pathway (slc8a2b, cacna1ab, cacna1da, and pln) were verified by qRT-PCR, which were significantly downregulated in larval zebrafish after exposing to 100 μg/L of 6PPD. Simultaneously, the mRNA levels of the genes related to cardiac functions (myl7, sox9, bmp10, and myh71) also respond accordingly. H&E staining and heart morphology investigation indicated that cardiac malformation occurred in zebrafish larvae exposed to 100 μg/L of 6PPD. Furthermore, the phenotypic observation of transgenic Tg (myl7: EGFP) zebrafish also confirmed that 100 μg/L of 6PPD exposure could change the distance of atria and ventricles of the heart and inhibit some key genes (cacnb3a, ATP2a1l, ryr1b) related to cardiac function in larval zebrafish. These results revealed the toxic effects of 6PPD on the cardiac system of zebrafish larvae.
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Affiliation(s)
- Chanlin Fang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Liya Fang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Shanshan Di
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China
| | - Yundong Yu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China; State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China
| | - Xinquan Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China.
| | - Caihong Wang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Yuanxiang Jin
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
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Veltman CHJ, Pennings JLA, van de Water B, Luijten M. An Adverse Outcome Pathway Network for Chemically Induced Oxidative Stress Leading to (Non)genotoxic Carcinogenesis. Chem Res Toxicol 2023. [PMID: 37156502 DOI: 10.1021/acs.chemrestox.2c00396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
Nongenotoxic (NGTX) carcinogens induce cancer via other mechanisms than direct DNA damage. A recognized mode of action for NGTX carcinogens is induction of oxidative stress, a state in which the amount of oxidants in a cell exceeds its antioxidant capacity, leading to regenerative proliferation. Currently, carcinogenicity assessment of environmental chemicals primarily relies on genetic toxicity end points. Since NGTX carcinogens lack genotoxic potential, these chemicals may remain undetected in such evaluations. To enhance the predictivity of test strategies for carcinogenicity assessment, a shift toward mechanism-based approaches is required. Here, we present an adverse outcome pathway (AOP) network for chemically induced oxidative stress leading to (NGTX) carcinogenesis. To develop this AOP network, we first investigated the role of oxidative stress in the various cancer hallmarks. Next, possible mechanisms for chemical induction of oxidative stress and the biological effects of oxidative damage to macromolecules were considered. This resulted in an AOP network, of which associated uncertainties were explored. Ultimately, development of AOP networks relevant for carcinogenesis in humans will aid the transition to a mechanism-based, human relevant carcinogenicity assessment that involves a substantially lower number of laboratory animals.
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Affiliation(s)
- Christina H J Veltman
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands
- Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, 2333 CC Leiden, The Netherlands
| | - Jeroen L A Pennings
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands
| | - Bob van de Water
- Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, 2333 CC Leiden, The Netherlands
| | - Mirjam Luijten
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands
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Hu Y, Yan Z, He Y, Li Y, Li M, Li Y, Zhang D, Zhao Y, Ommati MM, Wang J, Huo M, Wang J. Ameliorative effects of different doses of selenium against fluoride-triggered apoptosis and oxidative stress-mediated renal injury in rats through the activation of Nrf2/HO-1/NQO1 signaling pathway. Food Chem Toxicol 2023; 174:113647. [PMID: 36736877 DOI: 10.1016/j.fct.2023.113647] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 01/25/2023] [Accepted: 01/31/2023] [Indexed: 02/04/2023]
Abstract
Excess fluoride (F) exposure can cause oxidative stress in the kidney. As an antioxidant, selenium (Se) can potentially protect the kidney from F-induced injury in rats. Hence, the histopathological, renal biochemical, oxidative stress, and apoptotic-related indices upon exposure to 100 mg/L sodium fluoride (NaF) and various doses of sodium selenite (Na2SeO3; 0.5, 1, and 2 mg/L) were assessed. Our results demonstrated that F-mediated renal structural damage and apoptosis elevated the content of serum creatinine (SCr), inhibited the activity of catalase (CAT) in serum, and increased the production of reactive oxygen species (ROS) in kidney and malondialdehyde (MDA) in serum. Interestingly, 1 mg/L dietary supplementation of Se tangibly mitigated these injuries. Furthermore, F could also change the gene and protein expression of the nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase1 (NQO1). Concomitantly, the different concentrations of Se notably alleviated their expression. Taken together, 1-2 mg/L Se ameliorated F-induced renal injury through oxidative stress and apoptosis-related routes. The recorded ameliorative effects might be related to the activation of the Nrf2/HO-1/NQO1 signaling pathway.
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Affiliation(s)
- Yingjun Hu
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - Zipeng Yan
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - Yang He
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - Yan Li
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - Meng Li
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - Yuanyuan Li
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - DingLi Zhang
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - Yangfei Zhao
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - Mohammad Mehdi Ommati
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - Jundong Wang
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China
| | - Meijun Huo
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China.
| | - Jinming Wang
- College of Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, PR China.
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40
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Fahim TM, Mohamed MAELH, Abdelrahman SSM, Lotfy DM. Beneficial Effect of Rosuvastatin Therapy on Spleen Injury Induced by Gamma Irradiation in Rats: Targeting Nrf2/EPRE Pathway. Dose Response 2023; 21:15593258231179900. [PMID: 37255693 PMCID: PMC10226320 DOI: 10.1177/15593258231179900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2023] Open
Abstract
Purpose The present study investigates the new approach of rosuvastatin (RUV) administration as a drug for the management of spleen injury induced by gamma irradiation. Main Methods Forty rats were used and divided equally into 4 groups: control group, irradiated group, IRR + rosuvastatin group (10 mg/Kg b. wt), and IRR + rosuvastatin group (20 mg/kg b. wt) for 7 days orally. Results The possible curative effect can be illustrated via the improvement of hematopoietic cell count (Hb, RBCs, and WBCs) and oxidative stress markers (MDA and GST) in addition to biochemical parameters including [heme oxigenase-1 (HO-1), nuclear erythroid 2-related factor (Nrf2), NOD-, LRR- and pyrin domain- containing protein 3 (NLRP3) inflammasome] and immune assay of nuclear factor kappa beta (NF-kB P65) and inducible nitric oxide synthase (iNOS). Histological pictures emphasize the biochemical findings. Rosuvastatin treatments by using two different doses improve the tested parameters. High-dose administration of RUV (20 mg/kg p.o.) recorded better results than the low dose (10 mg/kg p.o.). Conclusion Our results suggested that rosuvastatin reversed the radiation-induced spleen-damaging effects. So, RUV can be introduced to the market as a new therapy for the management of spleen damages.
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Affiliation(s)
- Thanaa M. Fahim
- Drug Radiation Research Department, National Center for Radiation Research and
Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt
| | - Marwa Abd EL-Hameed Mohamed
- Drug Radiation Research Department, National Center for Radiation Research and
Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt
| | | | - Dina M. Lotfy
- Drug Radiation Research Department, National Center for Radiation Research and
Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt
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Li D, Shen L, Zhang D, Wang X, Wang Q, Qin W, Gao Y, Li X. Ammonia-induced oxidative stress triggered proinflammatory response and apoptosis in pig lungs. J Environ Sci (China) 2023; 126:683-696. [PMID: 36503793 DOI: 10.1016/j.jes.2022.05.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 05/06/2022] [Accepted: 05/07/2022] [Indexed: 06/17/2023]
Abstract
Ammonia, a common toxic gas, is not only one of the main causes of haze, but also can enter respiratory tract and directly affect the health of humans and animals. Pig was used as an animal model for exploring the molecular mechanism and dose effect of ammonia toxicity to lung. In this study, the apoptosis of type II alveolar epithelial cells was observed in high ammonia exposure group using transmission electron microscopy. Gene and protein expression analysis using transcriptome sequencing and western blot showed that low ammonia exposure induced T-cell-involved proinflammatory response, but high ammonia exposure repressed the expression of DNA repair-related genes and affected ion transport. Moreover, high ammonia exposure significantly increased 8-hydroxy-2-deoxyguanosine (8-OHdG) level, meaning DNA oxidative damage occurred. In addition, both low and high ammonia exposure caused oxidative stress in pig lungs. Integrated analysis of transcriptome and metabolome revealed that the up-regulation of LDHB and ND2 took part in high ammonia exposure-affected pyruvate metabolism and oxidative phosphorylation progress, respectively. Inclusion, oxidative stress mediated ammonia-induced proinflammatory response and apoptosis of porcine lungs. These findings may provide new insights for understanding the ammonia toxicity to workers in livestock farms and chemical fertilizer plants.
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Affiliation(s)
- Daojie Li
- Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China
| | - Long Shen
- Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China
| | - Di Zhang
- Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China
| | - Xiaotong Wang
- Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China
| | - Qiankun Wang
- Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China
| | - Wenhao Qin
- College of Science, Huazhong Agricultural University, Wuhan 430070, China
| | - Yun Gao
- College of Engineering, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China
| | - Xiaoping Li
- Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China.
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Feng T, Tao Y, Yan Y, Lu S, Li Y, Zhang X, Qiang J. Transcriptional Inhibition of AGPAT2 Induces Abnormal Lipid Metabolism and Oxidative Stress in the Liver of Nile Tilapia Oreochromis niloticus. Antioxidants (Basel) 2023; 12:antiox12030700. [PMID: 36978948 PMCID: PMC10045202 DOI: 10.3390/antiox12030700] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 03/01/2023] [Accepted: 03/01/2023] [Indexed: 03/15/2023] Open
Abstract
The enzyme 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) is an intermediate enzyme in triglyceride synthesis. The aim was to study the regulatory mechanism of AGPAT2 on Nile tilapia, Oreochromis niloticus. In this study, antisense RNA technology was used to knock-down AGPAT2 in Nile tilapia. Compared with the control groups (transfected with ultrapure water or the blank expression vector), the AGPAT2 knock-down group showed a significantly higher weight gain rate, special growth rate, visceral somatic index, and hepatopancreas somatic index; and significantly increased the total cholesterol, triglycerides, glucose, low-density lipoprotein cholesterol, and insulin levels in serum. In addition, the contents of total cholesterol and triglycerides and the abundance of superoxide dismutase, catalase, and glutathione peroxidase in the liver significantly increased, while the malondialdehyde content significantly decreased. The liver cells became severely vacuolated and accumulated lipids in the AGPAT2 knock-down group. Comparative transcriptome analyses (AGPAT2 knock-down vs. control group) revealed 1789 differentially expressed genes (DEGs), including 472 upregulated genes and 1313 downregulated genes in the AGPAT2 knock-down group. Functional analysis showed that the main pathway of differentially expressed genes enrichment was lipid metabolism and oxidative stress, such as steroid biosynthesis, unsaturated fatty acid biosynthesis, the PPAR signaling pathway, and the P53 pathway. We used qRT-PCR to verify the mRNA expression changes of 13 downstream differential genes in related signaling pathways. These findings demonstrate that knock-down of AGPAT2 in tilapia leads to abnormal lipid metabolism and oxidative stress.
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Affiliation(s)
- Tiantian Feng
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China
| | - Yifan Tao
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Freshwater Fisheries Research Center, Ministry of Agriculture and Rural Affairs, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Yue Yan
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
| | - Siqi Lu
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Freshwater Fisheries Research Center, Ministry of Agriculture and Rural Affairs, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Yan Li
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Freshwater Fisheries Research Center, Ministry of Agriculture and Rural Affairs, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Xing Zhang
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China
| | - Jun Qiang
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Freshwater Fisheries Research Center, Ministry of Agriculture and Rural Affairs, Chinese Academy of Fishery Sciences, Wuxi 214081, China
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
- Correspondence:
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Schietgat L, Cuissart B, De Grave K, Efthymiadis K, Bureau R, Crémilleux B, Ramon J, Lepailleur A. Automated detection of toxicophores and prediction of mutagenicity using PMCSFG algorithm. Mol Inform 2023; 42:e2200232. [PMID: 36529710 DOI: 10.1002/minf.202200232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 12/13/2022] [Accepted: 12/18/2022] [Indexed: 12/23/2022]
Abstract
Maximum common substructures (MCS) have received a lot of attention in the chemoinformatics community. They are typically used as a similarity measure between molecules, showing high predictive performance when used in classification tasks, while being easily explainable substructures. In the present work, we applied the Pairwise Maximum Common Subgraph Feature Generation (PMCSFG) algorithm to automatically detect toxicophores (structural alerts) and to compute fingerprints based on MCS. We present a comparison between our MCS-based fingerprints and 12 well-known chemical fingerprints when used as features in machine learning models. We provide an experimental evaluation and discuss the usefulness of the different methods on mutagenicity data. The features generated by the MCS method have a state-of-the-art performance when predicting mutagenicity, while they are more interpretable than the traditional chemical fingerprints.
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Affiliation(s)
- Leander Schietgat
- Artificial Intelligence Lab, Vrije Universiteit Brussel, Brussel, Belgium.,Department of Computer Science, KU Leuven, Leuven, Belgium
| | - Bertrand Cuissart
- Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen, UNICAEN, ENSICAEN, CNRS - UMR GREYC, Normandie Univ., Caen, France
| | | | | | - Ronan Bureau
- Centre d'Etudes et de Recherche sur le Médicament de Normandie, UNICAEN, CERMN, Normandie Univ., Caen, France
| | - Bruno Crémilleux
- Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen, UNICAEN, ENSICAEN, CNRS - UMR GREYC, Normandie Univ., Caen, France
| | - Jan Ramon
- INRIA Lille Nord Europe, Lille, France
| | - Alban Lepailleur
- Centre d'Etudes et de Recherche sur le Médicament de Normandie, UNICAEN, CERMN, Normandie Univ., Caen, France
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Santibáñez-Andrade M, Quezada-Maldonado EM, Rivera-Pineda A, Chirino YI, García-Cuellar CM, Sánchez-Pérez Y. The Road to Malignant Cell Transformation after Particulate Matter Exposure: From Oxidative Stress to Genotoxicity. Int J Mol Sci 2023; 24:ijms24021782. [PMID: 36675297 PMCID: PMC9860989 DOI: 10.3390/ijms24021782] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 12/31/2022] [Accepted: 01/06/2023] [Indexed: 01/17/2023] Open
Abstract
In cells, oxidative stress is an imbalance between the production/accumulation of oxidants and the ability of the antioxidant system to detoxify these reactive products. Reactive oxygen species (ROS), cause multiple cellular damages through their interaction with biomolecules such as lipids, proteins, and DNA. Genotoxic damage caused by oxidative stress has become relevant since it can lead to mutation and play a central role in malignant transformation. The evidence describes chronic oxidative stress as an important factor implicated in all stages of the multistep carcinogenic process: initiation, promotion, and progression. In recent years, ambient air pollution by particulate matter (PM) has been cataloged as a cancer risk factor, increasing the incidence of different types of tumors. Epidemiological and toxicological evidence shows how PM-induced oxidative stress could mediate multiple events oriented to carcinogenesis, such as proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, and activation of invasion/metastasis pathways. In this review, we summarize the findings regarding the involvement of oxidative and genotoxic mechanisms generated by PM in malignant cell transformation. We also discuss the importance of new approaches oriented to studying the development of tumors associated with PM with more accuracy, pursuing the goal of weighing the impact of oxidative stress and genotoxicity as one of the main mechanisms associated with its carcinogenic potential.
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Affiliation(s)
- Miguel Santibáñez-Andrade
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología, San Fernando No. 22, Tlalpan, México City CP 14080, Mexico
| | - Ericka Marel Quezada-Maldonado
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología, San Fernando No. 22, Tlalpan, México City CP 14080, Mexico
| | - Andrea Rivera-Pineda
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología, San Fernando No. 22, Tlalpan, México City CP 14080, Mexico
- Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Av. IPN No. 2508 Col. San Pedro Zacatenco, México City CP 07360, Mexico
| | - Yolanda I. Chirino
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Reyes Iztacala, Tlalnepantla CP 54090, Mexico
| | - Claudia M. García-Cuellar
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología, San Fernando No. 22, Tlalpan, México City CP 14080, Mexico
- Correspondence: (C.M.G.-C.); (Y.S.-P.); Tel.: +52-(55)-3693-5200 (ext. 209) (Y.S.-P.)
| | - Yesennia Sánchez-Pérez
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología, San Fernando No. 22, Tlalpan, México City CP 14080, Mexico
- Correspondence: (C.M.G.-C.); (Y.S.-P.); Tel.: +52-(55)-3693-5200 (ext. 209) (Y.S.-P.)
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45
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Martemucci G, Portincasa P, Centonze V, Mariano M, Khalil M, D'Alessandro AG. Prevention of Oxidative Stress and Diseases by Antioxidant Supplementation. Med Chem 2023; 19:509-537. [PMID: 36453505 DOI: 10.2174/1573406419666221130162512] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 09/02/2022] [Accepted: 09/27/2022] [Indexed: 12/03/2022]
Abstract
Excessive and uncontrolled oxidative stress can damage biomacromolecules, such as lipids, proteins, carbohydrates, and DNA, by free radical and oxidant overproduction. In this review, we critically discuss the main properties of free radicals, their implications in oxidative stress, and specific pathological conditions. In clinical medicine, oxidative stress can play a role in several chronic noncommunicable diseases, such as diabetes mellitus, cardiovascular, inflammatory, neurodegenerative diseases, and tumours. Antioxidant supplements can theoretically prevent or stop the progression of diseases, but a careful literature analysis finds that more evidence is needed to dissect the ultimate beneficial effect of antioxidants versus reactive oxygen species in several diseases.
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Affiliation(s)
- Giovanni Martemucci
- Department of Agricultural and Environmental Sciences, University of Bari Aldo Moro, Via G. Amendola, 165/A - 70126 Bari, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Vincenzo Centonze
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Michele Mariano
- Unità Operativa Complessa di Radiodiagnostica Universitaria, Policlinico di Bari, Piazza Giulio Cesare, 11, 70124 Bari, Italy
| | - Mohamad Khalil
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Angela Gabriella D'Alessandro
- Department of Agricultural and Environmental Sciences, University of Bari Aldo Moro, Via G. Amendola, 165/A - 70126 Bari, Italy
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Yu J, Zheng C, Zheng J, Duan G, Guo Q, Zhang P, Wan M, Duan Y. Development of Intestinal Injury and Restoration of Weaned Piglets under Chronic Immune Stress. Antioxidants (Basel) 2022; 11:antiox11112215. [PMID: 36358587 PMCID: PMC9686571 DOI: 10.3390/antiox11112215] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 11/04/2022] [Accepted: 11/07/2022] [Indexed: 11/11/2022] Open
Abstract
This study aimed to investigate the effects of lipopolysaccharide (LPS)-induced chronic immune stress on intestinal morphology and function, immune system, oxidative status, and mitochondrial function in piglets. Fifty healthy Duroc × Landrace × Yorkshire piglets (21 ± 2 days old, barrow, 6.98 ± 0.14 kg body weight) were selected and randomly allotted to five groups, which were slaughtered at 0 (0 group), 1, 5, 9, and 15 d of LPS injection. The results showed that compared with the piglets without LPS injection, LPS injection significantly impaired the intestinal morphology and permeability at 1, 5, and 9 d, as manifested by the increased serum lactic acid and decreased ratio of villus height to crypt depth (p < 0.05). Moreover, intestinal inflammation and oxidative and mitochondrial injury were caused at 1 d, as manifested by upregulated IL-6 mRNA expression, increased malondialdehyde content, and impaired mitochondrial morphology (p < 0.05). However, these parameters were restored to levels identical to 0 group at 9~15 d, accompanied by significantly increased antioxidant capacity, enhanced protein expression of CD3+ and CD68+, and upregulated mRNA abundance of genes related to mitochondrial biogenesis and functions (p < 0.05). Collectively, these results suggest that the intestinal injury of piglets caused by chronic immune stress could be self-repaired.
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Affiliation(s)
- Jiayi Yu
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences; Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, China
- University of Chinese Academy of Sciences, Beijing 100039, China
| | - Changbing Zheng
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Jie Zheng
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences; Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, China
- University of Chinese Academy of Sciences, Beijing 100039, China
| | - Geyan Duan
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences; Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, China
- University of Chinese Academy of Sciences, Beijing 100039, China
| | - Qiuping Guo
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences; Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, China
| | - Peiwen Zhang
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Mengliao Wan
- College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Yehui Duan
- CAS Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences; Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha 410125, China
- University of Chinese Academy of Sciences, Beijing 100039, China
- Correspondence: ; Tel.: +86-0731-8461-9767
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Gonon G, de Toledo SM, Perumal V, Jay-Gerin JP, Azzam EI. Impact of the redox environment on propagation of radiation bystander effects: The modulating effect of oxidative metabolism and oxygen partial pressure. MUTATION RESEARCH. GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2022; 883-884:503559. [PMID: 36462795 DOI: 10.1016/j.mrgentox.2022.503559] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/09/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022]
Abstract
Redox modulated pathways play important roles in out-of-field effects of ionizing radiation. We investigated how the redox environment impacts the magnitude of propagation of stressful effects from irradiated to bystander cells. Normal human fibroblasts that have incorporated [3H]-thymidine were intimately co-cultured with bystander cells in a strategy that allowed isolation of bystander cells with high purity. The antioxidant glutathione peroxidase (GPX) was maintained either at wild-type conditions or overexpressed in the bystanders. Following 24 h of coculture, levels of stress-responsive p21Waf1, p-Hdm2, and connexin43 proteins were increased in bystander cells expressing wild-type GPX relative to respective controls. These levels were significantly attenuated when GPX was ectopically overexpressed, demonstrating by direct approach the involvement of a regulator of intracellular redox homeostasis. Evidence of participation of pro-oxidant compounds was generated by exposing confluent cell cultures to low fluences of 3.7 MeV α particles in presence or absence of t-butyl hydroperoxide. By 3 h post-exposure to fluences wherein only ∼2% of cells are traversed through the nucleus by a particle track, increases in chromosomal damage were greater than expected in absence of the drug (p < 0.001) and further enhanced in its presence (p < 0.05). While maintenance and irradiation of cell cultures at low oxygen pressure (pO2 3.8 mm Hg) to mimic in vivo still supported the participation of bystander cells in responses assessed by chromosomal damage and stress-responsive protein levels (p < 0.001), the effects were attenuated compared to ambient pO2 (155 mm Hg) (p < 0.05). Together, the results show that bystander effects are attenuated at below ambient pO2 and when metabolic oxidative stress is reduced but increased when the basal redox environment tilts towards oxidizing conditions. They are consistent with bystander effects being independent of radiation dose rate.
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Affiliation(s)
- Géraldine Gonon
- Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SERAMED/LRAcc, Fontenay-aux-Roses, France; Department of Radiology, Rutgers New Jersey Medical School, Newark, NJ, USA.
| | - Sonia M de Toledo
- Department of Radiology, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Venkatachalam Perumal
- Department of Radiology, Rutgers New Jersey Medical School, Newark, NJ, USA; Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India
| | - Jean-Paul Jay-Gerin
- Département de médecine nucléaire et de radiobiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada
| | - Edouard I Azzam
- Department of Radiology, Rutgers New Jersey Medical School, Newark, NJ, USA; Radiobiology and Health Branch, Isotopes, Radiobiology & Environment Directorate (IRED), Canadian Nuclear Laboratories (CNL), Chalk River, Ontario, Canada.
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Ramírez-Patiño R, Avalos-Navarro G, Figuera LE, Varela-Hernández JJ, Bautista-Herrera LA, Muñoz-Valle JF, Gallegos-Arreola MP. Influence of nitric oxide signaling mechanisms in cancer. Int J Immunopathol Pharmacol 2022; 36:3946320221135454. [PMID: 36260949 PMCID: PMC9585559 DOI: 10.1177/03946320221135454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Nitric oxide (NO) is a molecule with multiple biological functions that is involved in various pathophysiological processes such as neurotransmission and blood vessel relaxation as well as the endocrine system, immune system, growth factors, and cancer. However, in the carcinogenesis process, it has a dual behavior; at low doses, NO regulates homeostatic functions, while at high concentrations, it promotes tissue damage or acts as an agent for immune defense against microorganisms. Thus, its participation in the carcinogenic process is controversial. Cancer is a multifactorial disease that presents complex behavior. A better understanding of the molecular mechanisms associated with the initiation, promotion, and progression of neoplastic processes is required. Some hypotheses have been proposed regarding the influence of NO in activating oncogenic pathways that trigger carcinogenic processes, because NO might regulate some signaling pathways thought to promote cancer development and more aggressive tumor growth. Additionally, NO inhibits apoptosis of tumor cells, together with the deregulation of proteins that are involved in tissue homeostasis, promoting spreading to other organs and initiating metastatic processes. This paper describes the signaling pathways that are associated with cancer, and how the concentration of NO can serve a beneficial or pathological function in the initiation and promotion of neoplastic events.
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Affiliation(s)
- R Ramírez-Patiño
- Departamento de Ciencias Médicas y de la Vida, Centro Universitario de la Ciénega (CUCIÉNEGA), Universidad de Guadalajara, Ocotlán Jalisco, México
| | - G Avalos-Navarro
- Departamento de Ciencias Médicas y de la Vida, Centro Universitario de la Ciénega (CUCIÉNEGA), Universidad de Guadalajara, Ocotlán Jalisco, México
| | - LE Figuera
- División de Génetica, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara Jalisco, México,Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara Jalisco, México
| | - JJ Varela-Hernández
- Departamento de Ciencias Médicas y de la Vida, Centro Universitario de la Ciénega (CUCIÉNEGA), Universidad de Guadalajara, Ocotlán Jalisco, México
| | - LA Bautista-Herrera
- Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingeniería (CUCEI), Universidad de Guadalajara, Guadalajara Jalisco, México
| | - JF Muñoz-Valle
- Instituto de Investigación en Ciencias Biomédicas (IICB), Centro Universitario de Ciencias de la Salud (CUCS) Universidad de Guadalajara, Guadalajara Jalisco, México
| | - MP Gallegos-Arreola
- División de Génetica, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara Jalisco, México,Martha Patricia Gallegos-Arreola, División de Genética CIBO, IMSS, Sierra Mojada 800, Col, Independencia, Guadalajara, Jalisco 44340, México.
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Chedea VS, Macovei ȘO, Bocsan IC, Măgureanu DC, Levai AM, Buzoianu AD, Pop RM. Grape Pomace Polyphenols as a Source of Compounds for Management of Oxidative Stress and Inflammation—A Possible Alternative for Non-Steroidal Anti-Inflammatory Drugs? Molecules 2022; 27:molecules27206826. [PMID: 36296420 PMCID: PMC9612310 DOI: 10.3390/molecules27206826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/05/2022] [Accepted: 10/09/2022] [Indexed: 11/25/2022] Open
Abstract
Flavonoids, stilbenes, lignans, and phenolic acids, classes of polyphenols found in grape pomace (GP), were investigated as an important alternative source for active substances that could be used in the management of oxidative stress and inflammation. The benefic antioxidant and anti-inflammatory actions of GP are presented in the literature, but they are derived from a large variety of experimental in vitro and in vivo settings. In these in vitro works, the decrease in reactive oxygen species, malondialdehyde, and thiobarbituric acid reactive substances levels and the increase in glutathione levels show the antioxidant effects. The inhibition of nuclear factor kappa B and prostaglandin E2 inflammatory pathways and the decrease of some inflammatory markers such as interleukin-8 (IL-8) demonstrate the anti-inflammatory actions of GP polyphenols. The in vivo studies further confirmed the antioxidant (increase in catalase, superoxide dismutase and glutathione peroxidase levels and a stimulation of endothelial nitric oxide synthase -eNOS gene expression) and anti-inflammatory (inhibition of IL-1𝛼, IL-1β, IL-6, interferon-𝛾, TNF-α and C-reactive protein release) activities. Grape pomace as a whole extract, but also different individual polyphenols that are contained in GP can modulate the endogenous pathway responsible in reducing oxidative stress and chronic inflammation. The present review analyzed the effects of GP in oxidative stress and inflammation, suggesting that it could become a valuable therapeutic candidate capable to reduce the aforementioned pathological processes. Grape pomace extract could become an adjuvant treatment in the attempt to reduce the side effects of the classical anti-inflammatory medication like non-steroidal anti-inflammatory drugs (NSAIDs).
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Affiliation(s)
- Veronica Sanda Chedea
- Research Department, Research Station for Viticulture and Enology Blaj (SCDVV Blaj), 515400 Blaj, Romania
| | - Ștefan Octavian Macovei
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Ioana Corina Bocsan
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, No. 23, Marinescu Street, 400012 Cluj Napoca, Romania
- Correspondence:
| | - Dan Claudiu Măgureanu
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Antonia Mihaela Levai
- Department Mother and Child, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, No. 3–5, Clinicilor Street, 400012 Cluj Napoca, Romania
| | - Anca Dana Buzoianu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, No. 23, Marinescu Street, 400012 Cluj Napoca, Romania
| | - Raluca Maria Pop
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, No. 23, Marinescu Street, 400012 Cluj Napoca, Romania
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Xia Y, Wang D, Li J, Chen M, Wang D, Jiang Z, Liu B. Compounds purified from edible fungi fight against chronic inflammation through oxidative stress regulation. Front Pharmacol 2022; 13:974794. [PMID: 36160418 PMCID: PMC9500316 DOI: 10.3389/fphar.2022.974794] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/17/2022] [Indexed: 01/24/2023] Open
Abstract
Chronic inflammation is associated with various chronic diseases, including cardiovascular disease, neurodegenerative disease, and cancer, which severely affect the health and quality of life of people. Oxidative stress induced by unbalanced production and elimination of reactive oxygen species (ROS) is one of the essential risk factors for chronic inflammation. Recent studies, including the studies of mushrooms, which have received considerable attention, report that the antioxidant effects of natural compounds have more advantages than synthetic antioxidants. Mushrooms have been consumed by humans as precious nourishment for 3,000 years, and so far, more than 350 types have been identified in China. Mushrooms are rich in polysaccharides, peptides, polyphenols, alkaloids, and terpenoids and are associated with several healthy biological functions, especially antioxidant properties. As such, the extracts purified from mushrooms could activate the expression of antioxidant enzymes through the Keap1/Nrf2/ARE pathway to neutralize excessive ROS and inhibit ROS-induced chronic inflammation through the NF-κB pathway. Recently, the antioxidant properties of mushrooms have been successfully applied to treating cardiovascular disease (CAD), neurodegenerative diseases, diabetes mellitus, and cancer. The present review summarizes the antioxidant properties and the mechanism of compounds purified from mushrooms, emphasizing the oxidative stress regulation of mushrooms to fight against chronic inflammation.
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Affiliation(s)
- Yidan Xia
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Dongxu Wang
- Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, China
| | - Jiaqi Li
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Minqi Chen
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Duo Wang
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Ziping Jiang
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China,*Correspondence: Ziping Jiang, ; Bin Liu,
| | - Bin Liu
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China,*Correspondence: Ziping Jiang, ; Bin Liu,
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