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Gulcin İ. Antioxidants: a comprehensive review. Arch Toxicol 2025:10.1007/s00204-025-03997-2. [PMID: 40232392 DOI: 10.1007/s00204-025-03997-2] [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: 01/31/2025] [Accepted: 02/18/2025] [Indexed: 04/16/2025]
Abstract
Antioxidants had a growing interest owing to their protective roles in food and pharmaceutical products against oxidative deterioration and in the body and against oxidative stress-mediated pathological processes. Screening of antioxidant properties of plants and plant derived compounds requires appropriate methods, which address the mechanism of antioxidant activity and focus on the kinetics of the reactions including the antioxidants. Many studies have been conducted with evaluating antioxidant activity of various samples of research interest using by different methods in food and human health. These methods were classified methods described and discussed in this review. Methods based on inhibited autoxidation are the most suited for termination-enhancing antioxidants and, for chain-breaking antioxidants while different specific studies are needed for preventive antioxidants. For this purpose, the most commonly methods used in vitro determination of antioxidant capacity of food and pharmaceutical constituents are examined and also a selection of chemical testing methods is critically reviewed and highlighting. In addition, their advantages, disadvantages, limitations and usefulness were discussed and investigated for pure molecules and raw plant extracts. The effect and influence of the reaction medium on performance of antioxidants is also addressed. Hence, this overview provides a basis and rationale for developing standardized antioxidant capacity methods for the food, nutraceuticals, and dietary supplement industries. Also, the most important advantages and shortcomings of each method were detected and highlighted. The underlying chemical principles of these methods have been explained and thoroughly analyzed. The chemical principles of methods of 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical scavenging, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS·+) scavenging, ferric ions (Fe3+) reducing assay, ferric reducing antioxidant power (FRAP) assay, cupric ions (Cu2+) reducing power assay (Cuprac), Folin-Ciocalteu reducing capacity (FCR assay), superoxide radical anion (O2·-), hydroxyl radical (OH·) scavenging, peroxyl radical (ROO·) removing, hydrogen peroxide (H2O2) decomposing, singlet oxygen (1O2) quenching assay, nitric oxide radical (NO·) scavenging assay and chemiluminescence assay are overviewed and critically discussed. Also, the general antioxidant aspects of the main food and pharmaceutical components were discussed through several methods currently used for detecting antioxidant properties of these components. This review consists of two main sections. The first section is devoted to the main components in food and their pharmaceutical applications. The second general section includes definitions of the main antioxidant methods commonly used for determining the antioxidant activity of components. In addition, some chemical, mechanistic, and kinetic properties, as well as technical details of the above mentioned methods, are provided. The general antioxidant aspects of main food components have been discussed through various methods currently used to detect the antioxidant properties of these components.
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Affiliation(s)
- İlhami Gulcin
- Faculty of Sciences, Department of Chemistry, Atatürk University, 25240, Erzurum, Türkiye.
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Lemos I, Freitas-Dias C, Hipólito A, Ramalho J, Carteni F, Gonçalves LG, Mazzoleni S, Serpa J. Cell-Free DNA (cfDNA) Regulates Metabolic Remodeling, Sustaining Proliferation, Quiescence, and Migration in MDA-MB-231, a Triple-Negative Breast Carcinoma (TNBC) Cell Line. Metabolites 2025; 15:227. [PMID: 40278356 PMCID: PMC12029764 DOI: 10.3390/metabo15040227] [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: 02/25/2025] [Revised: 03/11/2025] [Accepted: 03/24/2025] [Indexed: 04/26/2025] Open
Abstract
Background: The clinical relevance of circulating cell-free DNA (cfDNA) in oncology has gained significant attention, with its potential as a biomarker for cancer diagnosis and monitoring. However, its precise role in cancer biology and progression remains unclear. cfDNA in cancer patients' blood has been shown to activate signaling pathways, such as those mediated by toll-like receptors (TLRs), suggesting its involvement in cancer cell adaptation to the tumor microenvironment. Methods: This impact of cfDNA released from MDA-MB-231, a triple-negative breast cancer (TNBC) cell line was assessed, focusing on glucose availability and culture duration. The impact of cfDNA on the proliferation of MDA-MB-231 cells was investigated using proliferation curves, while cellular migration was evaluated through wound healing assays. The metabolic alterations induced by distinct cfDNA variants in MDA-MB-231 cells were investigated through nuclear magnetic resonance (NMR) spectroscopy, and their effect on cisplatin resistance was evaluated using flow cytometry. Furthermore, the expression levels of DNA-sensitive Toll-like receptor 9 (TLR9) were quantified via immunofluorescence, alongside its colocalization with lysosome-associated membrane protein 1 (LAMP1). Results: This study indicates that cfDNA facilitates metabolic adaptation, particularly under metabolic stress, by modulating glucose and glutamine consumption, key pathways in tumor cell metabolism. Exposure to cfDNA induced distinct metabolic shifts, favoring energy production through oxidative phosphorylation. The anti-cancer activity of cfDNA isolated from conditioned media of cells cultured under stressful conditions is influenced by the culture duration, emphasizing the importance of adaptation and se-lection in releasing cfDNA that can drive pro-tumoral processes. Additionally, cfDNA exposure influenced cell proliferation, quiescence, and migration, processes linked to metastasis and treatment resistance. These findings underscore cfDNA as a key mediator of metabolic reprogramming and adaptive responses in cancer cells, contributing to tumor progression and therapy resistance. Furthermore, the activation of TLR9 signaling suggests a mechanistic basis for cfDNA-induced phenotypic changes. Conclusions: Overall, cfDNA serves as a crucial signaling molecule in the tumor microenvironment, orchestrating adaptive processes that enhance cancer cell survival and progression.
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Affiliation(s)
- Isabel Lemos
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisbon, Portugal; (I.L.); (C.F.-D.); (A.H.); (J.R.)
- Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisbon, Portugal
| | - Catarina Freitas-Dias
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisbon, Portugal; (I.L.); (C.F.-D.); (A.H.); (J.R.)
- Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisbon, Portugal
| | - Ana Hipólito
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisbon, Portugal; (I.L.); (C.F.-D.); (A.H.); (J.R.)
- Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisbon, Portugal
| | - José Ramalho
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisbon, Portugal; (I.L.); (C.F.-D.); (A.H.); (J.R.)
| | - Fabrizio Carteni
- Lab Applied Ecology and System Dynamics, Dipartimento di Agraria, Università di Napoli “Federico II”, Portici, 80055 Naples, Italy; (F.C.); (S.M.)
| | - Luís G. Gonçalves
- Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA), Avenida da República (EAN), 2780-157 Oeiras, Portugal;
| | - Stefano Mazzoleni
- Lab Applied Ecology and System Dynamics, Dipartimento di Agraria, Università di Napoli “Federico II”, Portici, 80055 Naples, Italy; (F.C.); (S.M.)
| | - Jacinta Serpa
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisbon, Portugal; (I.L.); (C.F.-D.); (A.H.); (J.R.)
- Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023 Lisbon, Portugal
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Manhar N, Singh SK, Yadav P, Bishnolia M, Khurana A, Bhatti JS, Navik U. Methyl Donor Ameliorates CCl 4-Induced Nephrotoxicity by Inhibiting Oxidative Stress, Inflammation, and Fibrosis Through the Attenuation of Kidney Injury Molecule 1 and Neutrophil Gelatinase-Associated Lipocalin Expression. J Biochem Mol Toxicol 2025; 39:e70188. [PMID: 39987517 DOI: 10.1002/jbt.70188] [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: 08/21/2024] [Revised: 01/21/2025] [Accepted: 02/08/2025] [Indexed: 02/25/2025]
Abstract
Carbon tetrachloride (CCl4), a volatile organic compound, is harmful to multi-organs, including the liver, lungs, muscles, and kidneys. Methyl donors, such as methionine, choline, betaine, and folic acid, are vital to one-carbon metabolism and have great potential to alleviate oxidative stress and inflammation, thus mitigating disease onset. Hence, the current study aims to examine the therapeutic effect of methyl donors against CCl4-induced nephrotoxicity. Nephrotoxicity was developed in male Sprague Dawley rats using CCl4 at a dose of 1 mL/kg (4-week model induction) twice a week via the intraperitoneal route. Thereafter, methyl donor treatments through oral gavage were given for the next 6 weeks with a continuation of CCl4 administration. Biochemical, oxidative stress parameters, histopathological, and qRT-PCR analyses were done at the completion of the 10-week. Biochemical analyses revealed that CCl4 induces nephrotoxicity, as evidenced by increased urea and creatinine levels and decreased albumin levels. These detrimental effects were significantly ameliorated by methyl donor treatment. Moreover, CCl4 decreased the antioxidant enzyme activity (superoxide dismutase; SOD and catalase; CAT) while increasing oxidative stress markers (malondialdehyde; MDA and nitrite). Methyl donor treatment effectively mitigated these oxidative changes. Histopathological analysis demonstrated the nephroprotective effect of methyl donors against CCl4-induced nephrotoxicity, showing reduced tissue damage and protection of renal architecture. At the molecular level, methyl donor treatment alleviated the CCl4-induced increase in kidney injury biomarkers (Kidney injury molecule 1; KIM-1 and Neutrophil gelatinase-associated lipocalin; NGAL), as well as inflammatory (IL-6 and TNF-α) and fibrosis-related genes (Acta-2 and TGF-β). In conclusion, our findings suggest that methyl donors possess anti-inflammatory and anti-fibrotic properties. They protect against CCl4-induced oxidative damage to renal cells, likely due to their reactive oxygen species scavenging capabilities and their ability to restore key early renal injury biomarkers (KIM-1 and NGAL). Methyl donors hold great promise as a cutting-edge therapy approach for preventing CCl4-induced nephrotoxicity.
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Affiliation(s)
- Nirmal Manhar
- Department of Pharmacology, Central University of Punjab, Bathinda, India
| | - Sumeet Kumar Singh
- Department of Pharmacology, Central University of Punjab, Bathinda, India
| | - Poonam Yadav
- Department of Pharmacology, Central University of Punjab, Bathinda, India
| | - Manish Bishnolia
- Department of Pharmacology, Central University of Punjab, Bathinda, India
| | - Amit Khurana
- Department of Pharmacology, Central University of Punjab, Bathinda, India
| | - Jasvinder Singh Bhatti
- Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India
| | - Umashanker Navik
- Department of Pharmacology, Central University of Punjab, Bathinda, India
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Sattanathan G, Padmapriya S, Almanaa TN, Malafaia G, Govindarajan M. Impact of Chaetomorpha aerea-enriched diet on growth, feed utilization, and haemato-immunological responses in Clarias batrachus challenged with Aeromonas hydrophila. Microb Pathog 2024; 196:106962. [PMID: 39303960 DOI: 10.1016/j.micpath.2024.106962] [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: 07/06/2024] [Revised: 09/14/2024] [Accepted: 09/18/2024] [Indexed: 09/22/2024]
Abstract
The bacteria Aeromonas hydrophila, which causes motile Aeromonas septicemia (MAS), is dangerous to aquaculture because it affects the fish's well-being and production. As the aquaculture industry seeks sustainable and effective methods to enhance fish immunity and growth, natural supplements such as marine algae have gained attention. This study explored the potential benefits of incorporating the green marine algae Chaetomorpha aerea into the fish diet, focusing on disease resistance, growth, feed utilization, and hematological and immunological responses. Five diets were prepared, varying concentrations of C. aerea (0 control, T1: 1 g/kg; T2: 2 g/kg: T3: 5 g/kg: and T4: 10 g/kg) and administered to fish over 30 days. Following the feeding trial, the fish were exposed to A. hydrophila, and their survival rates were observed for the next 14 days. The findings demonstrated that the final weight, weight gain, relative growth rate, specific growth rate, and daily growth rate were all positively impacted by a diet containing 5 g/kg of C. aerea. Additionally, fish in the 5 g/kg C. aerea group demonstrated improved feed conversion efficiency compared to the control group. While there were no significant changes in red and white blood cell counts on the initial day, serum lysozyme activity and overall resistance to infection were enhanced in fish receiving C. aerea at 2 and 5 g/kg. These results imply that C. aerea supplementation with fish supplements may be a useful immunostimulant, boosting improved health and growth in sustainable aquaculture practices.
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Affiliation(s)
- Govindharajan Sattanathan
- Key Laboratory of Biochemistry and Molecular Biology in Universities of Shandong (Weifang University), Wei-fang Key Laboratory of Coho Salmon Culturing Facility Engineering, Institute of Modern Facility Fisheries, College of Biology and Oceanography, Weifang University, Weifang, 261061, China
| | - Swaminathan Padmapriya
- Department of Zoology, Government College for Women (Autonomous), Kumbakonam, 612 001, Tamil Nadu, India
| | - Taghreed N Almanaa
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
| | - Guilherme Malafaia
- Post-Graduation Program in Ecology, Conservation, and Biodiversity, Federal University of Uberlândia, Uberlândia, MG, Brazil; Laboratory of Toxicology Applied to the Environment, Goiano Federal Institute, Urutaí Campus. Rodovia Geraldo Silva Nascimento, 2,5 km, Zona Rural, Urutaí, GO, Brazil; Post-Graduation Program in Biotechnology and Biodiversity, Federal University of Goiás, Goiânia, GO, Brazil; Post-Graduation Program in Conservation of Cerrado Natural Resources, Goiano Federal Institute, Urutaí, GO, Brazil
| | - Marimuthu Govindarajan
- Department of Zoology, Government College for Women (Autonomous), Kumbakonam, 612 001, Tamil Nadu, India; Unit of Vector Control, Phytochemistry and Nanotechnology, Department of Zoology, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India.
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Rahayu I, Arfian N, Kustanti CY, Wahyuningsih MSH. The effectiveness of antioxidant agents in delaying progression of diabetic nephropathy: A systematic review of randomized controlled trials. BIOIMPACTS : BI 2024; 15:30129. [PMID: 39963561 PMCID: PMC11830129 DOI: 10.34172/bi.30129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 02/16/2024] [Accepted: 02/28/2024] [Indexed: 02/20/2025]
Abstract
Introduction Oxidative stress plays a central role in the pathophysiology of diabetes mellitus and its complications, including diabetic nephropathy. Excessive production of reactive oxygen species (ROS) alters renal metabolic pathways, leading to inflammation, endothelial dysfunction, and fibrosis, ultimately resulting in end-stage renal disease (ESRD). Studies have shown that exogenous antioxidants can improve the pathophysiological condition of patients with diabetic nephropathy. Objective: This systematic review aims to investigate the types of antioxidant agents that inhibit the development of diabetic nephropathy and the effectiveness of antioxidant agent interventions to repair kidney structure and function. Methods A systematic review of randomized controlled trials that examined the role of antioxidants in improving diabetic nephropathy was conducted. The literature search was performed on PubMed, ScienceDirect, and EBSCO. The inclusion criteria covered articles on the antioxidant activity of herbal extracts and compounds that inhibit the progression of diabetic nephropathy in humans. In addition, the articles were written in English and published between 2012 and 2022. The reporting of the systematic review followed the Preferred Reporting Elements for Systematic Review and Meta-Analysis (PRISMA) guideline. The full texts of all potentially relevant systematic reviews were assessed for quality using the Risk of Bias 2 (RoB 2) tool. Results A total of 2,367 articles were identified in the three databases, of which only 15 articles met the inclusion criteria. Antioxidant agents that inhibit diabetic nephropathy can be classified as single antioxidants (silymarin, baicalin, epigallocatechin gallate, vitamin E, selenium, curcumin, α-lipoic acid, and tocotrienol-rich vitamin E) and combined antioxidants (α-lipoic acid with vitamin B6, and resveratrol with losartan). Antioxidant agents have been shown to reduce oxidative stress and inflammation, but their role in the progression of fibrosis remains unclear. The oxidative stress marker MDA was significantly reduced by silymarin, curcumin, vitamin E, tocotrienol-rich vitamin E, selenium, ALA, vitamin B, resveratrol and losartan. Silymarin was found to be the most effective (-3.43 µmol/L; 6.02 to 0.83). Compared to silymarin and epigallocatechin gallate, vitamin E was more effective (at -35.4 ng/L; P < 0.001) in reducing inflammation by decreasing TNF-α levels. In addition, tocotrienol-rich vitamin E, silymarin, baicalin, and selenium showed a decrease TGF-β levels, but did not show statistically significant differences between the placebo and intervention groups. Conclusion Potential antioxidant agents, such as flavonoids, vitamins, fatty acids, and antioxidant minerals, were examined in this systematic review. These agents contribute to reducing markers of oxidative stress and hyperglycemia-induced inflammation. Although several antioxidants play a role in reducing fibrosis markers, the effect does not appear to be statistically significant.
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Affiliation(s)
- Ika Rahayu
- Doctoral Program of Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
- Department of Biochemistry, Faculty of Medicine and Health Sciences, Universitas Kristen Krida Wacana, Jakarta, Indonesia
| | - Nur Arfian
- Department of Anatomy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
- Center for Herbal Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Christina Yeni Kustanti
- Sekolah Tinggi Ilmu Kesehatan Bethesda Yakkum, Yogyakarta, Indonesia
- Lotus Care, Private Clinic for Wound and Palliative Care, Homecare, Yogyakarta, Indonesia
| | - Mae Sri Hartati Wahyuningsih
- Center for Herbal Medicine, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
- Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
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Yamaguchi Y, Sugiki M, Shimizu M, Ogawa K, Kumagai H. Comparative analysis of isothiocyanates in eight cruciferous vegetables and evaluation of the hepatoprotective effects of 4-(methylsulfinyl)-3-butenyl isothiocyanate (sulforaphene) from daikon radish ( Raphanus sativus L.) sprouts. Food Funct 2024; 15:4894-4904. [PMID: 38597802 DOI: 10.1039/d4fo00133h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
The contributions of cruciferous vegetables to human health are widely recognised, particularly at the molecular level, where their isothiocyanates play a significant role. However, compared to the well-studied isothiocyanate 4-(methylsulfinyl)butyl isothiocyanate (sulforaphane) produced from broccoli sprouts, less is known about the pharmacological effects of other isothiocyanates and the stage of vegetables preferable to obtain their benefits. We analysed the quantity and quality of isothiocyanates produced in both the sprouts and mature stages of eight cruciferous vegetables using gas chromatography-mass spectrometry (GC-MS). Additionally, we investigated the hepatoprotective effects of isothiocyanates in a mouse model of acute hepatitis induced by carbon tetrachloride (CCl4). Furthermore, we explored the detoxification enzyme-inducing activities of crude sprout extracts in normal rats. Among the eight cruciferous vegetables, daikon radish (Raphanus sativus L.) sprouts produced the highest amount of isothiocyanates, with 4-(methylsulfinyl)-3-butenyl isothiocyanate (sulforaphene) being the dominant compound. The amount of sulforaphene in daikon radish sprouts was approximately 30 times that of sulforaphane in broccoli sprouts. Sulforaphene demonstrated hepatoprotective effects similar to sulforaphane in ameliorating CCl4-induced hepatic injury in mice. A crude extract of 3-day-old daikon radish sprouts upregulated the detoxifying enzyme glutathione S-transferase (GST) in the liver, whereas the crude extract of broccoli sprouts showed limited upregulation. This study highlights that daikon radish sprouts and sulforaphene have the potential to serve as functional food materials with hepatoprotective effects. Furthermore, daikon radish sprouts may exhibit more potent hepatoprotective effects compared to broccoli sprouts.
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Affiliation(s)
- Yusuke Yamaguchi
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
| | - Mikio Sugiki
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
| | - Motomi Shimizu
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
| | - Kazuki Ogawa
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
| | - Hitomi Kumagai
- College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
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Stevens ME, Paustenbach DJ, Lockhart NJ, Busboom DE, Deckard BM, Brew DW. The presence of erionite in North American geologies and the estimated mesothelioma potency by region. Inhal Toxicol 2024; 36:158-173. [PMID: 38583132 DOI: 10.1080/08958378.2024.2322496] [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: 11/07/2023] [Accepted: 02/19/2024] [Indexed: 04/08/2024]
Abstract
OBJECTIVE Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers. MATERIALS AND METHODS Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined. RESULTS AND DISCUSSION The model predicted potency factors ranged from 0.19 to 11.25 (average ∼3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor ∼0.5. CONCLUSION The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent).
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Wang H, Cheng W, Hu P, Ling T, Hu C, Chen Y, Zheng Y, Wang J, Zhao T, You Q. Integrative analysis identifies oxidative stress biomarkers in non-alcoholic fatty liver disease via machine learning and weighted gene co-expression network analysis. Front Immunol 2024; 15:1335112. [PMID: 38476236 PMCID: PMC10927810 DOI: 10.3389/fimmu.2024.1335112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 02/08/2024] [Indexed: 03/14/2024] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Given the absence of effective treatments to halt its progression, novel molecular approaches to the NAFLD diagnosis and treatment are of paramount importance. Methods Firstly, we downloaded oxidative stress-related genes from the GeneCards database and retrieved NAFLD-related datasets from the GEO database. Using the Limma R package and WGCNA, we identified differentially expressed genes closely associated with NAFLD. In our study, we identified 31 intersection genes by analyzing the intersection among oxidative stress-related genes, NAFLD-related genes, and genes closely associated with NAFLD as identified through Weighted Gene Co-expression Network Analysis (WGCNA). In a study of 31 intersection genes between NAFLD and Oxidative Stress (OS), we identified three hub genes using three machine learning algorithms: Least Absolute Shrinkage and Selection Operator (LASSO) regression, Support Vector Machine - Recursive Feature Elimination (SVM-RFE), and RandomForest. Subsequently, a nomogram was utilized to predict the incidence of NAFLD. The CIBERSORT algorithm was employed for immune infiltration analysis, single sample Gene Set Enrichment Analysis (ssGSEA) for functional enrichment analysis, and Protein-Protein Interaction (PPI) networks to explore the relationships between the three hub genes and other intersecting genes of NAFLD and OS. The distribution of these three hub genes across six cell clusters was determined using single-cell RNA sequencing. Finally, utilizing relevant data from the Attie Lab Diabetes Database, and liver tissues from NASH mouse model, Western Blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) assays were conducted, this further validated the significant roles of CDKN1B and TFAM in NAFLD. Results In the course of this research, we identified 31 genes with a strong association with oxidative stress in NAFLD. Subsequent machine learning analysis and external validation pinpointed two genes: CDKN1B and TFAM, as demonstrating the closest correlation to oxidative stress in NAFLD. Conclusion This investigation found two hub genes that hold potential as novel targets for the diagnosis and treatment of NAFLD, thereby offering innovative perspectives for its clinical management.
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Affiliation(s)
- Haining Wang
- Medical Center for Digestive Diseases, Department of Geriatrics, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Cheng
- Medical Center for Digestive Diseases, Department of Geriatrics, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ping Hu
- Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China
| | - Tao Ling
- Medical Center for Digestive Diseases, Department of Geriatrics, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chao Hu
- Medical Center for Digestive Diseases, Department of Geriatrics, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yongzhen Chen
- Medical Center for Digestive Diseases, Department of Geriatrics, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yanan Zheng
- Medical Center for Digestive Diseases, Department of Geriatrics, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Junqi Wang
- Department of Medical Oncology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Ting Zhao
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Qiang You
- Medical Center for Digestive Diseases, Department of Geriatrics, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Fanfarillo F, Ferraguti G, Lucarelli M, Francati S, Barbato C, Minni A, Ceccanti M, Tarani L, Petrella C, Fiore M. The Impact of ROS and NGF in the Gliomagenesis and their Emerging Implications in the Glioma Treatment. CNS & NEUROLOGICAL DISORDERS DRUG TARGETS 2024; 23:449-462. [PMID: 37016521 DOI: 10.2174/1871527322666230403105438] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 12/19/2022] [Accepted: 02/01/2023] [Indexed: 04/06/2023]
Abstract
Reactive oxygen species (ROS) are highly reactive molecules derived from molecular oxygen (O2). ROS sources can be endogenous, such as cellular organelles and inflammatory cells, or exogenous, such as ionizing radiation, alcohol, food, tobacco, chemotherapeutical agents and infectious agents. Oxidative stress results in damage of several cellular structures (lipids, proteins, lipoproteins, and DNA) and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging. A large body of studies showed that ROS plays an important role in carcinogenesis. Indeed, increased production of ROS causes accumulation in DNA damage leading to tumorigenesis. Various investigations demonstrated the involvement of ROS in gliomagenesis. The most common type of primary intracranial tumor in adults is represented by glioma. Furthermore, there is growing attention on the role of the Nerve Growth Factor (NGF) in brain tumor pathogenesis. NGF is a growth factor belonging to the family of neurotrophins. It is involved in neuronal differentiation, proliferation and survival. Studies were conducted to investigate NGF pathogenesis's role as a pro- or anti-tumoral factor in brain tumors. It has been observed that NGF can induce both differentiation and proliferation in cells. The involvement of NGF in the pathogenesis of brain tumors leads to the hypothesis of a possible implication of NGF in new therapeutic strategies. Recent studies have focused on the role of neurotrophin receptors as potential targets in glioma therapy. This review provides an updated overview of the role of ROS and NGF in gliomagenesis and their emerging role in glioma treatment.
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Affiliation(s)
| | - Giampiero Ferraguti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Marco Lucarelli
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Silvia Francati
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Antonio Minni
- Department of Sensory Organs, Sapienza University of Rome, Rome, Italy
| | - Mauro Ceccanti
- SITAC, Società Italiana per il Trattamento dell'Alcolismo e le sue Complicanze, Rome, Italy
| | - Luigi Tarani
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, Italy
| | - Carla Petrella
- Institute of Biochemistry and Cell Biology, IBBC-CNR, Rome, Italy
| | - Marco Fiore
- Institute of Biochemistry and Cell Biology, IBBC-CNR, Rome, Italy
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Mitalo NS, Waiganjo NN, Mokua Mose J, Bosire DO, Oula JO, Orina Isaac A, Nyabuga Nyariki J. Coinfection with Schistosoma mansoni Enhances Disease Severity in Human African Trypanosomiasis. J Trop Med 2023; 2023:1063169. [PMID: 37954132 PMCID: PMC10637842 DOI: 10.1155/2023/1063169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 09/29/2023] [Accepted: 10/24/2023] [Indexed: 11/14/2023] Open
Abstract
Introduction Human African trypanosomiasis (HAT) and schistosomiasis are neglected parasitic diseases found in the African continent. This study was conducted to determine how primary infection with Schistosoma mansoni affects HAT disease progression with a secondary infection with Trypanosoma brucei rhodesiense (T.b.r) in a mouse model. Methods Female BALB-c mice (6-8 weeks old) were randomly divided into four groups of 12 mice each. The different groups were infected with Schistosoma mansoni (100 cercariae) and Trypanosoma brucei rhodesiense (5.0 × 104) separately or together. Twenty-one days after infection with T.b.r, mice were sacrificed and samples were collected for analysis. Results The primary infection with S. mansoni significantly enhanced successive infection by the T.b.r; consequently, promoting HAT disease severity and curtailing host survival time. T.b.r-induced impairment of the neurological integrity and breach of the blood-brain barrier were markedly pronounced on coinfection with S. mansoni. Coinfection with S. mansoni and T.b.r resulted in microcytic hypochromic anemia characterized by the suppression of RBCs, hematocrit, hemoglobin, and red cell indices. Moreover, coinfection of the mice with the two parasites resulted in leukocytosis which was accompanied by the elevation of basophils, neutrophils, lymphocytes, monocytes, and eosinophils. More importantly, coinfection resulted in a significant elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, creatinine, urea, and uric acid, which are the markers of liver and kidney damage. Meanwhile, S. mansoni-driven dyslipidemia was significantly enhanced by the coinfection of mice with T.b.r. Moreover, coinfection with S. mansoni and T.b.r led to a strong immune response characterized by a significant increase in serum TNF-α and IFN-γ. T.b.r infection enhanced S. mansoni-induced depletion of cellular-reduced glutathione (GSH) in the brain and liver tissues, indicative of lethal oxidative damage. Similarly, coinfection resulted in a significant rise in nitric oxide (NO) and malondialdehyde (MDA) levels. Conclusion Primary infection with S. mansoni exacerbates disease severity of secondary infection with T.b.r in a mouse model that is associated with harmful inflammatory response, oxidative stress, and organ injury.
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Affiliation(s)
- Nancy S. Mitalo
- Department of Biomedical Science & Technology, Technical University of Kenya, P.O. Box 52428, Nairobi 00200, Kenya
| | - Naomi N. Waiganjo
- Department of Biomedical Science & Technology, Technical University of Kenya, P.O. Box 52428, Nairobi 00200, Kenya
| | - John Mokua Mose
- Department of Biomedical Science & Technology, Technical University of Kenya, P.O. Box 52428, Nairobi 00200, Kenya
| | - David O. Bosire
- Department of Biochemistry and Biotechnology, Technical University of Kenya, P.O. Box 52428, Nairobi 00200, Kenya
| | - James O. Oula
- Department of Biomedical Science & Technology, Technical University of Kenya, P.O. Box 52428, Nairobi 00200, Kenya
| | - Alfred Orina Isaac
- Department of Pharmaceutical Sciences and Technology, Technical University of Kenya, P.O. Box 52428, Nairobi 00200, Kenya
| | - James Nyabuga Nyariki
- Department of Biochemistry and Biotechnology, Technical University of Kenya, P.O. Box 52428, Nairobi 00200, Kenya
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11
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Hassan S, Habashy W, Ghoname M, Elnaggar A. Blood hematology and biochemical of four laying hen strains exposed to acute heat stress. INTERNATIONAL JOURNAL OF BIOMETEOROLOGY 2023; 67:675-686. [PMID: 36853273 DOI: 10.1007/s00484-023-02445-z] [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: 08/20/2022] [Revised: 01/10/2023] [Accepted: 02/19/2023] [Indexed: 06/18/2023]
Abstract
This study is aimed at defining physiological responses to heat stress (HS) in four different lines to better understand the underlying mechanisms of various responses in these genotypes when exposed to heat for a short period. At the age of 30 weeks, 176 laying hens (44 each from the Fayoumi, Golden Sabahia, White Leghorn, and Lohman Brown) were allotted to 2 groups (thermoneutral temperature (26.0 ± 1 °C) and HS (35 ± 1 °C) with relative humidity 55 ± 5% for 6 h/day). Blood samples were collected after 6 h of heat. According to the findings of this study, acute HS increased the concentration of LH in hens by 20.2% while decreasing the concentration of FSH by 4.24. Genotype was found to have a significant effect on blood hematology and most blood biochemical. Significant differences were found between heat stress and genotype in most of the blood parameters. Golden sabahia laying hens had significantly higher WBC, IgY, and LH levels than other groups under HS. The findings of the current study suggested that Lohman Brown was less tolerant to acute HS than another genotype.
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Affiliation(s)
- Saber Hassan
- Department of Animal and Poultry Production, Faculty of Agriculture, Damanhour University, Damanhour, 22511, Egypt
| | - Walid Habashy
- Department of Animal and Poultry Production, Faculty of Agriculture, Damanhour University, Damanhour, 22511, Egypt.
| | - Mennatallah Ghoname
- Department of Animal and Poultry Production, Faculty of Agriculture, Damanhour University, Damanhour, 22511, Egypt
| | - Asmaa Elnaggar
- Department of Animal and Poultry Production, Faculty of Agriculture, Damanhour University, Damanhour, 22511, Egypt
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12
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Tay N, Laakso EL, Schweitzer D, Endersby R, Vetter I, Starobova H. Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients. Front Mol Biosci 2022; 9:1015746. [PMID: 36310587 PMCID: PMC9614173 DOI: 10.3389/fmolb.2022.1015746] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 09/20/2022] [Indexed: 11/22/2022] Open
Abstract
Brain cancer and leukemia are the most common cancers diagnosed in the pediatric population and are often treated with lifesaving chemotherapy. However, chemotherapy causes severe adverse effects and chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and debilitating side effect. CIPN can greatly impair quality of life and increases morbidity of pediatric patients with cancer, with the accompanying symptoms frequently remaining underdiagnosed. Little is known about the incidence of CIPN, its impact on the pediatric population, and the underlying pathophysiological mechanisms, as most existing information stems from studies in animal models or adult cancer patients. Herein, we aim to provide an understanding of CIPN in the pediatric population and focus on the 6 main substance groups that frequently cause CIPN, namely the vinca alkaloids (vincristine), platinum-based antineoplastics (cisplatin, carboplatin and oxaliplatin), taxanes (paclitaxel and docetaxel), epothilones (ixabepilone), proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide). We discuss the clinical manifestations, assessments and diagnostic tools, as well as risk factors, pathophysiological processes and current pharmacological and non-pharmacological approaches for the prevention and treatment of CIPN.
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Affiliation(s)
- Nicolette Tay
- Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia
| | - E-Liisa Laakso
- Mater Research Institute-The University of Queensland, South Brisbane, QLD, Australia
| | - Daniel Schweitzer
- Mater Research Institute-The University of Queensland, South Brisbane, QLD, Australia
| | - Raelene Endersby
- Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia
| | - Irina Vetter
- Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia
- The School of Pharmacy, The University of Queensland, Woolloongabba, QLD, Australia
| | - Hana Starobova
- Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia
- *Correspondence: Hana Starobova,
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Halliwell B. Reflections of an Aging Free Radical Part 2: Meeting Inspirational People. Antioxid Redox Signal 2022; 38:792-802. [PMID: 35651275 DOI: 10.1089/ars.2022.0070] [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] [Indexed: 11/12/2022]
Abstract
Significance: During my long career in the field of redox biology, I met many inspiring people, especially Lester Packer. Recent Advances: This special issue of Antioxidants & Redox Signaling is dedicated to Lester Packer. Critical Issues: In this short review, I explore how Lester and other pioneers helped to develop the redox biology field and how I interacted with them. Future Directions: In our research to advance the field of redox biology, we stand on the shoulders of giants, including Lester Packer.
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Affiliation(s)
- Barry Halliwell
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
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14
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Meka Farid Babu, A.R. S, Benerji G.V.. 3-Nitrotyrosine (NT) levels in serum and its association with insulin resistance in patients with type 2 diabetes mellitus: Biomarker role of NT in the assessment of oxidative stress mediated impending vascular complications in nephropathy. Biomedicine (Taipei) 2022. [DOI: 10.51248/.v42i4.1433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Introduction and Aim: 3-Nitrotyrosine (NT) has been recognized as a marker of oxidative stress in diabetes mellitus. NT has also been studied in diverse metabolic conditions. The aim of our study was oriented towards the role of NT as a predictor of oxidative stress mediated impending nephropathy in diabetes mellitus and that with reference to albuminuria.
Materials and Methods: A total of 150 type 2 diabetics in the age group 35 - 50 years were enrolled as three groups, comprising 50 each, based on albuminuria. 50 healthy age and gender matched subjects constituted the control group. Serum NT and Insulin were assessed by ELISA. HbA1c was quantitated by immunoturbidimetric method and microalbumin was assessed by turbilatex method. Routine biochemistry was enabled through ERBA EM-200 fully automated analyzer. Stringent quality control was affected. The study was begun following approval accorded by the competent committees.
Results: NT levels were positively correlated with albumin-creatinine ratio and insulin resistance. NT could be used as a predictor of impending vascular complications in diabetic nephropathy.
Conclusion: NT levels could act as a predictor of oxidative stress mediated diabetic nephropathy in the light of albuminuria.
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15
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Fiserova I, Trinh MD, Elkalaf M, Vacek L, Heide M, Martinkova S, Bechynska K, Kosek V, Hajslova J, Fiser O, Tousek P, Polak J. Isoprenaline modified the lipidomic profile and reduced β-oxidation in HL-1 cardiomyocytes: In vitro model of takotsubo syndrome. Front Cardiovasc Med 2022; 9:917989. [PMID: 36072861 PMCID: PMC9441769 DOI: 10.3389/fcvm.2022.917989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
Recent studies have suggested a pathogenetic link between impaired mitochondria and Takotsubo syndrome (TTS), which is closely connected with catecholamine overstimulation, poor outcomes, and changes in lipid metabolism. We investigated the changes in lipid metabolism at the level of fatty acid β-oxidation and changes in the intracellular lipidomic spectrum. The immortalized cell line of HL-1 cardiomyocytes was used in this study as an established in vitro model of TTS. The cells were exposed to the non-selective β-agonist isoprenaline (ISO) for acute (2 h) and prolonged (24 h) periods. We investigated the impact on mitochondrial adenosine 5’-triphosphate (ATP) production and β-oxidation using real-time cell metabolic analysis, total lipid content, and changes in the lipidomic spectrum using high-performance liquid chromatography (HPLC) and mass spectrometry. Furthermore, modifications of selected lipid transporters were determined using real-time – polymerase chain reaction (RT-PCR) and/or Western blot techniques. By choosing this wide range of targets, we provide a detailed overview of molecular changes in lipid metabolism during catecholamine overstimulation. The present study demonstrates that acute exposure to ISO decreased ATP production by up to 42.2%, and prolonged exposure to ISO decreased β-oxidation by 86.4%. Prolonged exposure to ISO also increased lipid accumulation by 4%. Lipid spectrum analysis of prolonged exposure to ISO showed a reduced concentration of cardioprotective and an increased concentration of lipotoxic lipid molecules during long-term exposure. Decreased lipid utilization can lead to higher intracellular lipid accumulation and the formation of lipotoxic molecules. Changes in the lipid spectrum can induce pathophysiological signaling pathways leading to cardiomyocyte remodeling or apoptosis. Thus, changes in lipid metabolism induced by excessive doses of catecholamines may cause TTS and contribute to a progression of heart failure, which is at increased risk after a TTS episode.
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Affiliation(s)
- Ivana Fiserova
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
- Department of Cardiology, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czechia
| | - Minh Duc Trinh
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
- Department of Cardiology, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czechia
| | - Moustafa Elkalaf
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
- Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czechia
| | - Lukas Vacek
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
| | - Marek Heide
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
| | - Stanislava Martinkova
- Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague, Czechia
| | - Kamila Bechynska
- Department of Food Analysis and Nutrition, University of Chemistry and Technology Prague, Prague, Czechia
| | - Vit Kosek
- Department of Food Analysis and Nutrition, University of Chemistry and Technology Prague, Prague, Czechia
| | - Jana Hajslova
- Department of Food Analysis and Nutrition, University of Chemistry and Technology Prague, Prague, Czechia
| | - Ondrej Fiser
- Department of Biomedical Technology, Faculty of Biomedical Engineering, Czech Technical University in Prague, Prague, Czechia
| | - Petr Tousek
- Department of Cardiology, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czechia
| | - Jan Polak
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czechia
- *Correspondence: Jan Polak,
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Ilderbayev O, Okassova A, Rakhyzhanova S, Ilderbayeva G, Zhazykbayeva L. The levels of oxidative stress in a combination of stress factors. J Med Life 2022; 15:927-931. [PMID: 36188645 PMCID: PMC9514812 DOI: 10.25122/jml-2021-0060] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 02/18/2022] [Indexed: 11/05/2022] Open
Abstract
We studied the effect of the combined action of ionizing radiation and induced immobilization stress on the lipid peroxidation process and antioxidant protection of organs (mesenteric lymph nodes, spleen, adrenal glands, thymus, and liver) and immune cels - the blood lymphocytes. Results were obtained on the role of free-radical oxidation in combination with exposure to ionizing radiation and immobilization stress at an early stage in the experiment. Gamma radiation in the acute period resulted in significant changes in lipoperoxidation and antioxidant systems. The first period of immobilization stress was marked by the imbalance of LPO-AOS systems disturbance with an accumulation of toxic compounds in tissues which had affected their function. The combined sublethal gamma radiation and immobilization stress disturbed the functional activity of adaptive systems of the body in the early stage of adaptation syndrome. Furthermore, the results show the dominant role of ionizing radiation in it.
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Affiliation(s)
- Oralbek Ilderbayev
- Department of General Biology and Genomics, Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, Nur-Sultan, Kazakhstan,Corresponding Author: Oralbek Ilderbayev, Department of General Biology and Genomics, Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, Nur-Sultan, Kazakhstan. E-mail:
| | - Assem Okassova
- Department of General Biology and Genomics, Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, Nur-Sultan, Kazakhstan
| | - Saule Rakhyzhanova
- Department of Physiological Disciplines, Semey Medical University, Semey, Kazakhstan
| | - Gulzhan Ilderbayeva
- Department of Biotechnology and Microbiology, Natural Science Faculty, NCJSC L.N. Gumilyov Eurasian National University, Nur-Sultan, Kazakhstan
| | - Lashyn Zhazykbayeva
- Department of Physiological Disciplines, Semey Medical University, Semey, Kazakhstan
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17
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Palackic A, Jay JW, Duggan RP, Branski LK, Wolf SE, Ansari N, El Ayadi A. Therapeutic Strategies to Reduce Burn Wound Conversion. Medicina (B Aires) 2022; 58:medicina58070922. [PMID: 35888643 PMCID: PMC9315582 DOI: 10.3390/medicina58070922] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/02/2022] [Accepted: 07/08/2022] [Indexed: 11/16/2022] Open
Abstract
Burn wound conversion refers to the phenomenon whereby superficial burns that appear to retain the ability to spontaneously heal, convert later into deeper wounds in need of excision. While no current treatment can definitively stop burn wound conversion, attempts to slow tissue damage remain unsatisfactory, justifying the need for new therapeutic interventions. To attenuate burn wound conversion, various studies have targeted at least one of the molecular mechanisms underlying burn wound conversion, including ischemia, inflammation, apoptosis, autophagy, generation of reactive oxygen species, hypothermia, and wound rehydration. However, therapeutic strategies that can target various mechanisms involved in burn wound conversion are still lacking. This review highlights the pathophysiology of burn wound conversion and focuses on recent studies that have turned to the novel use of biologics such as mesenchymal stem cells, biomaterials, and immune regulators to mitigate wound conversion. Future research should investigate mechanistic pathways, side effects, safety, and efficacy of these different treatments before translation into clinical studies.
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Affiliation(s)
- Alen Palackic
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA; (A.P.); (J.W.J.); (R.P.D.); (L.K.B.); (S.E.W.)
- Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, A-8036 Graz, Austria
| | - Jayson W. Jay
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA; (A.P.); (J.W.J.); (R.P.D.); (L.K.B.); (S.E.W.)
| | - Robert P. Duggan
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA; (A.P.); (J.W.J.); (R.P.D.); (L.K.B.); (S.E.W.)
| | - Ludwik K. Branski
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA; (A.P.); (J.W.J.); (R.P.D.); (L.K.B.); (S.E.W.)
| | - Steven E. Wolf
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA; (A.P.); (J.W.J.); (R.P.D.); (L.K.B.); (S.E.W.)
| | - Naseem Ansari
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA;
| | - Amina El Ayadi
- Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA; (A.P.); (J.W.J.); (R.P.D.); (L.K.B.); (S.E.W.)
- Correspondence:
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Phosphodiesterase (PDE) III inhibitor, Cilostazol, improved memory impairment in aluminum chloride-treated rats: modulation of cAMP/CREB pathway. Inflammopharmacology 2022; 30:2477-2488. [PMID: 35727381 DOI: 10.1007/s10787-022-01010-1] [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: 05/10/2022] [Accepted: 05/12/2022] [Indexed: 11/05/2022]
Abstract
The most prevalent type of dementia is Alzheimer's disease (AD), which is currently incurable. Existing treatments for Alzheimer's disease, such as acetylcholinesterase inhibitors, are only effective for symptom relief. Disease-modifying medications for Alzheimer's disease are desperately required, given the enormous burdens that the disease places on individuals and communities. Phosphodiesterase (PDE) inhibitors are gaining a lot of attention in the research community because of their potential in treating age-related cognitive decline. Cilostazol is a selective PDE III inhibitor used as antiplatelet agent through cAMP response element-binding (CREB) protein phosphorylation pathway (cAMP/CREB). The neuroprotective effect of cilostazol in AD-like cognitive decline in rats was investigated in this study. After 2 months of intraperitoneal administration of 10 mg/kg aluminum chloride, Morris water maze and Y-maze (behavioral tests) were performed. After that, histological and biochemical examinations of the hippocampal region were carried out. Aluminum chloride-treated rats showed histological, biochemical, and behavioral changes similar to Alzheimer's disease. Cilostazol improved rats' behavioral and histological conditions, raised neprilysin level while reduced levels of amyloid-beta protein and phosphorylated tau protein. It also decreased the hippocampal levels of tumor necrosis factor-alpha, nuclear factor-kappa B, FAS ligand, acetylcholinesterase content, and malondialdehyde. These outcomes demonstrate the protective activity of cilostazol versus aluminum-induced memory impairment.
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Reprint of: Oxygen Free Radicals and Iron in Relation to Biology and Medicine: Some Problems and Concepts. Arch Biochem Biophys 2022; 726:109246. [PMID: 35680438 DOI: 10.1016/j.abb.2022.109246] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Nephroprotective effects of 4-4(hydroxyl-3 methoxyphenyl)-2-butane against sodium tellurite induced acute kidney dysfunction by attenuating oxidative stress and inflammatory cytokines in rats. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2022.103857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Wu J, Gao T, Zhao L, Bao H, Yu C, Hu J, Ma F. Investigating Phragmites australis response to copper exposure using physiologic, Fourier Transform Infrared and metabolomic approaches. FUNCTIONAL PLANT BIOLOGY : FPB 2022; 49:365-381. [PMID: 35290177 DOI: 10.1071/fp21258] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 01/19/2022] [Indexed: 06/14/2023]
Abstract
Phragmites australis (Cav.) Trin. ex Steud is a landscape plant with resistance to heavy metals that has significance in phytoremediation. However, little is known about the metabolomic background of the heavy metal resistance mechanisms of Phragmites . We studied copper stress on Phragmites and monitored physiological indicators such as malondialdehyde (MDA) and electrolyte leakage (EL). In addition, Fourier Transform Infrared (FTIR) was used to study the related chemical composition in the roots, stems, and leaves under copper stress. Furthermore, LC-MS technology was used to analyse the plants metabolic profile. Results showed that increased copper concentration in Phragmites led to the accumulation of MDA and EL. FTIR spectrum detected the presence of O-H and C=O stretching. O-H stretching was related to the presence of flavonoids, while C=O stretching reflected the presence of protein amide I. The latter was related to the change of amino acid composition. Both flavonoids and amino acids are regarded as contributors to the antioxidant of Phragmites under copper stress. Metabolomics analysis revealed that arginine and ayarin were accumulated and Phragmites leaves responded to copper stress with changes in the pool size of arginine and ayarin. It is speculated that they could improve resistance. Arginine is accumulated through two pathways: the citrulline decomposition and conversion pathway; and the circular pathway composed of ornithine, citrulline, l -argininosuccinate and arginine. Ayarin is synthesised through the quercetin methylation pathway. This study elucidates the antioxidant mechanisms for enhancing its resistance to heavy metal stress, thus improving of phytoremediation efficiency.
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Affiliation(s)
- Jieting Wu
- School of Environmental Science, Liaoning University, Shenyang 110036, People's Republic of China
| | - Tian Gao
- School of Environmental Science, Liaoning University, Shenyang 110036, People's Republic of China
| | - Lei Zhao
- State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, People's Republic of China
| | - Hongxu Bao
- School of Environmental Science, Liaoning University, Shenyang 110036, People's Republic of China
| | - Chang Yu
- School of Environmental Science, Liaoning University, Shenyang 110036, People's Republic of China
| | - Jianing Hu
- Dalian Neusoft University of Information, Dalian 116032, People's Republic of China
| | - Fang Ma
- State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, People's Republic of China
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22
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Kant V, Sharma M, Jangir BL, Kumar V. Acceleration of wound healing by quercetin in diabetic rats requires mitigation of oxidative stress and stimulation of the proliferative phase. Biotech Histochem 2022; 97:461-472. [PMID: 35105256 DOI: 10.1080/10520295.2022.2032829] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Increased oxidative stress in diabetic wound areas impairs wound healing. Quercetin exhibits significant antioxidant properties. We investigated the effects of topical quercetin on antioxidant status in diabetic wound areas and its effect on wound healing in rats. A 2 cm2 cutaneous wound was produced on the back of streptozotocin induced diabetic and normal rats. Rats were divided into three groups of 20: normal healthy control group, diabetic group and quercetin treated diabetic group. The control and diabetic groups were treated topically with ointment base once daily for 21 days. The quercetin treated diabetic rats were treated similarly with ointment containing quercetin. The quercetin treated diabetic group exhibited increased levels of catalase, glutathione peroxidase, superoxide dismutase and total thiols compared to the diabetic group. Nitrite levels in the diabetic group were decreased significantly on day 3 compared to the healthy control group. Malondialdehyde levels were decreased in the quercetin treated diabetic group compared to the diabetic group. The expression of proliferating cell nuclear antigen) (PCNA) was greater in the quercetin treated diabetic group on day 7 compared to healthy control and diabetic groups. Formation of granulation tissue and the quality of healed tissue was improved in the quercetin treated diabetic group compared to the diabetic group. Quercetin improves antioxidant status in wounds of diabetic rats and stimulates the proliferation phase, which accelerates wound healing.
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Affiliation(s)
- Vinay Kant
- Department of Veterinary Pharmacology and Toxicology, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, India
| | - Maneesh Sharma
- Department of Veterinary Clinical Complex, College of Veterinary Sciences, Lala Lajpat Rai University of Veterinary and Animal Science, Hisar, India
| | - Babu Lal Jangir
- Department of Veterinary Pathology, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, India
| | - Vinod Kumar
- Department of Veterinary Pharmacology and Toxicology, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, India
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23
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Rodríguez ML, Millán I, Ortega ÁL. Cellular targets in diabetic retinopathy therapy. World J Diabetes 2021; 12:1442-1462. [PMID: 34630899 PMCID: PMC8472497 DOI: 10.4239/wjd.v12.i9.1442] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/08/2021] [Accepted: 08/03/2021] [Indexed: 02/06/2023] Open
Abstract
Despite the existence of treatment for diabetes, inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy. Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles. Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease. Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia. The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy. Therefore, in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that, potentially, can prevent the development and progression of the disease.
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Affiliation(s)
- María Lucía Rodríguez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot 46100, Valencia, Spain
| | - Iván Millán
- Neonatal Research Group, Health Research Institute La Fe, Valencia 46026, Valencia, Spain
| | - Ángel Luis Ortega
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot 46100, Valencia, Spain
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24
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Beldi VF, Rosique MJ, Tirapelli LF, Moriguti EK, Nunes AA, Farina JA, Evora PRB. Intradermal methylene blue administration on the progression of burn injuries. J Wound Care 2021; 30:VIIIi-VIIIx. [PMID: 34570634 DOI: 10.12968/jowc.2021.30.sup9a.viii] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE A burn injury has two defined areas: central necrosis and an adjacent area of ischaemia, which may or may not progress to necrosis. The concentration of nitric oxide (NO) increases after burn injury and may originate from potent oxidising agents. Methylene blue (MB) may act as an antioxidant and is supposed to reduce burn progression. This investigation was carried out to evaluate the effects of intradermal MB on necrosis progression in burns. METHODS Full-thickness burn injuries were performed by applying a heated metal comb on the shaved back of male Wistar rats. The animals were divided into three groups: Control (C, n=7); MB (2mg/kg) one hour after burn injury (MB1h, n=11); and MB (2mg/kg) six hours after burn injury (MB6h, n=8). After seven days the lesions were photographed for visual assessment of burn necrosis; full-thickness cuts of lesions were dyed with Masson and Giemsa for microscopic histopathology; and tissue fragments of unburned interspaces were processed for chemiluminescence with nitrite/nitrate (NOX) and malondialdehyde (MDA) as oxidative stress markers. RESULTS No statistically significant differences between groups were observed during visual analysis and NOX dosage. However, in microscopic analysis, the MB1h and MB6h groups showed smaller areas of necrosis, less inflammatory infiltration, and a more significant extension of interspaces. Furthermore, the dosage of MDA revealed that the MB1h group showed lower values when compared with the control group (p=0.001). CONCLUSIONS The study provided good evidence that MB intradermal injection can reduce necrosis progression in ischaemic perilesional areas and suggests an alternative to treating burns.
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Affiliation(s)
- Vinícius Fm Beldi
- Department of Surgery, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Marina J Rosique
- Department of Surgery, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Luis Fernando Tirapelli
- Department of Surgery, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Eny Ku Moriguti
- Department of Surgery, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Altacílio A Nunes
- Department of Social Medicine, Ribeirão Preto School of Medicine, University of São Paulo, Brazil
| | - Jayme A Farina
- Department of Surgery, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Paulo Roberto B Evora
- Department of Surgery, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
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25
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Short Overview of Some Assays for the Measurement of Antioxidant Activity of Natural Products and Their Relevance in Dermatology. Molecules 2021; 26:molecules26175301. [PMID: 34500732 PMCID: PMC8433703 DOI: 10.3390/molecules26175301] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/25/2021] [Accepted: 08/25/2021] [Indexed: 12/19/2022] Open
Abstract
Impaired systemic redox homeostasis is implicated in the onset and development of various diseases, including skin diseases. Therefore, continuous search for natural products with antioxidant bioactivities applicable in biomedicine is attractive topic of general interest. Research efforts aiming to validate antioxidant potentials of natural products has led to the development of several assays based on various test principles. Hence, understanding the advantages and limitations of various assays is important for selection of assays useful to study antioxidant and related bioactivities of natural products of biomedical interest. This review paper gives a short overview on some chemical and cellular bioassays used to estimate the antioxidant activity of chosen natural products together with a brief overview on the use of natural products with antioxidant activities as adjuvant medicinal remedies in dermatology.
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26
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Sunar M, Yazici GN, Mammadov R, Kurt N, Arslan YK, Süleyman H. Coenzyme Q10 effect on cisplatin-induced oxidative retinal injury in rats. Cutan Ocul Toxicol 2021; 40:312-318. [PMID: 34325578 DOI: 10.1080/15569527.2021.1949336] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
AIM In this study, it was aimed to investigate the effect of coenzyme Q10 (CoQ10) on cisplatin-induced oxidative retinal damage in rats biochemically and histopathologically. MATERIALS AND METHODS Thirty male Wistar albino rats were divided into 3 groups randomly: untreated control (C group), only 2.5 mg/kg cisplatin daily administrated group for 2 weeks (CP group), 2.5 mg/kg cisplatin + 20 mg/kg orally CoQ10 daily administrated group for 2 weeks (CoQC group). At the end of experimental period, blood samples obtained before sacrification for the biochemical examination of serum malondialdehyde (MDA), total glutathione (tGSH), total oxidant system (TOS), total antioxidant systemic (TAS) levels and after eyes were removed for examined histopathology. RESULTS As a result of our study, severe histopathological damage was detected in the retinal tissue of the cisplatin group with serum malondialdehyde (MDA) and total oxidant system (TOS) levels were high and total glutathione (tGSH) and total antioxidant systemic (TAS) levels were low. However, it was observed that the histopathological damage associated with cisplatin was decreased in the retinal tissue of the CoQ10 group, which inhibited the increase in blood serum MDA/TOS levels and decrease in tGSH/TAS levels. CONCLUSION The biochemical and histopathological results of our study were compatible with each other, so we concluded that the damage to the rat retinal tissue caused by cisplatin may be reversible with coenzyme.
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Affiliation(s)
- Mukadder Sunar
- Department of Anatomy, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Gulce Naz Yazici
- Department of Histology and Embryology, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Renad Mammadov
- Department of Pharmacology, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Nezahat Kurt
- Department of Biochemistry, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Yusuf Kemal Arslan
- Department of Biostatistics, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
| | - Halis Süleyman
- Department of Pharmacology, School of Medicine, Erzincan Binali Yıldırım University, Erzincan, Turkey
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27
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Hung SW, Zhang R, Tan Z, Chung JPW, Zhang T, Wang CC. Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review. Med Res Rev 2021; 41:2489-2564. [PMID: 33948974 PMCID: PMC8252000 DOI: 10.1002/med.21802] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 12/23/2020] [Accepted: 03/19/2021] [Indexed: 12/13/2022]
Abstract
Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via multiple pathways, including MAPK/MEK/ERK, PI3K/Akt/mTOR, NF-κB, Rho/ROCK, reactive oxidative stress, tumor necrosis factor, transforming growth factor-β, Wnt/β-catenin, vascular endothelial growth factor, estrogen, and cytokines. The underlying pathophysiological mechanisms include proliferation, apoptosis, autophagy, migration, invasion, fibrosis, angiogenesis, oxidative stress, inflammation, and immune escape. Current medical treatments for EM are mainly hormonal and symptomatic, and thus the development of new, effective, and safe pharmaceuticals targeting specific molecular and signaling pathways is needed. Here, we systematically reviewed the literature focused on pharmaceuticals that specifically target the molecular and signaling pathways involved in the pathophysiology of EM. Potential drug targets, their upstream and downstream molecules with key aberrant signaling, and the regulatory mechanisms promoting the growth and development of endometriotic cells and tissues were discussed. Hormonal pharmaceuticals, including melatonin, exerts proapoptotic via regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib exerts antiproliferative effect via MAPK/ERK pathway and antiangiogenesis activity via VEGF/VEGFR pathway. N-acetyl cysteine, curcumin, and ginsenoside exert antioxidant and anti-inflammatory effects via radical scavenging activity. Natural products have high efficacy with minimal side effects; for example, resveratrol and epigallocatechin gallate have multiple targets and provide synergistic efficacy to resolve the complexity of the pathophysiology of EM, showing promising efficacy in treating EM. Although new medical treatments are currently being developed, more detailed pharmacological studies and large sample size clinical trials are needed to confirm the efficacy and safety of these treatments in the near future.
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Affiliation(s)
- Sze Wan Hung
- Department of Obstetrics and GynaecologyThe Chinese University of Hong KongHong Kong
| | - Ruizhe Zhang
- Department of Obstetrics and GynaecologyThe Chinese University of Hong KongHong Kong
- Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou
| | - Zhouyurong Tan
- Department of Obstetrics and GynaecologyThe Chinese University of Hong KongHong Kong
| | | | - Tao Zhang
- Department of Obstetrics and GynaecologyThe Chinese University of Hong KongHong Kong
| | - Chi Chiu Wang
- Department of Obstetrics and GynaecologyThe Chinese University of Hong KongHong Kong
- Reproduction and Development, Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong
- School of Biomedical SciencesThe Chinese University of Hong KongHong Kong
- Chinese University of Hong Kong‐Sichuan University Joint Laboratory in Reproductive MedicineThe Chinese University of Hong KongHong Kong
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28
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Yamaguchi Y, Hirata Y, Saito T, Kumagai H. Combined Effects of Amino Acids in Garlic and Buna-Shimeji ( Hypsizygus marmoreus) on Suppression of CCl 4-Induced Hepatic Injury in Rats. Foods 2021; 10:foods10071491. [PMID: 34199038 PMCID: PMC8306630 DOI: 10.3390/foods10071491] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/15/2021] [Accepted: 06/22/2021] [Indexed: 12/31/2022] Open
Abstract
The combination of the garlic-derived amino acid, S-allyl-l-cysteine sulfoxide (ACSO), and ornithine or arginine on CCl4-induced hepatic injury was examined. After investigating the effectiveness of the mixture of ACSO and ornithine or arginine in preventing hepatic injury in vivo, an extract rich in ACSO and ornithine was prepared by converting arginine in garlic to ornithine by arginase from Hypsizygus marmoreus (buna-shimeji), after screening the productivity of ornithine among 12 kinds of mushrooms. Co-administration of ACSO with ornithine or arginine suppressed the increase in aspartate transaminase, alanine transaminase, and thiobarbituric acid reactive substance, and the decrease in glutathione S-transferase and cytochrome p450 2E1 activities after CCl4 injection more effectively than a single administration of ACSO. All extracts prepared from garlic and buna-shimeji with low and high contents of ACSO and arginine or ornithine significantly suppressed CCl4-induced hepatic injury in rats. Considering that ACSO is tasteless, odourless, and enhances taste, and ornithine has a flat or sweet taste and masks bitterness, the extract rich in ACSO and ornithine from garlic and buna-shimeji could be considered a potential antioxidant food material that can be added to many kinds of food to prevent hepatic injury.
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Affiliation(s)
- Yusuke Yamaguchi
- Department of Chemistry and Life Science, Nihon University, 1866 Kameino, Fujisawa-shi 252-0880, Japan; (Y.Y.); (Y.H.)
| | - Yushi Hirata
- Department of Chemistry and Life Science, Nihon University, 1866 Kameino, Fujisawa-shi 252-0880, Japan; (Y.Y.); (Y.H.)
| | - Takeshi Saito
- ACERA Co., Ltd., 156 Nishitakahashi-machi, Kofu-shi 400-0826, Japan;
| | - Hitomi Kumagai
- Department of Chemistry and Life Science, Nihon University, 1866 Kameino, Fujisawa-shi 252-0880, Japan; (Y.Y.); (Y.H.)
- Correspondence: ; Tel.: +81-466-3946
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29
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Bedir F, Kocaturk H, Turangezli O, Sener E, Akyuz S, Ozgeris FB, Dabanlioglu B, Suleyman H, Altuner D, Suleyman B. The protective effect of lycopene against oxidative kidney damage associated with combined use of isoniazid and rifampicin in rats. ACTA ACUST UNITED AC 2021; 54:e10660. [PMID: 34037090 PMCID: PMC8148980 DOI: 10.1590/1414-431x2020e10660] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 02/09/2021] [Indexed: 12/13/2022]
Abstract
It is known that the combined use of antibiotics, such as isoniazid and rifampicin, in the treatment of tuberculosis causes oxidative kidney damage. The aim of this study was to biochemically and histopathologically investigate the effect of lycopene on oxidative kidney damage due to the administration of isoniazid and rifampicin in albino Wistar male rats. Lycopene at a dose of 5 mg/kg was orally administered to lycopene+isoniazid+rifampicin (LIR) rats, and normal sunflower oil (0.5 mL) was orally administered to isoniazid+rifampicin (IR) and healthy control (HG) rats as vehicle by gavage. One hour after the administration of lycopene and vehicle, 50 mg/kg isoniazid and rifampicin were given orally to the LIR and IR groups. This procedure was performed once a day for 28 days. Rats were sacrificed by a high dose of anesthesia at the end of this period, and oxidant-antioxidant parameters were measured in the removed kidney tissues. Creatinine and blood urea nitrogen (BUN) levels were measured in blood samples, and kidney tissues were also evaluated histopathologically. The combined administration of isoniazid and rifampicin changed the oxidant-antioxidant balance in favor of oxidants, and it increased blood urea nitrogen and creatinine levels, which are indicators of kidney function. Co-administration of isoniazid and rifampicin also caused oxidative kidney damage. Lycopene biochemically and histopathologically decreased oxidative kidney damage induced by isoniazid and rifampicin administration. These results suggested that lycopene may be beneficial in the treatment of nephrotoxicity due to isoniazid and rifampicin administration.
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Affiliation(s)
- F Bedir
- Department of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, Erzurum, Turkey
| | - H Kocaturk
- Department of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, Erzurum, Turkey
| | - O Turangezli
- Department of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, Erzurum, Turkey
| | - E Sener
- Department of Pathology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - S Akyuz
- Department of Microbiology, Mengucek Gazi Training and Research Hospital, Erzincan, Turkey
| | - F B Ozgeris
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Ataturk University, Erzurum, Turkey
| | - B Dabanlioglu
- Department of Microbiology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey
| | - H Suleyman
- Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey
| | - D Altuner
- Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey
| | - B Suleyman
- Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey
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30
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Jouini N, Saied Z, Ben Sassi S, Nebli F, Messaoud T, Hentati F, Belal S. Impacts of Iron Metabolism Dysregulation on Alzheimer's Disease. J Alzheimers Dis 2021; 80:1439-1450. [PMID: 33682709 DOI: 10.3233/jad-201250] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND Iron plays an important role in maintaining cell survival, with normal iron trafficking known to be regulated by the ceruloplasmin-transferrin (Cp-Tf) antioxidant system. Disruption to this system is thought to be detrimental to normal brain function. OBJECTIVE To determine whether an imbalance of iron and the proteins involved in its metabolism (ceruloplasmin and transferrin) are linked to Alzheimer's disease (AD) and to the expression of amyloid-beta (Aβ) peptide 1-42 (Aβ1-42), which is a major species of Aβ, and the most toxic. METHODS We evaluated the concentrations of iron, calcium, magnesium, and Aβ1-42 in the cerebrospinal fluid (CSF) of patients with AD and cognitively normal controls. Correlations between the components of the Cp-Tf antioxidant system in plasma were studied to determine the role of peripheral blood in the onset and/or development of AD. We used commercial ELISA immunoassays to measure Aβ1-42, immunoturbidimetry to quantify ceruloplasmin and transferrin, and colorimetry to quantify iron, calcium, and magnesium. RESULTS We found that the AD group had lower CSF concentrations of Aβ1-42 (p < 0.001) and calcium (p < 0.001), but a higher CSF concentration of iron (p < 0.001). Significantly lower plasma concentrations of ceruloplasmin (p = 0.003), transferrin (mean, p < 0.001), and iron (p < 0.001) were observed in the AD group than in cognitively normal adults. Moreover, we found a strong interdependence between most of these components. CONCLUSION Iron dyshomeostasis has a crucial role in the onset of AD and/or its development. Correcting metal misdistribution is an appealing therapeutic strategy for AD.
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Affiliation(s)
- Najla Jouini
- Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Faculty of Medicine of Tunis, Neurosciences Department, University of Tunis El Manar, Tunis, Tunisia.,Biology Laboratory, Children's Hospital, Tunis, Tunisia.,Neurology Department, National Institute of Neurology, Tunis, Tunisia.,Current address: Institute of Technology, Tralee, Co. Kerry, Ireland
| | - Zakaria Saied
- Faculty of Medicine of Tunis, Neurosciences Department, University of Tunis El Manar, Tunis, Tunisia.,Neurology Department, National Institute of Neurology, Tunis, Tunisia
| | - Samia Ben Sassi
- Faculty of Medicine of Tunis, Neurosciences Department, University of Tunis El Manar, Tunis, Tunisia.,Neurology Department, National Institute of Neurology, Tunis, Tunisia
| | - Fatma Nebli
- Faculty of Medicine of Tunis, Neurosciences Department, University of Tunis El Manar, Tunis, Tunisia.,Neurology Department, National Institute of Neurology, Tunis, Tunisia
| | | | - Faycel Hentati
- Faculty of Medicine of Tunis, Neurosciences Department, University of Tunis El Manar, Tunis, Tunisia.,Neurology Department, National Institute of Neurology, Tunis, Tunisia
| | - Samir Belal
- Faculty of Medicine of Tunis, Neurosciences Department, University of Tunis El Manar, Tunis, Tunisia.,Neurology Department, National Institute of Neurology, Tunis, Tunisia
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31
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Tokoro M, Gotoh K, Kudo Y, Hirashita Y, Iwao M, Arakawa M, Endo M, Oribe J, Masaki T, Honda K, Kakuma T, Seike M, Murakami K, Shibata H. α-Tocopherol suppresses hepatic steatosis by increasing CPT-1 expression in a mouse model of diet-induced nonalcoholic fatty liver disease. Obes Sci Pract 2021; 7:91-99. [PMID: 33680496 PMCID: PMC7909598 DOI: 10.1002/osp4.460] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 09/29/2020] [Accepted: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Aim Antioxidant therapy for with vitamin E appears to be effective for the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism of action and optimal therapeutic dosage is unclear. The present study was undertaken to examine whether the effects of α‐tocopherol (α‐Toc) on NAFLD are dose‐dependent in a diet‐induced obese model. Methods Male mice were fed standard chow, high‐fat (HF) diet, HF diet with low‐dose, or with high dose of α‐Toc supplementation. Histological findings, triglyceride content, and the levels of protein expression related to fatty acid synthesis/oxidation such as carnitine palmitoyltransferase I (CPT‐1) of liver were evaluated. In addition, 2‐tetradecylglycidic acid (TDGA), a CPT‐1 inhibitor, was administered to mice fed HF diet with low‐dose of α‐Toc. Finally, HepG2 cells in fat‐loaded environment were treated with 0–50 μM α‐Toc. Results Treatment of low‐dose of α‐Toc decreased HF‐induced hepatic fat accumulation, but this finding was not observed in treatment of high dose of α‐Toc. HF‐induced reduction of CPT‐1 was attenuated with low‐dose of α‐Toc but not with high dose of α‐Toc. TDGA suppressed the improvement of histological findings in liver induced by low‐dose of α‐Toc treatment. CPT‐1 expression in HepG2 cells increased in response to low‐dose of α‐Toc, but not in high dose. Conclusions Dual action of α‐Toc on CPT‐1 protein levels was observed. The effect of vitamin E on NAFLD may be not be dose‐dependent.
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Affiliation(s)
- Masanori Tokoro
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan.,Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Koro Gotoh
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
| | - Yoko Kudo
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Yuka Hirashita
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Masao Iwao
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Mie Arakawa
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Mizuki Endo
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Junya Oribe
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Takayuki Masaki
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
| | - Koichi Honda
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Tetsuya Kakuma
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
| | - Masataka Seike
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Kazunari Murakami
- Department of Gastroenterology Faculty of Medicine Oita University Oita Japan
| | - Hirotaka Shibata
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology Faculty of Medicine Oita University Oita Japan
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Prayitno A, Oetari RA, Shahiddin I, Elmanda AY, Septiarini AD, Hasriyani H, Dharmayanti L, Saristiana Y, Sari YDP. α-Mangosteen from Garcinia Mangostana Linn and its Effect in Blood Insulin and Sugar Levels in Hyperglycemic Rat. JOURNAL OF CLINICAL AND EXPERIMENTAL INVESTIGATIONS 2021. [DOI: 10.29333/jcei/9767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Ensminger DC, Salvador-Pascual A, Arango BG, Allen KN, Vázquez-Medina JP. Fasting ameliorates oxidative stress: A review of physiological strategies across life history events in wild vertebrates. Comp Biochem Physiol A Mol Integr Physiol 2021; 256:110929. [PMID: 33647461 DOI: 10.1016/j.cbpa.2021.110929] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 02/17/2021] [Accepted: 02/21/2021] [Indexed: 02/06/2023]
Abstract
Fasting is a component of many species' life history due to environmental factors or behavioral patterns that limit access to food. Despite metabolic and physiological challenges associated with these life history stages, fasting-adapted wild vertebrates exhibit few if any signs of oxidative stress, suggesting that fasting promotes redox homeostasis. Here we review mammalian, avian, reptilian, amphibian, and piscine examples of animals undergoing fasting during prolonged metabolic suppression (e.g. hibernation and estivation) or energetically demanding processes (e.g. migration and breeding) to better understand the mechanisms underlying fasting tolerance in wild vertebrates. These studies largely show beneficial effects of fasting on redox balance via limited oxidative damage. Though some species exhibit signs of oxidative stress due to energetically or metabolically extreme processes, fasting wild vertebrates largely buffer themselves from the negative consequences of oxidative damage through specific strategies such as elevating antioxidants, selectively maintaining redox balance in critical tissues, or modifying behavioral patterns. We conclude with suggestions for future research to better elucidate the protective effects of fasting on oxidative stress as well as disentangle the impacts from other life history stages. Further research in these areas will facilitate our understanding of the mechanisms wild vertebrates use to mitigate the negative impacts associated with metabolically-extreme life history stages as well as potential translation into therapeutic interventions in non-fasting-adapted species including humans.
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Affiliation(s)
- David C Ensminger
- Department of Integrative Biology, University of California, Berkeley, USA
| | | | - B Gabriela Arango
- Department of Integrative Biology, University of California, Berkeley, USA
| | - Kaitlin N Allen
- Department of Integrative Biology, University of California, Berkeley, USA
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Bonomo R, Cavaletti G. Clinical and biochemical markers in CIPN: A reappraisal. Rev Neurol (Paris) 2021; 177:890-907. [PMID: 33648782 DOI: 10.1016/j.neurol.2020.11.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 09/11/2020] [Accepted: 11/03/2020] [Indexed: 12/14/2022]
Abstract
The increased survival of cancer patients has raised growing public health concern on associated long-term consequences of antineoplastic treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is a primarily sensory polyneuropathy, which may be accompanied by pain, autonomic disturbances, and motor deficit. About 70% of treated cancer patients might develop CIPN during or after the completion of chemotherapy, and in most of them such complication persists after six months from the treatment. The definition of the potential risk of development and resolution of CIPN according to a clinical and biochemical profile would be certainly fundamental to tailor chemotherapy regimen and dosage on individual susceptibility. In recent years, patient-reported and clinician-related tools along with quality of life instruments have been featured as primary outcomes in clinical setting and randomized trials. New studies on metabolomics markers are further pursuing accurate and easily accessible indicators of peripheral nerve damage. The aim of this review is to outline the strengths and pitfalls of current knowledge on CIPN, and to provide a framework for future potential developments of standardized protocols involving clinical and biochemical markers for CIPN assessment and monitoring.
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Affiliation(s)
- R Bonomo
- Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - G Cavaletti
- Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
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Bedir F, Kocaturk H, Ozgeris FB, Yazici GN, Suleyman Z, Suleyman H. The effect of taxifolin on experimental testicular ischaemia reperfusion injury in rats. A biochemical and histopathological analysis. Rev Int Androl 2021; 20:17-23. [PMID: 33531214 DOI: 10.1016/j.androl.2020.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 05/10/2020] [Accepted: 05/26/2020] [Indexed: 11/25/2022]
Abstract
OBJECTIVES The aim of the study is to investigate the protective effect of taxifolin (3,5,7,3,4-pentahydroxy flavanone), a strong antioxidant, against testicular I/R injury in rats biochemically and histopathologically. MATERIALS AND METHODS 50mg/kg taxifolin was administered to taxifolin+testicular torsion-detorsion (TTTD, n-10) group of Albino Wistar male rats by oral gavage. Distilled water .5ml as a solvent was administered to testicular torsion-detorsion (TTD, n-10) and Healthy Control (SG, n-10) groups using the same method. An hour after the administration of taxifolin and distilled water, anaesthesia (ketamine 60mg/kg) was administered to all animal groups. TTD and TTTD group animals were subjected to testicular torsion at 720 degrees for four hours during anaesthesia. At the end of this period, testicular detorsion was applied and perfusion was allowed for four hours. Sham operation was applied to SG group. RESULTS Our biochemical experiment results showed that the amount of malondialdehyde (MDA) in testicular tissue of TTD group presented a significant increase compared to SG and TTTD groups whereas total glutathione (tGSH) and superoxide dismutase (SOD) levels decreased. In addition, while TTD group presented severe histopathological damage in germinal epithelium cell and seminiferous tubule, mild damage was observed in TTTD group. CONCLUSIONS The results of our experiment indicate that taxifolin could be useful in the treatment of testicular I/R damage.
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Affiliation(s)
- Fevzi Bedir
- Department of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, 25040 Erzurum, Turkey
| | - Huseyin Kocaturk
- Department of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, 25040 Erzurum, Turkey
| | - Fatma Betul Ozgeris
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Atatürk University, 25240 Erzurum, Turkey
| | - Gulce Naz Yazici
- Department of Histology and Embryology, Faculty of Medicine, Erzincan Binali Yildirim University, 24100 Erzincan, Turkey
| | - Zeynep Suleyman
- Department of Nursing, Faculty of Health Sciences, Erzincan Binali Yildirim University, 24100 Erzincan, Turkey
| | - Halis Suleyman
- Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, 24100 Erzincan, Turkey.
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36
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Wang H, Li Y, Liu J, Di D, Liu Y, Wei J. Hepatoprotective effect of crude polysaccharide isolated from Lycium barbarum L. against alcohol-induced oxidative damage involves Nrf2 signaling. Food Sci Nutr 2020; 8:6528-6538. [PMID: 33312537 PMCID: PMC7723211 DOI: 10.1002/fsn3.1942] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 09/24/2020] [Accepted: 09/25/2020] [Indexed: 12/21/2022] Open
Abstract
In the present work, we investigated the effect of Lycium barbarum L. polysaccharides (LBPs) on L-02 cells exposed to alcohol exploring the potential molecular mechanisms. Our results suggested that LBPs significantly prevented alcohol-induced hepatotoxicity with dose-dependent effect, indicated by both cell viability and diagnostic indicators of liver damage. Moreover, alcohol induced excessive oxidative stress, as evidenced by an increase of the malondialdehyde level and reactive oxygen species production, while reducing antioxidant enzymes (T-SOD, CAT, and GPx) in liver, were inhibited by administration of LBPs. Furthermore, LBPs reversed the cell apoptosis and increased the mitochondrial membrane potential in alcohol-treated liver cell. Studies of underlying mechanisms revealed that LBPs increased expression levels of Nrf2 expression, which in turn blocked proapoptotic signaling events, restoring the balance between proapoptotic Bax and antiapoptotic Bcl-2 proteins, suppressing activities of cytochrome C (Cyto c), caspase-3, and caspase-9 in L-02 cells stimulation by ethanol. In general, the results showed that the inhibition of alcohol-caused liver damage by LBPs is due at least in part to its antioxidant and antiapoptosis activity via Nrf2 signaling pathway.
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Affiliation(s)
- Han Wang
- Key Laboratory of Chemistry of Northwestern Plant ResourcesLanzhou Institute of Chemical PhysicsChinese Academy of Sciences (CAS)LanzhouChina
- Center of Resource Chemical and New MaterialQingdaoChina
| | - Yongsheng Li
- Key Laboratory of Chemistry of Northwestern Plant ResourcesLanzhou Institute of Chemical PhysicsChinese Academy of Sciences (CAS)LanzhouChina
- School of Public HealthLanzhou UniversityLanzhouChina
| | - Jianfei Liu
- Key Laboratory of Chemistry of Northwestern Plant ResourcesLanzhou Institute of Chemical PhysicsChinese Academy of Sciences (CAS)LanzhouChina
- University of Chinese Academy of SciencesLanzhouChina
| | - Duolong Di
- Key Laboratory of Chemistry of Northwestern Plant ResourcesLanzhou Institute of Chemical PhysicsChinese Academy of Sciences (CAS)LanzhouChina
- Center of Resource Chemical and New MaterialQingdaoChina
| | - Yewei Liu
- School of Public HealthLanzhou UniversityLanzhouChina
| | - Jianteng Wei
- Key Laboratory of Chemistry of Northwestern Plant ResourcesLanzhou Institute of Chemical PhysicsChinese Academy of Sciences (CAS)LanzhouChina
- Center of Resource Chemical and New MaterialQingdaoChina
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Talukdar R. Tracking down the brominated single electron oxidants in recent organic red-ox transformations: photolysis and photocatalysis. Org Biomol Chem 2020; 18:8294-8345. [PMID: 33020775 DOI: 10.1039/d0ob01652g] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
A wide range of organic and inorganic brominated compounds including molecular bromine have been extensively used as oxidants in many organic photo-redox transformations in recent years, an area of ever growing interest because of greener and milder approaches. The oxidation power of these compounds is utilized through both mechanistic pathways (by hydrogen atom transfer or HAT in the absence of a photocatalyst and a combination of single electron transfer or SET and/or HAT in the presence of a photocatalyst). Not only as terminal oxidants for regeneration of photocatalysts, but brominated reactants have also contributed to the oxidation of the reaction intermediate(s) to carry on the radical chain process in several reactions. Here in this review mainly the non-brominative oxidative product formations are discussed, carried out since the last two decades, skipping the instances where they acted as terminal oxidants only to regenerate photocatalysts. The reactions are used to generate natural products, pharmaceuticals and beyond.
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Affiliation(s)
- Ranadeep Talukdar
- Molecular Synthesis and Drug Discovery Laboratory, Centre of Biomedical Research, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-226014, India.
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38
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The Antioxidant Capacity In Vitro and In Vivo of Polysaccharides From Bergenia emeiensis. Int J Mol Sci 2020; 21:ijms21207456. [PMID: 33050354 PMCID: PMC7589108 DOI: 10.3390/ijms21207456] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 10/07/2020] [Accepted: 10/07/2020] [Indexed: 11/17/2022] Open
Abstract
Polysaccharides from Bergenia emeiensis (PBE) showed a robust antioxidant ability on scavenging free radicals in vitro. However, the further antioxidant potential in cell level and in vivo was still unknown. Therefore, in this present study, the protective effect of PBE on human cervical carcinoma cell (Hela) cells and Caenorhabditis elegans against oxidative stress was evaluated. The results showed PBE could reduce the reactive oxygen species (ROS) level in Hela cells and promote the mitochondrial membrane potential. Then, the cell apoptosis was reduced. Moreover, PBE could enhance the survival of C. elegans under thermal stress to 13.44%, and significantly reduce the ROS level, which was connected with the overexpression of sod-3 and the increased nuclear localization of daf-16 transcription factor. Therefore, PBE exhibited a strong antioxidant capacity in the cellular level and for a whole organism. Thus, polysaccharides from B. emeiensis have natural potential to be a safe antioxidant.
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Jawaid P, Rehman MU, Zhao QL, Misawa M, Ishikawa K, Hori M, Shimizu T, Saitoh JI, Noguchi K, Kondo T. Small size gold nanoparticles enhance apoptosis-induced by cold atmospheric plasma via depletion of intracellular GSH and modification of oxidative stress. Cell Death Discov 2020; 6:83. [PMID: 32963811 PMCID: PMC7483448 DOI: 10.1038/s41420-020-00314-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/21/2020] [Accepted: 08/20/2020] [Indexed: 12/20/2022] Open
Abstract
Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O2• -) and hydroxyl radical (•OH). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.
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Affiliation(s)
- Paras Jawaid
- Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences University of Toyama, Toyama, Japan
| | - Mati Ur Rehman
- Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences University of Toyama, Toyama, Japan
| | - Qing-Li Zhao
- Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences University of Toyama, Toyama, Japan
| | - Masaki Misawa
- Theranostic Devices Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan
| | - Kenji Ishikawa
- Center for Low-temperature Plasma Science, Nagoya University, Nagoya, Japan
| | - Masaru Hori
- Center for Low-temperature Plasma Science, Nagoya University, Nagoya, Japan
| | - Tadamichi Shimizu
- Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences University of Toyama, Toyama, Japan
| | - Jun-ichi Saitoh
- Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences University of Toyama, Toyama, Japan
| | - Kyo Noguchi
- Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences University of Toyama, Toyama, Japan
| | - Takashi Kondo
- Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences University of Toyama, Toyama, Japan
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Ueno M, Nakanishi I, Matsumoto KI. Inhomogeneous generation of hydroxyl radicals in hydrogen peroxide solution induced by ultraviolet irradiation and in a Fenton reaction system. Free Radic Res 2020; 55:481-489. [PMID: 32896187 DOI: 10.1080/10715762.2020.1819995] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The density of hydroxyl radical (•OH) generation by degeneration of hydrogen peroxide (H2O2) during UVB irradiation and in a Fenton reaction system was estimated. The purpose of this study was to evaluate whether these reaction systems generate spatially uniform or inhomogeneous •OH from H2O2 in the reaction mixture. A series of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) solutions of several concentrations (0.13‒1661 mM) were prepared. For UVB irradiation, 1 μl of 98 mM, 980 mM, or 9.8 M H2O2 solution was added to a 100-μl aliquot of DMPO solution, and the reaction mixture was irradiated with UVB. For the Fenton reaction, 1 μl of 98 mM H2O2 and 1 μl of 100 mM FeSO4 were added to a 100-μl aliquot of DMPO solution. After UVB irradiation or adding FeSO4, the entire volume of the reaction mixture was drawn into PTFE tubing and measured by X-band EPR. The DMPO-OH concentration in the reaction mixture was plotted versus the molecular density of DMPO, and the density of •OH generation was estimated from an inflection point on the plotted profile. The local densities of the UV-induced •OH in the H2O2 water solutions depended on the concentration of H2O2 in the solution, and were likely localized. The energy absorption process of photons was suspected to occur in a step-wise manner in a limited volume. •OH generation in the Fenton reaction system was expected to be uniformly distributed, but inhomogeneous •OH generation was observed at the molecular level.
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Affiliation(s)
- Megumi Ueno
- Quantitative RedOx Sensing Group, Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Quantum Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
| | - Ikuo Nakanishi
- Quantitative RedOx Sensing Group, Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Quantum Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
| | - Ken-Ichiro Matsumoto
- Quantitative RedOx Sensing Group, Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Quantum Medical Science Directorate, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
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Yamakawa Y, Doi T, Naitou Y, Kawai H, Mitsumoto A, Kudo N, Kawashima Y. A single pretreatment with clofibric acid attenuates carbon tetrachloride-induced necrosis, but not steatosis, in rat liver. Food Chem Toxicol 2020; 145:111591. [PMID: 32739454 DOI: 10.1016/j.fct.2020.111591] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 06/19/2020] [Accepted: 07/08/2020] [Indexed: 01/14/2023]
Abstract
The present study investigated whether a single pretreatment with clofibric acid suppresses liver injury in rats after CCl4 intoxication. Rats received a single pretreatment with clofibric acid (100 mg/kg, i.p.) 1 h prior to a CCl4 (1 mL/kg, p.o.) challenge, and were euthanized 24 h after the CCl4 administration. A single pretreatment with clofibric acid effectively suppressed increases in the serum aminotransferase activities and the severity of necrosis following the CCl4 challenge, whereas the pretreatment did not protect against CCl4-induced fatty liver. The clofibric acid pretreatment did not affect blood concentrations of CCl4 in the early stage after CCl4 dosing, or the level of the CCl4 reaching the liver 1 h after the CCl4 challenge. Moreover, the clofibric acid pretreatment did not affect the intensity of the covalent binding of the [14C]CCl4 metabolite to microsomal proteins and lipids. The clofibric acid pretreatment did not alter microsomal cytochrome P450 2E1 activity. Based on these results, we conclude that protection against CCl4-induced hepatocellular necrosis by a clofibric acid pretreatment does not require its repeated administration, and that a single and brief pre-exposure to clofibric acid prior to CCl4 dosing markedly suppresses necrosis without affecting the development and progression of steatosis.
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Affiliation(s)
- Yoshihiro Yamakawa
- Research and Development Laboratories, Maruho Co, 1 Awatacho, Chudoji, Shimogyo-ku, Kyoto, 600-8815, Japan
| | - Takaaki Doi
- Research and Development Laboratories, Maruho Co, 1 Awatacho, Chudoji, Shimogyo-ku, Kyoto, 600-8815, Japan
| | - Yoshizumi Naitou
- Research and Development Laboratories, Maruho Co, 1 Awatacho, Chudoji, Shimogyo-ku, Kyoto, 600-8815, Japan
| | - Hiroshi Kawai
- Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Atsushi Mitsumoto
- Faculty of Pharmaceutical Sciences, Josai International University, Gumyo, Togane, Chiba, 283-8555, Japan
| | - Naomi Kudo
- Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Yoichi Kawashima
- Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
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Thuy LTT, Hai H, Kawada N. Role of cytoglobin, a novel radical scavenger, in stellate cell activation and hepatic fibrosis. Clin Mol Hepatol 2020; 26:280-293. [PMID: 32492766 PMCID: PMC7364355 DOI: 10.3350/cmh.2020.0037] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/09/2020] [Accepted: 03/13/2020] [Indexed: 12/17/2022] Open
Abstract
Cytoglobin (Cygb), a stellate cell-specific globin, has recently drawn attention due to its association with liver fibrosis. In the livers of both humans and rodents, Cygb is expressed only in stellate cells and can be utilized as a marker to distinguish stellate cells from hepatic fibroblast-derived myofibroblasts. Loss of Cygb accelerates liver fibrosis and cancer development in mouse models of chronic liver injury including diethylnitrosamine-induced hepatocellular carcinoma, bile duct ligation-induced cholestasis, thioacetamide-induced hepatic fibrosis, and choline-deficient L-amino acid-defined diet-induced non-alcoholic steatohepatitis. This review focuses on the history of research into the role of reactive oxygen species and nitrogen species in liver fibrosis and discusses the current perception of Cygb as a novel radical scavenger with an emphasis on its role in hepatic stellate cell activation and fibrosis.
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Affiliation(s)
- Le Thi Thanh Thuy
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Hoang Hai
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
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KARAKAYA B, KULOĞLU T, ÖNALAN E, KAYA TEKTEMUR N, DÖNDER E. Investigation of benfotiamine’s protective effects on liver tissue in experimental carbon tetrachloride induced liver injury. CUKUROVA MEDICAL JOURNAL 2020; 45:680-687. [DOI: 10.17826/cumj.676060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
Abstract
Purpose: In this study, we aimed to investigate the protective effects of benfotiamine on experimental liver injury caused by carbon tetrachloride (CCl4).Materials and Methods: In this study, 30 male Wistar albino rats were used. Rats were equally divided into 5 groups. No application was made to control group. The CCl4 group was injected i.p with1ml/kg CCl4:olive oil (1:2) mixture on the 1st and 8th days, and the CCl4+benfotiamine group was treated i.p with 1 ml/kg CCl4: olive oil (1:2) mixture twice on the 1st and 8th days and orally with 70 mg/kg/day benfotiamine. To the benfotiamine group, 70 mg/kg/day benfotiamine was given orally for 14 days. To the olive oil group, 2 ml/kg olive oil was given i.p. on 1st and 8th days. Finally, rats were decapitated. Liver tissues were removed and paraffin blocks were prepared. Tissues were stored at –80 oC for malonaldeyhde (MDA) assay.Results: There were no significant differences between the control, benfotiamine and olive oil groups. Compared with the control group, there was a significant increase in MDA, apoptosis and bax immunoreactivity in CCl4 group. Compared with the CCl4 group, there was a significant decrease in MDA, apoptosis and bax immunoreactivity in the CCl4+benfotiamine group.Conclusion: CCl4 increases MDA, apoptosis and bax immunoreactivity, and benfotiamine, given as treatment, reduces these parameters.
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Affiliation(s)
| | | | | | | | - Emir DÖNDER
- Fırat Üniversitesi Tıp Fakültesi İç Hastalıkları
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44
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Yoo DH, Lee JY. Anti-inflammatory Activities Verification of Ambrosia trifida L. extract in RAW 264.7 Cells. MICROBIOLOGY AND BIOTECHNOLOGY LETTERS 2020; 48:79-89. [DOI: 10.4014/mbl.1910.10004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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45
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Wang Z, Bai Y, Wang J, Wang J. The preventive and therapeutic effects of α-lipoic acid on ethylene glycol-induced calcium oxalate deposition in rats. Int Urol Nephrol 2020; 52:1227-1234. [DOI: 10.1007/s11255-020-02423-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 02/18/2020] [Indexed: 12/19/2022]
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46
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Pochkaeva EI, Podolsky NE, Zakusilo DN, Petrov AV, Charykov NA, Vlasov TD, Penkova AV, Vasina LV, Murin IV, Sharoyko VV, Semenov KN. Fullerene derivatives with amino acids, peptides and proteins: From synthesis to biomedical application. PROG SOLID STATE CH 2020. [DOI: 10.1016/j.progsolidstchem.2019.100255] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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47
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Effects of xylanase on growth performance, nutrients digestibility and intestinal health in weaned piglets. Livest Sci 2020. [DOI: 10.1016/j.livsci.2020.103940] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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48
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Crocus sativus L. Extract Containing Polyphenols Modulates Oxidative Stress and Inflammatory Response against Anti-Tuberculosis Drugs-Induced Liver Injury. PLANTS 2020; 9:plants9020167. [PMID: 32019201 PMCID: PMC7076685 DOI: 10.3390/plants9020167] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 01/16/2020] [Accepted: 01/17/2020] [Indexed: 02/07/2023]
Abstract
The purpose of this study is to analyze the polyphenolic rich extract of Crocus sativus L. petals (CSP) in modulating liver oxidative stress and inflammatory response status against rifampicin isoniazid (INH-RIF) drug-induced liver injury. The INH-RIF was administered for 14 days with varying doses in Wistar rats, while silymarin was administered as standard dose. We report the defensive impacts of CSP against INH-RIF induced liver oxidative stress and proinflammatory cytokine. The CSP treatment at both doses significantly controlled all modulating biochemical hepatic injury indicators and resulted in the attenuation of arbitral INH-RIF damage. The components present in CSP identified by LC–ESI-Q-TOF–MS were found to be flavonoids and fatty acids. It can be inferred that CSP possesses a hepatoprotective capacity against INH-RIF-mediated hepatic injury, which may prove to be a medically beneficial natural product for the management of drug-induced liver injury.
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49
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Alkadi H. A Review on Free Radicals and Antioxidants. Infect Disord Drug Targets 2020; 20:16-26. [PMID: 29952268 DOI: 10.2174/1871526518666180628124323] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 06/21/2018] [Accepted: 06/22/2018] [Indexed: 05/16/2023]
Abstract
Free radicals are generated in our body by several systems. A balance among free radicals and antioxidants is an important matter for appropriate physiological function. If free radicals become greater than the ability of the body to control them, a case known as oxidative stress appears, as a result of that, a number of human diseases spread in the body. Antioxidants can contribute to facingthis oxidative stress. The present review provides a brief overview of free radicals, oxidative stress, some natural antioxidants and the relationship between them.
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Affiliation(s)
- Hourieh Alkadi
- Department of Pharmaceutical Chemistry & Drug Control, Faculty of Pharmacy, Arab International University, Daraa, Syrian Arab Republic
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Oxidative Stress and Microvascular Alterations in Diabetic Retinopathy: Future Therapies. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:4940825. [PMID: 31814880 PMCID: PMC6878793 DOI: 10.1155/2019/4940825] [Citation(s) in RCA: 133] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 09/06/2019] [Accepted: 09/14/2019] [Indexed: 02/07/2023]
Abstract
Diabetes is a disease that can be treated with oral antidiabetic agents and/or insulin. However, patients' metabolic control is inadequate in a high percentage of them and a major cause of chronic diseases like diabetic retinopathy. Approximately 15% of patients have some degree of diabetic retinopathy when diabetes is first diagnosed, and most will have developed this microvascular complication after 20 years. Early diagnosis of the disease is the best tool to prevent or delay vision loss and reduce the involved costs. However, diabetic retinopathy is an asymptomatic disease and its development to advanced stages reduces the effectiveness of treatments. Today, the recommended treatment for severe nonproliferative and proliferative diabetic retinopathy is photocoagulation with an argon laser and intravitreal injections of anti-VEGF associated with, or not, focal laser for diabetic macular oedema. The use of these therapeutic approaches is severely limited, such as uncomfortable administration for patients, long-term side effects, the costs they incur, and the therapeutic effectiveness of the employed management protocols. Hence, diabetic retinopathy is the widespread diabetic eye disease and a leading cause of blindness in adults in developed countries. The growing interest in using polyphenols, e.g., resveratrol, in treatments related to oxidative stress diseases has spread to diabetic retinopathy. This review focuses on analysing the sources and effects of oxidative stress and inflammation on vascular alterations and diabetic retinopathy development. Furthermore, current and antioxidant therapies, together with new molecular targets, are postulated for diabetic retinopathy treatment.
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