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Mi P, Cao X, Feng H, Wang H. Association of blood cadmium levels with epigenetic age acceleration in U.S. adults aged > 50 years. Front Public Health 2025; 13:1504830. [PMID: 40302773 PMCID: PMC12037496 DOI: 10.3389/fpubh.2025.1504830] [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: 10/01/2024] [Accepted: 03/31/2025] [Indexed: 05/02/2025] Open
Abstract
Objectives DNA methylation (DNAm) is a sensitive biomarker of aging-related processes, and novel epigenetic-based "clocks" can estimate accelerated biological aging. Cadmium (Cd) can alter cellular processes that promote aging and disrupt global methylation patterns. However, few studies have investigated the association between blood Cd and accelerated aging. We aimed to investigate the association between blood Cd and four DNAm-based epigenetic age accelerations in individuals over 50 in the United States, using data from the National Health and Nutrition Examination Survey (NHANES). Methods DNAm-epigenetic biomarkers and blood Cd data from the NHANES database (1999-2002) were retrieved for this study. We evaluated four epigenetic ages: HorvathAge, HannumAge, PhenoAge, and GrimAge. Age acceleration was calculated by extracting the residuals from the regression of chronological age on each epigenetic age measure. We used weighted linear regression models and subgroup analyses to investigate the associations between blood Cd levels and these age accelerations, adjusting for potential confounding factors. Results Higher blood Cd levels (≥0.5 μg/dl) were significantly associated with increased age acceleration for PhenoAge (β = 1.37, P = 0.017) and GrimAge (β = 1.31, P = 0.003) in adjusted models. A significant association was also observed for HannumAge (β = 0.94, P = 0.016), although this association was not significant for continuous Cd levels (P = 0.111). No significant associations were found for HorvathAge. Subgroup analyses indicated consistent associations across demographic and lifestyle subgroups, with no significant interactions. Conclusions In this study, after adjusting for confounders, blood Cd levels were positively associated with PhenoAge acceleration and GrimAge acceleration in people over 50 in the United States. These results may be useful in proposing interventions in environmental exposures to slow the aging process and prevent age-related diseases.
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Affiliation(s)
- Panpan Mi
- Department of Orthopedic, Hebei PetroChina Central Hospital, Langfang, China
| | - Xu Cao
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Haixia Feng
- Department of Tuberculosis, Shandong Public Health Clinical Center, Jinan, Shandong, China
| | - Huijie Wang
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, China
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2
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Premraj A, Aleyas AG, Nautiyal B, Rasool TJ. First report of a chemokine from camelids: Dromedary CXCL8 is induced by poxvirus and heavy metal toxicity. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2024; 161:105261. [PMID: 39241936 DOI: 10.1016/j.dci.2024.105261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/27/2024] [Accepted: 09/02/2024] [Indexed: 09/09/2024]
Abstract
Low molecular weight proteins, known as chemokines, facilitate the migration and localization of immune cells to the site of infection and injury. One of the first chemokines identified, CXCL8 functions as a key neutrophil activator, recruiting neutrophils to sites of inflammation. Several viral infections, including zoonotic coronaviruses and poxviruses, have been reported to induce the expression of CXCL8. Dromedary camels are known to harbor several potentially zoonotic pathogens, but critical immune molecules such as chemokines remain unidentified. We report here the identification of CXCL8 from the dromedary camel - the first chemokine identified from camelids. The complete dromedary CXCL8 cDNA sequence as well as the corresponding gene sequence from dromedary and two New World camelids - alpaca and llama were cloned. CXCL8 mRNA expression was relatively higher in PBMC, spleen, lung, intestine, and liver. Poly(I:C) and lipopolysaccharide stimulated CXCL8 expression in vitro, while interferon treatment inhibited it. In vitro infection with potentially zoonotic camelpox virus induced the expression of CXCL8 in camel kidney cells. Toxicological studies on camelids have been limited, and no biomarkers have been identified. Hence, we also evaluated CXCL8 mRNA expression as a potential biomarker to assess heavy metal toxicity in camel kidney cells in vitro. CXCL8 expression was increased after in vitro exposure to heavy metal compounds of cobalt and cadmium, suggesting potential utility as a biomarker for renal toxicity in camels. The results of our study demonstrate that camel CXCL8 plays a significant role in immunomodulatory and induced toxicity responses in dromedary camels.
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Affiliation(s)
- Avinash Premraj
- Camel Biotechnology Center, Presidential Camels & Camel Racing Affairs Centre, Department of the President's Affairs, PO Box 17292, Al Ain, United Arab Emirates
| | - Abi George Aleyas
- Camel Biotechnology Center, Presidential Camels & Camel Racing Affairs Centre, Department of the President's Affairs, PO Box 17292, Al Ain, United Arab Emirates
| | - Binita Nautiyal
- Camel Biotechnology Center, Presidential Camels & Camel Racing Affairs Centre, Department of the President's Affairs, PO Box 17292, Al Ain, United Arab Emirates
| | - Thaha Jamal Rasool
- Camel Biotechnology Center, Presidential Camels & Camel Racing Affairs Centre, Department of the President's Affairs, PO Box 17292, Al Ain, United Arab Emirates.
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3
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Zhang Y, Liu M, Xie R. Associations between cadmium exposure and whole-body aging: mediation analysis in the NHANES. BMC Public Health 2023; 23:1675. [PMID: 37653508 PMCID: PMC10469832 DOI: 10.1186/s12889-023-16643-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 08/29/2023] [Indexed: 09/02/2023] Open
Abstract
INTRODUCTION Even though cadmium (Cd) exposure and cellular senescence (telomere length) have been linked in previous studies, composite molecular aging biomarkers are more significant and reliable factors to consider when examining the connection between metal exposure and health outcomes. The purpose of this research was to assess the association between urinary cadmium (U-Cd) and whole-body aging (phenotypic age). METHODS Phenotypic age was calculated from chronological age and 9 molecular biomarkers. Multivariate linear regression models, subgroup analysis, and smoothing curve fitting were used to explore the linear and nonlinear relationship between U-Cd and phenotypic age. Mediation analysis was performed to explore the mediating effect of U-Cd on the association between smoking and phenotypic age. RESULTS This study included 10,083 participants with a mean chronological age and a mean phenotypic age of 42.24 years and 42.34 years, respectively. In the fully adjusted model, there was a positive relationship between U-Cd and phenotypic age [2.13 years per 1 ng/g U-Cd, (1.67, 2.58)]. This association differed by sex, age, and smoking subgroups (P for interaction < 0.05). U-Cd mediated a positive association between serum cotinine and phenotypic age, mediating a proportion of 23.2%. CONCLUSIONS Our results suggest that high levels of Cd exposure are associated with whole-body aging.
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Affiliation(s)
- Ya Zhang
- Department of Gland Surgery, The Affiliated Nanhua Hospital, Hengyang Medical school, University of South China, Hengyang, 421002, China
| | - Mingjiang Liu
- Department of Hand & Microsurgery, The Affiliated Nanhua Hospital, Hengyang Medical school, University of South China, No.336 Dongfeng South Road, Zhuhui District, Hunan Province, Hengyang, 421002, China
| | - Ruijie Xie
- Department of Hand & Microsurgery, The Affiliated Nanhua Hospital, Hengyang Medical school, University of South China, No.336 Dongfeng South Road, Zhuhui District, Hunan Province, Hengyang, 421002, China.
- Hengyang Medical school, University of South China, Hengyang, 421002, China.
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4
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Kaden T, Graf K, Rennert K, Li R, Mosig AS, Raasch M. Evaluation of drug-induced liver toxicity of trovafloxacin and levofloxacin in a human microphysiological liver model. Sci Rep 2023; 13:13338. [PMID: 37587168 PMCID: PMC10432496 DOI: 10.1038/s41598-023-40004-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 08/03/2023] [Indexed: 08/18/2023] Open
Abstract
Drug-induced liver injury induced by already approved substances is a major threat to human patients, potentially resulting in drug withdrawal and substantial loss of financial resources in the pharmaceutical industry. Trovafloxacin, a broad-spectrum fluoroquinolone, was found to have unexpected side effects of severe hepatotoxicity, which was not detected by preclinical testing. To address the limitations of current drug testing strategies mainly involving 2D cell cultures and animal testing, a three-dimensional microphysiological model of the human liver containing expandable human liver sinusoidal endothelial cells, monocyte-derived macrophages and differentiated HepaRG cells was utilized to investigate the toxicity of trovafloxacin and compared it to the structurally-related non-toxic drug levofloxacin. In the model, trovafloxacin elicited vascular and hepatocellular toxicity associated with pro-inflammatory cytokine release already at clinically relevant concentrations, whereas levofloxacin did not provoke tissue injury. Similar to in vivo, cytokine secretion was dependent on a multicellular immune response, highlighting the potential of the complex microphysiological liver model for reliably detecting drug-related cytotoxicity in preclinical testing. Moreover, hepatic glutathione depletion and mitochondrial ROS formation were elucidated as intrinsic toxicity mechanisms contributing to trovafloxacin toxicity.
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Affiliation(s)
- Tim Kaden
- Dynamic42 GmbH, Jena, Germany
- Institute of Biochemistry II, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany
| | | | | | - Ruoya Li
- Biopredic International, St Gregoire, France
| | - Alexander S Mosig
- Institute of Biochemistry II, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany
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Akash MSH, Yaqoob A, Rehman K, Imran M, Assiri MA, Al-Rashed F, Al-Mulla F, Ahmad R, Sindhu S. Metabolomics: a promising tool for deciphering metabolic impairment in heavy metal toxicities. Front Mol Biosci 2023; 10:1218497. [PMID: 37484533 PMCID: PMC10357477 DOI: 10.3389/fmolb.2023.1218497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 06/21/2023] [Indexed: 07/25/2023] Open
Abstract
Heavy metals are the metal compounds found in earth's crust and have densities higher than that of water. Common heavy metals include the lead, arsenic, mercury, cadmium, copper, manganese, chromium, nickel, and aluminum. Their environmental levels are consistently rising above the permissible limits and they are highly toxic as enter living systems via inhalation, ingestion, or inoculation. Prolonged exposures cause the disruption of metabolism, altered gene and/or protein expression, and dysregulated metabolite profiles. Metabolomics is a state of the art analytical tool widely used for pathomolecular inv22estigations, biomarkers, drug discovery and validation of biotransformation pathways in the fields of biomedicine, nutrition, agriculture, and industry. Here, we overview studies using metabolomics as a dynamic tool to decipher the mechanisms of metabolic impairment related to heavy metal toxicities caused by the environmental or experimental exposures in different living systems. These investigations highlight the key role of metabolomics in identifying perturbations in pathways of lipid and amino acid metabolism, with a critical role of oxidative stress in metabolic impairment. We present the conclusions with future perspectives on metabolomics applications in meeting emerging needs.
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Affiliation(s)
| | - Azka Yaqoob
- Department of Pharmaceutical Chemistry, Government College University Faisalabad, Faisalabad, Pakistan
| | - Kanwal Rehman
- Department of Pharmacy, The Women University, Multan, Pakistan
| | - Muhammad Imran
- Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia
- Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia
| | - Mohammed A. Assiri
- Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha, Saudi Arabia
- Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia
| | - Fatema Al-Rashed
- Immunology and Microbiology Department, Dasman Diabetes Institute, Dasman, Kuwait
| | - Fahd Al-Mulla
- Research Division, Dasman Diabetes Institute, Dasman, Kuwait
| | - Rasheed Ahmad
- Immunology and Microbiology Department, Dasman Diabetes Institute, Dasman, Kuwait
| | - Sardar Sindhu
- Immunology and Microbiology Department, Dasman Diabetes Institute, Dasman, Kuwait
- Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman, Kuwait
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Mizuno Y, Inaba Y, Masuoka H, Kibe M, Kosaka S, Natsuhara K, Hirayama K, Inthavong N, Kounnavong S, Tomita S, Umezaki M. Determinants of oxidative stress among indigenous populations in Northern Laos: Trace element exposures and dietary patterns. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 868:161516. [PMID: 36646220 DOI: 10.1016/j.scitotenv.2023.161516] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 01/06/2023] [Accepted: 01/06/2023] [Indexed: 06/17/2023]
Abstract
OBJECTIVES To investigate determinants of oxidative stress in an indigenous population, we examined associations of trace element exposures and dietary patterns with three oxidative stress-related biomarkers among indigenous populations in Northern Laos. METHODS This cross-sectional study included 341 adults from three villages with different levels of modernization. We used three oxidative stress-related biomarkers: urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane concentrations, which were measured using liquid chromatography-tandem mass spectrometry, and blood telomere lengths, which were measured using a quantitative polymerase chain reaction method. We used multilevel analysis to examine associations of urinary arsenic, cadmium, and selenium concentrations, their interaction terms, and wild-plant-food scores (principal component scores calculated from food consumption frequencies) with oxidative stress-related biomarkers. RESULTS Urinary arsenic and cadmium concentrations were positively associated with urinary 8-isoprostane concentrations. Urinary selenium concentrations were positively associated with urinary 8-OHdG concentrations. Interaction terms ([arsenic or cadmium] × selenium) showed negative associations with urinary 8-OHdG and 8-isoprostane concentrations, respectively. Urinary cadmium concentrations were negatively associated with telomere lengths. Wild-plant-food scores did not exhibit associations with oxidative stress-related biomarkers. CONCLUSION Our findings imply that exposure to arsenic and cadmium is associated with greater oxidative lipid damage, whereas selenium may attenuate arsenic-induced oxidative DNA damage and cadmium-induced oxidative lipid damage. Cadmium exposure may accelerate telomere attrition. Trace element exposure may be a determinant of oxidative stress among indigenous populations in Northern Laos.
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Affiliation(s)
- Yuki Mizuno
- Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Yohei Inaba
- Department of Environmental Health, National Institute of Public Health, Saitama, Japan.
| | - Hiroaki Masuoka
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
| | - Mihoko Kibe
- Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Satoko Kosaka
- Department of Public Health & Nursing, Nagasaki University, Nagasaki, Japan.
| | | | - Kazuhiro Hirayama
- Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
| | - Nouhak Inthavong
- Lao Tropical and Public Health Institute, Ministry of Health, Vientiane, Lao Democratic People's Republic
| | - Sengchanh Kounnavong
- Lao Tropical and Public Health Institute, Ministry of Health, Vientiane, Lao Democratic People's Republic
| | - Shinsuke Tomita
- Graduate School of Environmental Studies, Nagoya University, Nagoya, Japan.
| | - Masahiro Umezaki
- Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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7
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Malik S, Awan SJ, Farzand A, Ali Q. Inflammation reduction potential of nanostructured lipid carriers encapsulated with rat's bone marrow cells' lysate. BRAZ J BIOL 2023; 82:e269553. [PMID: 36629549 DOI: 10.1590/1519-6984.269553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 12/01/2022] [Indexed: 01/11/2023] Open
Abstract
Bone marrow-derived mesenchymal stromal cells (BMSCs) have been used for treating inflammatory disorders. Due to the large size of BMSCs compared to nanoparticles, BMSCs cannot be loaded into the nanoparticles. It is hypothesized that BMSCs lysate loading into the nanocarriers will effectively deliver cellular contents and regulatory elements of BMSCs at the injury site. This study aimed to investigate nanostructured lipid carriers (NLC) loading with BMSCs lysate through basic characterization and morphological analysis. Moreover, this study was mainly designed to investigate the role of NLC loaded BMSCs lysate in reducing inflammation via in-vitro and in-vivoassays. The in-vitro study involves cell viability assays, p53, annexin V and VEGF expression through ELISA and immunocytochemistry, real-time BAX, caspase-3, IL-6, IL-8, TOP2A, PCNA, and Ki-67 gene expression analysis. Additionally, to evaluate in-vivo anti-inflammatory activity, the carrageenan-induced rat paw oedema model was used. In-vitro results showed that NLC loaded BMSCs lysate increased cell viability, decreased apoptosis and pro-inflammatory genes expression and up-regulated angiogenesis and proliferation in H2O2 pre-stimulated cells. Findings of the in-vivo assay also indicated a reduction in rat's paw oedema volume in NLC-loaded BMSCs lysate, and downregulation of BAX, Caspase-3, IL-6, and IL-8 was observed. Enhanced expressions of TOP2A, PCNA, and Ki-67 were obtained. Concluding the results of this study, NLC-loaded BMSCs lysate could reduce inflammation and possibly regenerate damaged tissue mainly via increasing cell viability, angiogenesis and proliferation, and reducing apoptosis and pro-inflammatory cytokines.
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Affiliation(s)
- S Malik
- The University of Lahore, Institute of Molecular Biology and Biotechnology - IMBB, Lahore, Pakistan
| | - S J Awan
- The University of Lahore, Institute of Molecular Biology and Biotechnology - IMBB, Lahore, Pakistan.,Kinnaird College For Women, Department of Zoology, Lahore, Pakistan
| | - A Farzand
- The University of Lahore, Institute of Molecular Biology and Biotechnology - IMBB, Lahore, Pakistan
| | - Q Ali
- University of the Punjab, Department of Plant Breeding and Genetics, Lahore, Pakistan
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8
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Kim C, Cathey AL, Watkins DJ, Mukherjee B, Rosario-Pabón ZY, Vélez-Vega CM, Alshawabkeh AN, Cordero JF, Meeker JD. Maternal blood metal concentrations are associated with matrix metalloproteinases (MMPs) among pregnant women in Puerto Rico. ENVIRONMENTAL RESEARCH 2022; 209:112874. [PMID: 35123972 PMCID: PMC10443181 DOI: 10.1016/j.envres.2022.112874] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/28/2022] [Accepted: 01/29/2022] [Indexed: 06/11/2023]
Abstract
BACKGROUND/AIM Matrix metalloproteinases (MMPs) are important regulators of uterine remodeling, a critical process for healthy pregnancies, and studies have revealed a link between an imbalance in MMPs and adverse birth outcomes. Toxicological studies have indicated that exposure to heavy metals can alter the levels of inflammatory cytokines, including MMPs. Despite growing evidence, the clear association between heavy metal exposure and MMPs has yet to be explored extensively in human populations. To have a better understanding of the association, in this study, we assessed associations between maternal blood metal levels with MMPs among 617 pregnant women in the Puerto Rico PROTECT birth cohort. METHODS We measured blood concentrations for 11 metals in the first and/or second trimester of pregnancy using ICP-MS. MMPs (MMP1, MMP2, and MMP9) were quantified using a customized Luminex assay. Linear mixed effects models (LMEs) were used to regress MMPs on metals and included random intercepts for study participants to account for correlated repeated outcome measures. Fetal sex effects were estimated using interaction terms between metal exposure variables and fetal sex indicators. RESULTS We observed significant associations between cesium, manganese, and zinc with all the MMPs that were measured. We also observed differences in metal-MMPs associations by fetal sex. Cobalt was positively associated with MMP1 only in women with male fetuses, and cesium was negatively associated with MMP1 only in women with female fetuses. MMP2 had significant associations with maternal blood metal concentrations only in women with female fetuses. CONCLUSION Certain metals were significantly associated with MMPs that are responsible for uterine remodeling and healthy pregnancies. Most of these associations differed by fetal sex. This study highlighted significant metal-MMPs associations that may inform research on new avenues for understanding heavy metal-induced adverse birth outcomes and the development of diagnostic tools.
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Affiliation(s)
- Christine Kim
- University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI, United States
| | - Amber L Cathey
- University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI, United States
| | - Deborah J Watkins
- University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI, United States
| | - Bhramar Mukherjee
- University of Michigan School of Public Health, Department of Biostatistics, Ann Arbor, MI, United States
| | - Zaira Y Rosario-Pabón
- University of Puerto Rico Graduate School of Public Health, UPR Medical Sciences Campus, San Juan, PR, USA
| | - Carmen M Vélez-Vega
- University of Puerto Rico Graduate School of Public Health, UPR Medical Sciences Campus, San Juan, PR, USA
| | | | - José F Cordero
- Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA, United States
| | - John D Meeker
- University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, MI, United States.
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Zhang J, Feng W, Li M, Chen P, Ning X, Ou C, Chen M. Receptor-Interacting Protein Kinase 3 Inhibition Prevents Cadmium-Mediated Macrophage Polarization and Subsequent Atherosclerosis via Maintaining Mitochondrial Homeostasis. Front Cardiovasc Med 2021; 8:737652. [PMID: 34820428 PMCID: PMC8606644 DOI: 10.3389/fcvm.2021.737652] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 09/28/2021] [Indexed: 12/11/2022] Open
Abstract
Chronic cadmium (Cd) exposure contributes to the progression of cardiovascular disease (CVD), especially atherosclerosis (AS), but the underlying mechanism is unclear. Since mitochondrial homeostasis is emerging as a core player in the development of CVD, it might serve as a potential mechanism linking Cd exposure and AS. In this study, we aimed to investigate Cd-mediated AS through macrophage polarization and know the mechanisms of Cd-caused mitochondrial homeostasis imbalance. In vitro, flow cytometry shows that Cd exposure promotes M1-type polarization of macrophages, manifested as the increasing expressions of nuclear Factor kappa-light-chain-enhancer of activated B (NF-kB) and NLR family pyrin domain containing 3 (NLRP3). Mitochondrial homeostasis tests revealed that decreasing mitochondrial membrane potential and mitophage, increasing the mitochondrial superoxide (mROS), and mitochondrial fission are involved in the Cd-induced macrophage polarization. The upregulated expressions of receptor-interacting protein kinase 3 (RIPK3) and pseudokinase-mixed lineage kinase domain-like protein (p-MLKL) were observed. Knocking out RIPK3, followed by decreasing the expression of p-MLKL, improves the mitochondrial homeostasis imbalance which effectively reverses macrophage polarization. In vivo, the oil red O staining showed that Cd with higher blood significantly aggravates AS. Besides, M1-type polarization of macrophages and mitochondrial homeostasis imbalance were observed in the aortic roots of the mice through immunofluorescence and western blot. Knocking out RIPK3 restored the changes above. Finally, the administered N-acetyl cysteine (NAC) or mitochondrial division inhibitor-1 (Mdivi-1), which decreased the mROS or mitochondrial fission, inhibited the expressions of RIPK3 and p-MLKL, attenuating AS and macrophage M1-type polarization in the Cd-treated group. Consequently, the Cd exposure activated the RIPK3 pathway and impaired the mitochondrial homeostasis, resulting in pro-inflammatory macrophage polarization and subsequent AS. Knocking out RIPK3 provided a potential therapeutic target for Cd-caused macrophage polarization and subsequent AS.
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Affiliation(s)
- Jiexin Zhang
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China
| | - Weijing Feng
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China.,Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Minghui Li
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China
| | - Peier Chen
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China
| | - Xiaodong Ning
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China
| | - Caiwen Ou
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China
| | - Minsheng Chen
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China
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10
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Bakdemir M, Çetin E. Hepatoprotective effects of ethyl pyruvate against carbon tetrachloride-induced oxidative stress, biochemical and histological alterations in rats. Arch Physiol Biochem 2021; 127:359-366. [PMID: 31314597 DOI: 10.1080/13813455.2019.1640254] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
This study investigated the protective effects of ethyl pyruvate (EP) against carbon tetrachloride (CCl4)-induced acute hepatic injury in rats. The administration of a single dose of CCl4 (1.6 g/kg body weight) significantly elevated the levels of malondialdehyde, nitric oxide, alanine transaminase, aspartate transaminase, and alkaline phosphatase, cholesterol, low-density lipoprotein cholesterol, and triglycerides. In addition, CCl4 was found to significantly suppress the activity of superoxide dismutase, catalase, and glutathione peroxidase. All of these parameters were restored to their normal levels by the administration of EP before and after the CCl4 injection. Moreover, the number of positive apoptotic hepatocytes had significantly increased in the CCl4 group but decreased in rats treated with EP along with CCl4. Histopathological changes induced by CCl4 were also ameliorated by EP treatment. These findings provided evidence that EP, because of its antioxidant and anti-apoptotic action, could protect rat liver against CCl4-induced acute liver injury.
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Affiliation(s)
- Miraç Bakdemir
- Department of Veterinary Physiology, Institute of Health Sciences, Erciyes University, Kayseri, Turkey
| | - Ebru Çetin
- Department of Physiology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Turkey
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11
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Goyal T, Mitra P, Singh P, Ghosh R, Lingeswaran M, Sharma S, Purohit P, Sharma P. Estimation of lymphocyte subsets and cytokine levels in workers occupationally exposed to cadmium. J Trace Elem Med Biol 2021; 64:126681. [PMID: 33248335 DOI: 10.1016/j.jtemb.2020.126681] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/24/2020] [Accepted: 11/06/2020] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Occupational exposure to Cadmium (Cd) may have serious health effect on workers. However, little is known about its effect on immune system. Moreover, previous studies have been inconclusive in stating the effect of Cd on immune system. The aim of our study was to estimate immune parameters in workers occupationally exposed to Cd. MATERIAL AND METHODS 110 individuals occupationally exposed to Cd and 97 apparently healthy non-exposed individuals were recruited for this study. Blood Cadmium levels were determined by AAS. Lymphocyte subset were analyzed using flow cytometry and the cytokine levels were determined by ELISA. RESULTS Exposed group have significantly higher levels of B-Cd. % of CD8 cells were higher in exposed while % of CD4 cells showed a decreasing trend in the exposed group. Among the CD3CD4 T cell subsets Th1 (%) and Tregs (%) cells were lower while Th17 (%) were higher in exposed group. Increased levels of IL-4 (Th2), IL-6 (Th2) and TNF- α (Th1) and decreased levels of IL-2 (Th1) and IL-10 (Tregs) were observed in Cd exposed workers which is indicative of a predominant pro-inflammatory response in Cd exposed workers. IL-17 (Th17) levels did not show any significant difference between the two groups. Increased Th17/Tregs ratio in the exposed group is also suggestive of an increased pro-inflammatory immune response in exposed group. CONCLUSION To conclude, even low level of exposure to Cd in occupational settings is associated with alterations in Th17 cells, which may further predispose an individual to other systemic abnormalities.
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Affiliation(s)
- Taru Goyal
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.
| | - Prasenjit Mitra
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.
| | - Preeti Singh
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.
| | - Raghumoy Ghosh
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.
| | - Malavika Lingeswaran
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.
| | - Shailja Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.
| | - Purvi Purohit
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.
| | - Praveen Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.
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12
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He Q, Luo Y, Xie Z. Sulforaphane ameliorates cadmium induced hepatotoxicity through the up-regulation of /Nrf2/ARE pathway and the inactivation of NF-κB. J Funct Foods 2021. [DOI: 10.1016/j.jff.2020.104297] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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13
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14
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Quinete N, Hauser-Davis RA. Drinking water pollutants may affect the immune system: concerns regarding COVID-19 health effects. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:1235-1246. [PMID: 33156499 PMCID: PMC7644792 DOI: 10.1007/s11356-020-11487-4] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 10/30/2020] [Indexed: 05/12/2023]
Abstract
The current coronavirus pandemic is leading to significant impacts on the planet, changing our way of life. Although the COVID-19 virus mechanisms of action and pathogenesis are still under extensive research, immune system effects are evident, leading, in many cases, to respiratory distress. Although apparent pollution reduction has been noticed by the population, environmental and human health impacts due to the increased use of plastic waste and disinfectants is concerning. One of the main routes of human exposure to pollutants is through drinking water. Thus, this point of view discusses some major contaminants in drinking water known to be immunotoxic, exploring sources and drinking water routes and emphasizing the known mechanisms of action that could likely compromise the effective immune response of humans, particularly raising concerns regarding people exposed to the COVID-19 virus. Based on a literature review, metals, plastic components, plasticizers, and per- and polyfluoroalkyl substances may display the potential to exacerbate COVID-19 respiratory symptoms, although epidemiological studies are still required to confirm the synergistic effects between these pollutants and the virus.
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Affiliation(s)
- Natalia Quinete
- Institute of Environment & Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Modesto A. Maidique Campus, Miami, FL, 33199, USA.
| | - Rachel Ann Hauser-Davis
- Laboratório de Avaliação e Promoção da Saúde Ambiental, Instituto Oswaldo Cruz, Fiocruz, Av. Brazil, 4.365, Manguinhos, Rio de Janeiro, RJ, 21040-360, Brazil
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15
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Zhang X, Liu R. Advances in BPA-induced Oxidative Stress and Related Effects and Mechanisms in Liver, 1991-2017. Mini Rev Med Chem 2020; 20:432-443. [PMID: 30207228 DOI: 10.2174/1389557518666180912105345] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 07/27/2018] [Accepted: 07/31/2018] [Indexed: 12/15/2022]
Abstract
Bisphenol A (BPA) is a widely spreading environmental endocrine disruptor . Its characteristics, including small doses and frequent contact, make it easy to enter human body through drinking water, food, air and other pathways, leading to tumors, infertility, and liver damage. The present review summarizes the underlying mechanism of oxidative stress and its related effects induced by BPA in the liver. The progress of the mechanism for oxidative stress induced by BPA is summarized, including mitochondrial dysfunction, lipid peroxidation and inflammation reaction, liver dyslipidemia, apoptosis, and cell death mechanism. In the future, it is necessary to elucidate the molecular mechanisms and timing of oxidative stress to clarify the effects on different exposures to different genders and growth stages. Besides, studying the toxic effects on BPA surrogates, BPA metabolites and BPA combined with other pollutants in the environment is beneficial to clarify the environmental and human health effects of BPA and provide technical reference for the development of practical control measures.
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Affiliation(s)
- Xun Zhang
- School of Environmental Science and Engineering, Shandong University, China -America CRC for Environment & Health, Shandong Province, 27# Shanda South Road, Jinan 250100, China
| | - Rutao Liu
- School of Environmental Science and Engineering, Shandong University, China -America CRC for Environment & Health, Shandong Province, 27# Shanda South Road, Jinan 250100, China.,Department of Chemistry and Chemical Engineering, Qilu Normal University, Jinan 250013, China
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16
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Khan IS, Dar KB, Ganie SA, Ali MN. Toxicological impact of sodium benzoate on inflammatory cytokines, oxidative stress and biochemical markers in male Wistar rats. Drug Chem Toxicol 2020; 45:1345-1354. [PMID: 33003957 DOI: 10.1080/01480545.2020.1825472] [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: 12/13/2022]
Abstract
Sodium benzoate is a widely used food and pharmaceutical preservative due to its antibacterial and antifungal activity. In the present study effect of different concentrations of sodium benzoate on hepatic antioxidants, inflammatory cytokines (TNF-α, IFN-γ, IL-1β and IL-6), biochemical markers and histopathology of liver was evaluated. Twenty five adult rats (aged 1-2 months) with 5 rats per group were randomly distributed into 5 groups. Group 1 rats were used as control and all groups (1-5) were provided with water and fed ad libitum. In addition to usual water and food, rats of group 2, 3, 4 and 5 were treated with 70, 200, 400 and 700 mg/kg b.wt of sodium benzoate once a day via oral gavage for 30 days. Our results showed that activity of glutathione peroxidase (GPx), catalase (CAT), glutathione-s-transferase (GST), glutathione reductase (GR) and superoxide dismutase (SOD) in rats decreased significantly when treated with 200, 400 and 700 mg/kg b.wt of sodium benzoate. Increase in the concentration of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum total protein, albumin, globulin, urea and creatinine was found to be dose dependent. Severe histopathological damage was observed in the hepatic tissue at higher concentrations of sodium benzoate. It was noticed that high concentrations of sodium benzoate (200, 400 and 700 mg/kg b.wt) produce significant increase in inflammatory cytokine markers (TNF-α, IFN-γ, IL-1β and IL-6) in comparison to control. Sodium benzoate at concentration of 70 mg/kg b.wt did not produce any significant changes in any of the above studied parameters.
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Affiliation(s)
- Ishfaq Shafi Khan
- Cytogenetics and Molecular Biology Research Laboratory, Centre of Research for Development, University of Kashmir, Srinagar, India.,Department of Clinical Biochemistry, University of Kashmir, Srinagar, India
| | - Khalid Bashir Dar
- Department of Clinical Biochemistry, University of Kashmir, Srinagar, India
| | | | - Md Niamat Ali
- Cytogenetics and Molecular Biology Research Laboratory, Centre of Research for Development, University of Kashmir, Srinagar, India
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17
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Usende IL, Olopade JO, Emikpe BO, Nafady AAHM. Biochemical and ultrastructural changes in kidney and liver of African Giant Rats (Cricetomysgambianus, Waterhouse, 1840) exposed to intraperitoneal sodium metavanadate (vanadium) intoxication. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2020; 79:103414. [PMID: 32442722 DOI: 10.1016/j.etap.2020.103414] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 04/28/2020] [Accepted: 05/17/2020] [Indexed: 06/11/2023]
Abstract
We studied the hepatic and renal impact of sodium metavanadate (SMV) exposure in African giant rats (AGR). Twelve male AGR were used and divided into two groups. The control group received sterile water while the SMV-exposed group received 3 mg/kg SMV intraperitoneally for 14 days. SMV exposed AGR groups showed significantly decreased activities of serum AST, ALT, ALP and creatinine concentration but increased blood urea nitrogen (BUN), albumin and globulin concentrations. Kidney ultrastructure examination revealed atrophy of the glomerular tuft, loss of podocytes, distortions of the endothelium and glomerular basement membrane. The liver sinusoids fenestration phenotypes were abnormal. Hepatocytes exhibited hypertrophy with uneven, crenated and dentate nuclei. SMV exposure induced activation of monocytes, as well as Kupffer and fibrous cells. Alterations in glomerular podocytes and cell-cell and cell matrix contact and inflammatory liver fibrosis are key events in progressive glomerular failure and hepatic damage due to SMV intoxication.
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Affiliation(s)
- Ifukibot Levi Usende
- Department of Veterinary Anatomy, University of Abuja, Nigeria; Department of Veterinary Anatomy, University of Ibadan, Nigeria
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18
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Rezk MM, Dhmees AS, Abd El-Magied M, Manaa ESA, El-Gendy HS. The influence of cobalt manganese ferrite nanoparticles (Co 0.5Mn 0.5Fe 2O 4) on reduction of hazardous effects of vanadate in adult rats. Toxicol Res (Camb) 2020; 9:81-90. [PMID: 32440339 PMCID: PMC7233316 DOI: 10.1093/toxres/tfaa007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Revised: 02/04/2020] [Accepted: 02/25/2020] [Indexed: 11/14/2022] Open
Abstract
Effect of cobalt manganese ferrite nanoparticles (M-NPs) (Co0.5Mn0.5Fe2O4) on vanadium hazards was assessment in the present study. Four groups of adult male albino rats [control group and three variably treated groups with ammonium metavanadate accompanied with or without cobalt M-NPs] were studied. The oral administration of ammonium metavanadate (Am.V) (20 mg/kg b.wt.) demonstrated the facility of vanadium to distribute and accumulate in the distinctive body organs and ordered as kidney > liver > lung > brain > spleen. Also, Am.V administration induce a significant disturbance in many physiological parameters (RBS, cholesterol, triglyceride, aspartate transaminase, alanine transaminase, Alb., bilirubin, Alk.Ph., urea, creat., Hb%, red blood cell count and packed cell volume) which might be expected to the liberation of free radicals according to the vanadium intoxication or its ability to disturb many body metabolisms. On the other hand, the intraperitoneal administration of 5% M-NPs in parallel with Am.V orally administration showed the ability of M-NPs to reduce Am.V dangerous impacts, which might be resulted from the essentiality of M-NPs metals to the body metabolism and to its free radicals scavenging properties. So, M-NPs could reduce Am.V hazardous effects.
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Affiliation(s)
- Mohamed M Rezk
- Isotopes Department, Nuclear Materials Authority, P.O. Box 530, El Maadi, Cairo 11936, Egypt
| | - Abdelghaffar S Dhmees
- Department of Analysis and Evaluation, Egyptian Petroleum Research Institute, 11727, Cairo, Egypt
| | - Mahmoud O Abd El-Magied
- Isotopes Department, Nuclear Materials Authority, P.O. Box 530, El Maadi, Cairo 11936, Egypt
| | - El-Sayed A Manaa
- Isotopes Department, Nuclear Materials Authority, P.O. Box 530, El Maadi, Cairo 11936, Egypt
| | - Hassan S El-Gendy
- Isotopes Department, Nuclear Materials Authority, P.O. Box 530, El Maadi, Cairo 11936, Egypt
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19
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Slivinska LG, Shcherbatyy AR, Lukashchuk BO, Gutyj BV. The state of antioxidant protection system in cows under the influence of heavy metals. REGULATORY MECHANISMS IN BIOSYSTEMS 2020. [DOI: 10.15421/022035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
A highly relevant problem of modern veterinary science is the study of features and mechanisms of combined action of the most common heavy metals – cadmium and plumbum and their influence on the body of humans and animals in the regions of Ukraine under technogenic pollution. The purpose of the work was to study the influence of heavy metals on the state of the antioxidant protection system of cows, in particular on the content of lipid peroxidation products (malonic dialdehyde, lipid hydroperoxides and diene conjugates), and activity of antioxidant enzymes (glutathione peroxidase and superoxide dismutase), depending on the distance to the heaps of mines in the coal basin. The study objects were cows of black-and-white breed at the age of 3–7 years. It was established that this parameter in the place with the highest concentration of diene conjugates in the blood of cows was by 25.8 % higher compared to the place of low concentration and 12.1 % higher compared to the place with medium concentration. In the place with the highest content of lipid hydroperoxides in the blood of cows the parameter was 23.7 % higher compared to the cows from the place with the low content. The concentration of lipid hydroperoxides in the blood of cows from the place with the medium content was 16.7% higher compared to the cows from the place with the low content. The parameter from the place with the lowest content of lipid hydroperoxides in the blood of cows was 12.1% lower compared to the place with the highest content. The level of malonic dialdehyde in the blood of cows from the technogenic pollution zone in the place with the largest amount was higher by 36.2; 34.0 and 18.8 % – compared to places with medium and low levels, respectively. The activity of superoxide dismutase in the blood of cows in the place with its highest activity was 0.284 ± 0.0099 % block. reac/g Hb, and in the place with the lowest activity – 0.23 ± 0.0051 % block. reac/g Hb. The activity of glutathione peroxidase in the blood of cows in farms of the technogenic pollution zone depended on the distance to the mine. These researches will further develop effective methods of treating cows under the influence of heavy metals, in particular regarding the antioxidant system.
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20
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Xin R, Pan YL, Wang Y, Wang SY, Wang R, Xia B, Qin RN, Fu Y, Wu YH. Nickel-refining fumes induce NLRP3 activation dependent on mitochondrial damage and ROS production in Beas-2B cells. Arch Biochem Biophys 2019; 676:108148. [DOI: 10.1016/j.abb.2019.108148] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 09/29/2019] [Accepted: 10/09/2019] [Indexed: 12/23/2022]
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21
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Zhang L, Song L, Liu B, Wu M, Wang L, Zhang B, Xiong C, Xia W, Li Y, Cao Z, Wang Y, Xu S. Prenatal cadmium exposure is associated with shorter leukocyte telomere length in Chinese newborns. BMC Med 2019; 17:27. [PMID: 30722777 PMCID: PMC6364384 DOI: 10.1186/s12916-019-1262-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 01/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Newborn telomere length (TL) is considered a potential marker for future disease and lifelong health, but few epidemiological studies have examined the determinants of TL in early life. The study aim was to investigate whether there is an association between prenatal cadmium exposure and relative cord blood TL in Chinese newborns. METHODS Participants were 410 mother-newborn pairs drawn from a prospective birth cohort study conducted in Wuhan, China, between November 2013 and March 2015. Urine samples were collected from pregnant women during their period of institutional delivery. Urinary cadmium concentrations were measured by inductively coupled plasma mass spectrometry. The real-time quantitative polymerase chain reaction detection was used to measure relative TL using genomic DNA isolated from umbilical cord blood leukocytes. Multivariate linear regression models were used to estimate the effect of prenatal urinary cadmium concentration on relative cord blood TL. RESULTS The geometric mean of maternal urinary cadmium concentration was 0.68 μg/g creatinine. In the multivariate-adjusted linear regression model, per doubling of maternal urinary cadmium concentration was associated with 6.83% (95% CI - 11.44%, - 1.97%; P = 0.006) shorter relative cord blood TL. Stratified analyses indicated that the inverse association between prenatal urinary cadmium and newborn relative TL was more pronounced among female infants and mothers < 29 years, while there were no significant effect modification according to infant sex (P for interaction = 0.907) and maternal age (P for interaction = 0.797). CONCLUSIONS The findings indicated that increased maternal urinary cadmium was associated with shortened relative cord blood TL. The results provide more evidence of the negative effects of environmental cadmium exposure and suggest that accelerated aging or cadmium-related diseases may begin in early life.
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Affiliation(s)
- Lina Zhang
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China
| | - Lulu Song
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China
| | - Bingqing Liu
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China
| | - Mingyang Wu
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China
| | - Lulin Wang
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China
| | - Bin Zhang
- Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Chao Xiong
- Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wei Xia
- Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China
| | - Yuanyuan Li
- Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China
| | - Zhongqiang Cao
- Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Youjie Wang
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China. .,Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China.
| | - Shunqing Xu
- Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China.
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22
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Yanuck SF. Microglial Phagocytosis of Neurons: Diminishing Neuronal Loss in Traumatic, Infectious, Inflammatory, and Autoimmune CNS Disorders. Front Psychiatry 2019; 10:712. [PMID: 31632307 PMCID: PMC6786049 DOI: 10.3389/fpsyt.2019.00712] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 09/05/2019] [Indexed: 01/08/2023] Open
Abstract
Errors in neuron-microglial interaction are known to lead to microglial phagocytosis of live neurons and excessive neuronal loss, potentially yielding poorer clinical outcomes. Factors that affect neuron-microglial interaction have the potential to influence the error rate. Clinical comorbidities that unfavorably impact neuron-microglial interaction may promote a higher rate of neuronal loss, to the detriment of patient outcome. This paper proposes that many common, clinically modifiable comorbidities have a common thread, in that they all influence neuron-microglial interactions. Comorbidities like traumatic brain injury, infection, stress, neuroinflammation, loss of neuronal metabolic integrity, poor growth factor status, and other factors, all have the potential to alter communication between neurons and microglia. When this occurs, microglial phagocytosis of live neurons can increase. In addition, microglia can shift into a morphological form in which they express major histocompatibility complex II (MHC-II), allowing them to function as antigen presenting cells that present neuronal debris as antigen to invading T cells. This can increase risk for the development of CNS autoimmunity, or can exacerbate existing CNS autoimmunity. The detrimental influence of these comorbidities has the potential to contribute to the mosaic of factors that determine patient outcome in some CNS pathologies that have neuropsychiatric involvement, including TBI and CNS disorders with autoimmune components, where excessive neuronal loss can yield poorer clinical outcomes. Recognition of the impact of these comorbidities may contribute to an understanding of the common clinical observation that many seemingly disparate factors contribute to the overall picture of case management and clinical outcome in these complex disorders. In a clinical setting, knowing how these comorbidities can influence neuron-microglial interaction can help focus surveillance and care on a broader group of potential therapeutic targets. Accordingly, an interest in the mechanisms underlying the influence of these factors on neuron-microglial interactions is appropriate. Neuron-microglial interaction is reviewed, and the various mechanisms by which these potential comorbidities influence neuro-microglial interaction are described.
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Affiliation(s)
- Samuel F Yanuck
- Program on Integrative Medicine, Department of Physical Medicine and Rehabilitation, University of North Carolina School of Medicine, Chapel Hill, NC, United States
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23
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Wai KM, Umezaki M, Kosaka S, Mar O, Umemura M, Fillman T, Watanabe C. Impact of prenatal heavy metal exposure on newborn leucocyte telomere length: A birth-cohort study. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2018; 243:1414-1421. [PMID: 30278415 DOI: 10.1016/j.envpol.2018.09.090] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 08/29/2018] [Accepted: 09/18/2018] [Indexed: 06/08/2023]
Abstract
Arsenic, cadmium and lead are toxic environmental contaminants. They were shown to be associated with telomere length (TL) in adults. Although they can cross the placental barrier, the effect of prenatal exposure of these metals on newborn TL is unknown. The aim of this study was to examine whether prenatal exposure to heavy metals has an impact on newborn leucocyte TL. A birth-cohort study was conducted with 409 pregnant women and their newborns in Myanmar. During the first visit, face-to-face interviews were conducted, and maternal spot urine sampling was performed. Cord blood samples were collected during follow-up. Urinary heavy metal concentration was measured by ICP-MS and adjusted for creatinine. Relative TL was measured by quantitative real-time polymerase chain reaction. The extent of prenatal arsenic, cadmium and lead exposure and their associations with newborn leucocyte TL were assessed using multivariate linear regression. The median values of maternal urinary arsenic, cadmium, and lead concentrations were 73.9, 0.9, and 1.8 μg/g creatinine, respectively. Prenatal arsenic and cadmium exposure was significantly associated with newborn TL shortening (lowest vs highest quartile, coefficient = - 0.13, 95% CI: - 0.22, - 0.03, p = 0.002, and coefficient = - 0.17, 95% CI: - 0.27, - 0.07, p = 0.001, respectively), and the associations remained robust after adjusting for confounders. There was no significant association between prenatal lead exposure and newborn TL. The present study identified the effect of arsenic and cadmium exposure on TL shortening, even in utero exposure at a lower concentration.
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Affiliation(s)
- Kyi Mar Wai
- Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, Japan.
| | - Masahiro Umezaki
- Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, Japan
| | - Satoko Kosaka
- Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, Japan
| | - Ohn Mar
- Department of Physiology, The University of Medicine (1), Yangon, Myanmar
| | - Mitsutoshi Umemura
- Hokkaido Research Center, Forestry and Forest Products Research Institute, Forest Research and Management Organization, Sapporo, Japan
| | - Toki Fillman
- Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, Japan
| | - Chiho Watanabe
- Department of Human Ecology, School of International Health, Graduate School of Medicine, The University of Tokyo, Japan; National Institute for Environmental Studies, Japan
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24
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Zhang J, Wang Y, Fu L, Wang B, Ji YL, Wang H, Xu DX. Chronic cadmium exposure induced hepatic cellular stress and inflammation in aged female mice. J Appl Toxicol 2018; 39:498-509. [PMID: 30375035 DOI: 10.1002/jat.3742] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 09/11/2018] [Accepted: 09/25/2018] [Indexed: 01/04/2023]
Abstract
Previous studies have revealed that acute cadmium (Cd) exposure led to inflammation in different organs through an oxidative stress mechanism. However, whether chronic Cd exposure induces inflammation in liver and the mechanistic link between inflammation and cell stress remains unclear. In the present study, we investigated the effects of chronic Cd exposure on hepatic cellular stress and inflammatory responses. Female CD1 mice were administrated with CdCl2 (10 and 100 mg/L) in drinking water for 57 weeks. Our results showed that the mRNA levels of Inos and the protein content of HO-1, markers of oxidative stress, were markedly increased in Cd-treated mice. In addition, the protein level of GRP78, the chaperone of endoplasmic reticulum (ER) stress, was significantly increased in Cd-treated mice. The expression of the proteins CHOP and peIF2α, two proteins downstream of ER stress, was also upregulated in the Cd-100 mg/L and Cd-10 mg/L group, respectively. Moreover, there were increased inflammatory cells existing in liver after Cd administration. Besides, there was a significant elevation in the mRNA level of Mip-2, Il-10 and Il-12 in the Cd-100 mg/L group. The mRNA level of Tgf-β was also upregulated in Cd-treated mice. Moreover, we also found that the number of Ki67-positive hepatic cells was increased in the Cd-10 mg/L group. Hence, our results indicated that chronic Cd exposure induced oxidative stress, ER stress, inflammatory responses and proliferation in the liver of aged female mice.
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Affiliation(s)
- Jun Zhang
- Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China.,Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.,Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, China
| | - Yan Wang
- Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China.,Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, China
| | - Lin Fu
- Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China.,Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.,Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, China
| | - Bo Wang
- Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China.,Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, China
| | - Yan-Li Ji
- Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China.,Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.,Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, China
| | - Hua Wang
- Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China.,Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.,Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, China
| | - De-Xiang Xu
- Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China.,Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, China.,Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, China
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25
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Zhao B, Vo HQ, Johnston FH, Negishi K. Air pollution and telomere length: a systematic review of 12,058 subjects. Cardiovasc Diagn Ther 2018; 8:480-492. [PMID: 30214863 DOI: 10.21037/cdt.2018.06.05] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Background Over recent decades, adverse effects of ambient air pollution on the cardiovascular system have been clearly demonstrated. However, the underlying mechanisms are not fully elucidated. Air pollution may accelerates biological aging and thereby the susceptibility to cardiovascular diseases (CVDs). Telomeres are tandem repetitive DNA complexes that play a critical role in maintaining chromosome stability. There are, however, heterogeneities among the reported effects of air pollution on telomere. This study sought to evaluate the existing literature on the association between air pollution and telomere length (TL). Methods Two reviewers independently searched on electronic databases including PUBMED, EMBASE, SCOPUS, WEB OF SCIENCE and Ovid. The key terms were "air pollution" and "telomere" without language restriction. Articles relating to tobacco smoke were excluded. Results A total of 12,058 subjects from 25 articles remained for final review. All were observational studies: 14 cross-sectional, 6 cohort and 5 case-control studies. Nineteen (76%) assessed leukocyte telomere length (LTL) of which 15 found associations between air pollution and shorter TL, 2 with longer TL, 1 had mixed results, and a study of patients with type 2 diabetes found non-significant associations with TL. One found longer TL from saliva. The remaining studies were of placental cells, buccal cells or sperm and all reported shorter TL associated with air pollution. Particulate matter (PM) was investigated in 8 articles, and the remainder assessed black carbon (BC), benzene, lead, cadmium and polycyclic aromatic hydrocarbon (PAH). Geographically, 11 studies were conducted in Europe, with 10 in Asia and 4 in North America. While all followed Cawthon's protocol for TL assessment, discordance in the reporting formats did not allow us to perform a quantitative meta-analysis. Conclusions Most of the studies support the association of shorter TL with air pollution. Uniform reporting format would be warranted for future studies to estimate true effect size of air pollution on TL.
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Affiliation(s)
- Bing Zhao
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - Ha Q Vo
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - Fay H Johnston
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - Kazuaki Negishi
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
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Tinkov AA, Filippini T, Ajsuvakova OP, Aaseth J, Gluhcheva YG, Ivanova JM, Bjørklund G, Skalnaya MG, Gatiatulina ER, Popova EV, Nemereshina ON, Vinceti M, Skalny AV. The role of cadmium in obesity and diabetes. THE SCIENCE OF THE TOTAL ENVIRONMENT 2017; 601-602:741-755. [PMID: 28577409 DOI: 10.1016/j.scitotenv.2017.05.224] [Citation(s) in RCA: 192] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Revised: 05/23/2017] [Accepted: 05/24/2017] [Indexed: 06/07/2023]
Abstract
Multiple studies have shown an association between environmental exposure to hazardous chemicals including toxic metals and obesity, diabetes, and metabolic syndrome. At the same time, the existing data on the impact of cadmium exposure on obesity and diabetes are contradictory. Therefore, the aim of the present work was to review the impact of cadmium exposure and status on the risk and potential etiologic mechanisms of obesity and diabetes. In addition, since an effect of cadmium exposure on incidence of diabetes mellitus and insulin resistance was suggested by several epidemiologic studies, we carried out a meta-analysis of all studies assessing risk of prevalence and incidence of diabetes. By comparing the highest versus the lowest cadmium exposure category, we found a high risk of diabetes incidence (odds ratio=1.38, 95% confidence interval 1.12-1.71), which was higher for studies using urine as exposure assessment. On the converse, results of epidemiologic studies linking cadmium exposure and overweight or obesity are far less consistent and even conflicting, also depending on differences in exposure levels and the specific marker of exposure (blood, urine, hair, nails). In turn, laboratory studies demonstrated that cadmium adversely affects adipose tissue physiopathology through several mechanisms, thus contributing to increased insulin resistance and enhancing diabetes. However, intimate biological mechanisms linking Cd exposure with obesity and diabetes are still to be adequately investigated.
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Affiliation(s)
- Alexey A Tinkov
- Yaroslavl State University, Yaroslavl, Russia; Orenburg State Medical University, Orenburg, Russia; RUDN University, Moscow, Russia.
| | - Tommaso Filippini
- CREAGEN, Environmental, Genetic and Nutritional Epidemiology Research Center, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Jan Aaseth
- Department of Public Health, Hedmark University of Applied Sciences, Elverum, Norway; Research Department, Innlandet Hospital Trust, Brumunddal, Norway
| | - Yordanka G Gluhcheva
- Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria
| | - Juliana M Ivanova
- Faculty of Medicine, Sofia University "St. Kliment Ohridski", Sofia, Bulgaria
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine, Mo i Rana, Norway
| | | | - Eugenia R Gatiatulina
- Orenburg State Medical University, Orenburg, Russia; South-Ural State Medical University, Chelyabinsk, Russia
| | - Elizaveta V Popova
- Orenburg State Medical University, Orenburg, Russia; St Joseph University in Tanzania, St Joseph College of Health Sciences, Dar es salaam, Tanzania
| | | | - Marco Vinceti
- CREAGEN, Environmental, Genetic and Nutritional Epidemiology Research Center, University of Modena and Reggio Emilia, Modena, Italy
| | - Anatoly V Skalny
- Yaroslavl State University, Yaroslavl, Russia; RUDN University, Moscow, Russia; Orenburg State Pedagogical University, Orenburg, Russia
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Health Risks Associated with Exposure to Filamentous Fungi. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2017; 14:ijerph14070719. [PMID: 28677641 PMCID: PMC5551157 DOI: 10.3390/ijerph14070719] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 06/19/2017] [Accepted: 06/23/2017] [Indexed: 01/06/2023]
Abstract
Filamentous fungi occur widely in the environment, contaminating soil, air, food and other substrates. Due to their wide distribution, they have medical and economic implications. Regardless of their use as a source of antibiotics, vitamins and raw materials for various industrially important chemicals, most fungi and filamentous fungi produce metabolites associated with a range of health risks, both in humans and in animals. The association of filamentous fungi and their metabolites to different negative health conditions in humans and animals, has contributed to the importance of investigating different health risks induced by this family of heterotrophs. This review aims to discuss health risks associated with commonly occurring filamentous fungal species which belong to genera Aspergillus, Penicillium and Fusarium, as well as evaluating their pathogenicity and mycotoxic properties.
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Phuagkhaopong S, Ospondpant D, Kasemsuk T, Sibmooh N, Soodvilai S, Power C, Vivithanaporn P. Cadmium-induced IL-6 and IL-8 expression and release from astrocytes are mediated by MAPK and NF-κB pathways. Neurotoxicology 2017; 60:82-91. [DOI: 10.1016/j.neuro.2017.03.001] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 03/04/2017] [Accepted: 03/06/2017] [Indexed: 11/24/2022]
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Nomura SJO, Robien K, Zota AR. Serum Folate, Vitamin B-12, Vitamin A, γ-Tocopherol, α-Tocopherol, and Carotenoids Do Not Modify Associations between Cadmium Exposure and Leukocyte Telomere Length in the General US Adult Population. J Nutr 2017; 147:538-548. [PMID: 28275103 PMCID: PMC5368581 DOI: 10.3945/jn.116.243162] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Revised: 11/21/2016] [Accepted: 02/06/2017] [Indexed: 01/10/2023] Open
Abstract
Background: Leukocyte telomere length (LTL) is a biomarker of the aging process and is associated with the risk of chronic disease. Higher exposure to cadmium may be associated with shorter LTL, and adequate nutrient concentrations may be associated with longer LTL; however, the potential interaction between metals and nutrients on LTL has yet to be examined.Objectives: The objective of this study was to evaluate whether serum concentrations of vitamins and carotenoids were associated with LTL, and whether they modified the association between blood cadmium and LTL in the US NHANES (1999-2002).Methods: We evaluated cross-sectional associations between LTL and serum concentrations of vitamin A, γ-tocopherol, α-tocopherol, folate, and vitamin B-12 (1999-2002; n = 7458) and α-carotene, β-carotene, β-cryptoxanthin, lutein + zeaxanthin, and lycopene (2001-2002; n = 4018) in a nationally representative sample of US adults (≥20 y of age) with the use of multivariable linear regression. We further investigated whether vitamin and carotenoid concentrations modified associations between blood cadmium and LTL with models stratified by serum nutrient concentrations and the inclusion of an interaction term.Results: Blood cadmium was inversely associated with LTL (percentage of LTL difference per 1 μg/L = -3.74; 95% CI: -5.35, -2.10). Serum vitamin A was positively associated (percentage of LTL difference per 1 μg/L = 4.01; 95% CI: 0.26, 7.90) and γ-tocopherol was inversely associated (percentage of LTL difference per 1 μg/dL = -2.49; 95% CI: -4.21, -0.73) with LTL. Serum folate (P-trend = 0.06) and α-tocopherol (P-trend = 0.10) were marginally positively associated with LTL, whereas vitamin B-12 (P-trend = 0.78) was not associated with LTL. Serum carotenoids were generally positively associated with LTL. Serum vitamin and carotenoid concentrations did not modify blood cadmium and LTL associations (P-interaction > 0.10).Conclusions: Results from this cross-sectional study suggest that exposure to cadmium and certain nutrients may be associated with LTL in US adults, but the serum concentrations of the vitamins and carotenoids evaluated did not modify cross-sectional associations between cadmium exposure and LTL.
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Affiliation(s)
- Sarah JO Nomura
- Office of Minority Health and Health Disparities Research, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC; and,To whom correspondence should be addressed. E-mail:
| | - Kim Robien
- Department of Exercise and Nutrition Sciences and
| | - Ami R Zota
- Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC
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Odewumi CO, Latinwo LM, Ruden ML, Badisa VLD, Fils-Aime S, Badisa RB. Modulation of cytokines and chemokines expression by NAC in cadmium chloride treated human lung cells. ENVIRONMENTAL TOXICOLOGY 2016; 31:1612-1619. [PMID: 26138014 PMCID: PMC4698366 DOI: 10.1002/tox.22165] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 06/01/2015] [Accepted: 06/07/2015] [Indexed: 05/28/2023]
Abstract
Cadmium (Cd), is one of the most hazardous metals found in the environment. Cd exposure through inhalation has been linked to various diseases in lungs. It was shown that Cd induces proinflammatory cytokines through oxidative stress mechanism. In this report, we studied the immunomodulatory effect of a well known antioxidant, N-acetylcysteine (NAC) on cadmium chloride (CdCl2 ) treated human lung A549 cells through human cytokine array 6. The lung cells were treated with 0 or 75 µM CdCl2 alone, 2.5 mM NAC alone, or co-treated with 2.5 mM NAC and 75 µM CdCl2 for 24 h. The viability of cells was measured by crystal violet dye. The array results were validated by human IL-1alpha enzyme- linked immunosorbent assay (ELISA) kit. The viability of the 75 µM CdCl2 alone treated cells was decreased to 44.5%, while the viability of the co-treated cells with 2.5 mM NAC was increased to 84.1% in comparison with untreated cells. In the cell lysate of CdCl2 alone treated cells, 19 and 8 cytokines were up and down-regulated, while in the medium 15 and 3 cytokines were up and downregulated in comparison with the untreated cells. In the co-treated cells, all these cytokines expression was modulated by the NAC treatment. The IL-1α ELISA result showed the same pattern of cytokine expression as the cytokine array. This study clearly showed the modulatory effect of NAC on cytokines and chemokines expression in CdCl2- treated cells and suggests the use of NAC as protective agent against cadmium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1612-1619, 2016.
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Affiliation(s)
- Caroline O Odewumi
- Department of Biological Sciences, College of Science and Technology, Florida A&M University, Tallahassee, Florida, USA.
| | - Lekan M Latinwo
- Department of Biological Sciences, College of Science and Technology, Florida A&M University, Tallahassee, Florida, USA
| | - Michael L Ruden
- Department of Biological Sciences, College of Science and Technology, Florida A&M University, Tallahassee, Florida, USA
| | - Veera L D Badisa
- Department of Biological Sciences, College of Science and Technology, Florida A&M University, Tallahassee, Florida, USA
| | - Sheila Fils-Aime
- Department of Biological Sciences, College of Science and Technology, Florida A&M University, Tallahassee, Florida, USA
| | - Ramesh B Badisa
- Department of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, USA
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Mortada WI, Nabieh KA, Donia AF, Ismail AM, Kenawy IMM. Impact of dialyzer membrane flux on metal clearance in hemodialysis patients. J Trace Elem Med Biol 2016; 36:52-6. [PMID: 27259352 DOI: 10.1016/j.jtemb.2016.04.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 04/04/2016] [Accepted: 04/06/2016] [Indexed: 11/16/2022]
Abstract
Deficiency of essential trace elements (such as Cu or Zn) and accumulation of potentially toxic trace elements (as Cd or Pb) are both known to have adverse effects in hemodialysis (HD) patients. Up to our knowledge, no studies about the permeability of low and high flux polysulfone membranes on metal ions during hemodialysis are available. Therefore, the aim of the present study was to address this issue. Forty one hemodialysis patients (19 were using high flux polysulfone membrane while the remaining were using low flux one) participated in the study. Blood levels of Cu, Zn, Cd and Pb were determined by graphite furnace atomic absorption spectrometry among HD patients, before and after dialysis session, as well as among matched 40 healthy persons. Blood concentrations of Cu and Zn in the whole hemodialysis group was significantly lower than those of the healthy control group, on the other hand the toxic metals (Cd and Pb) levels were observed to be significantly higher among HD patients compared to the normal persons. Among the hemodialysis group, there were no significant differences between the low and high flux dialyzer groups in terms of pre-dialysis blood levels of Cu, Zn, Cd and Pb. In addition, significantly decreased levels of all metal ions were observed after dialysis sessions using either low or high flux membranes. An exception was Pb which did not show any difference between pre-dialysis and post-dialysis values in the low flux groupIn conclusion Zn and Cu deficiencies should be considered in the treatment of these patients. High flux membranes are more efficient than low flux ones in removing excess Cd and Pb. Therefore, when high flux membranes are used, chelation therapy might not be required for Cd and Pb overload.
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Affiliation(s)
- Wael I Mortada
- Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt.
| | - Kareem A Nabieh
- Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt
| | - Ahmed F Donia
- Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt
| | - Amani M Ismail
- Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt
| | - Ibrahim M M Kenawy
- Chemistry Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt
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Acute exposure to cadmium induces prolonged neutrophilia along with delayed induction of granulocyte colony-stimulating factor in the livers of mice. Arch Toxicol 2016; 90:3005-3015. [DOI: 10.1007/s00204-016-1661-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Accepted: 01/04/2016] [Indexed: 10/22/2022]
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Abstract
The aim of this study was to investigate the toxic effect of the metal salt cadmium chloride dihydrate on the rabbit kidney cell line using the xCELLigence system or real-time cell analyser (RTCA), and to compare this relatively new method with standard biological cytotoxicity assays. This system provides real-time monitoring of cell behaviour and proliferative activity during the whole time of experiment. Moreover, after 24 h exposure of cells to cadmium, colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5-difenyl tetrazolium bromide (MTT) test was used to measure the metabolic activity and cytotoxicity was determined by measurement of lactate dehydrogenase (LDH) leaked from damaged cells. We found that renal cells exposed to lower concentrations (5–10 mg·l-1) of cadmium tend to grow similarly to control cells, however, cell index was significantly different (P < 0.05) after 24 h. With increasing concentration of cadmium (15–50 mg·l-1) significantly lower proliferative (P < 0.05) and metabolic activity (P < 0.05) of cells was observed and cytotoxicity increased simultaneously (P < 0.001). In addition, we found that the real-time monitoring of the cell response was significantly correlated with commonly used biological methods for toxicity measurement, for MTT assay R2 was 0.9448 (P < 0.01) and for LDH assay R2 was 0.9466 (P < 0.01), respectively. The present study is the first report when combination of RTCA, MTT assay and LDH test was used for cadmium nephrotoxicity assessment. In all these methods, the toxic effect of cadmium on rabbit kidney cells increased in a concentration-dependent manner.
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Song MK, Lee HS, Ryu JC. Integrated analysis of microRNA and mRNA expression profiles highlights aldehyde-induced inflammatory responses in cells relevant for lung toxicity. Toxicology 2015; 334:111-21. [DOI: 10.1016/j.tox.2015.06.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 06/08/2015] [Accepted: 06/09/2015] [Indexed: 12/12/2022]
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Choudhary AK, Sheela Devi R. Longer period of oral administration of aspartame on cytokine response in Wistar albino rats. ACTA ACUST UNITED AC 2015; 62:114-22. [DOI: 10.1016/j.endonu.2014.11.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Revised: 11/05/2014] [Accepted: 11/11/2014] [Indexed: 12/27/2022]
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Zota AR, Needham BL, Blackburn EH, Lin J, Park SK, Rehkopf DH, Epel ES. Associations of cadmium and lead exposure with leukocyte telomere length: findings from National Health and Nutrition Examination Survey, 1999-2002. Am J Epidemiol 2015; 181:127-36. [PMID: 25504027 DOI: 10.1093/aje/kwu293] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Cadmium and lead are ubiquitous environmental contaminants that might increase risks of cardiovascular disease and other aging-related diseases, but their relationships with leukocyte telomere length (LTL), a marker of cellular aging, are poorly understood. In experimental studies, they have been shown to induce telomere shortening, but no epidemiologic study to date has examined their associations with LTL in the general population. We examined associations of blood lead and cadmium (n = 6,796) and urine cadmium (n = 2,093) levels with LTL among a nationally representative sample of US adults from the National Health and Nutrition Examination Survey (1999-2002). The study population geometric mean concentrations were 1.67 µg/dL (95% confidence interval (CI): 1.63, 1.70) for blood lead, 0.44 µg/L (95% CI: 0.42, 0.47) for blood cadmium, and 0.28 µg/L (95% CI: 0.27, 0.30) for urine cadmium. After adjustment for potential confounders, the highest (versus lowest) quartiles of blood and urine cadmium were associated with -5.54% (95% CI: -8.70, -2.37) and -4.50% (95% CI: -8.79, -0.20) shorter LTLs, respectively, with evidence of dose-response relationship (P for trend < 0.05). There was no association between blood lead concentration and LTL. These findings provide further evidence of physiological impacts of cadmium at environmental levels and might provide insight into biological pathways underlying cadmium toxicity and chronic disease risks.
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N-acetyl-serotonin protects HepG2 cells from oxidative stress injury induced by hydrogen peroxide. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2014; 2014:310504. [PMID: 25013541 PMCID: PMC4074966 DOI: 10.1155/2014/310504] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2014] [Revised: 04/10/2014] [Accepted: 05/03/2014] [Indexed: 12/12/2022]
Abstract
Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2 produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity.
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Binker MG, Cosen-Binker LI. Acute pancreatitis: The stress factor. World J Gastroenterol 2014; 20:5801-5807. [PMID: 24914340 PMCID: PMC4024789 DOI: 10.3748/wjg.v20.i19.5801] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 03/12/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications. Etiologies of pancreatitis vary, with gallstones accounting for the majority of all cases, followed by alcohol. Other causes of pancreatitis include trauma, ischemia, mechanical obstruction, infections, autoimmune, hereditary, and drugs. The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion, intracellular activation of proteases, and generation of inflammatory mediators. Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells, whose systemic action ultimately determined the severity of the disease. Indeed, severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome, characterized by a progressive physiologic failure of several interdependent organ systems. Stress occurs when homeostasis is threatened, and stressors can include physical or mental forces, or combinations of both. Depending on the timing and duration, stress can result in beneficial or harmful consequences. While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis, the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention. This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis.
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Colacino JA, Arthur AE, Ferguson KK, Rozek LS. Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress. ENVIRONMENTAL RESEARCH 2014; 131:6-12. [PMID: 24607659 PMCID: PMC4057047 DOI: 10.1016/j.envres.2014.02.003] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Revised: 12/11/2013] [Accepted: 02/10/2014] [Indexed: 05/25/2023]
Abstract
Chronic cadmium exposure may cause disease through induction of systemic oxidative stress and inflammation. Factors that mitigate cadmium toxicity and could serve as interventions in exposed populations have not been well characterized. We used data from the 2003-2010 National Health and Nutrition Examination Survey to quantify diet׳s role in modifying associations between cadmium exposure and oxidative stress and inflammation. We created a composite antioxidant and anti-inflammatory diet score (ADS) by ranking participants by quintile of intake across a panel of 19 nutrients. We identified associations and effect modification between ADS, urinary cadmium, and markers of oxidative stress and inflammation by multiple linear regression. An interquartile range increase in urinary cadmium was associated with a 47.5%, 8.8%, and 3.7% increase in C-reactive protein (CRP), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP), respectively. An interquartile range increase in ADS was associated with an 7.4%, 3.3%, 5.2%, and 2.5% decrease in CRP, GGT, ALP, and total white blood cell count respectively, and a 3.0% increase in serum bilirubin. ADS significantly attenuated the association between cadmium exposure, CRP and ALP. Dietary interventions may provide a route to reduce the impact of cadmium toxicity on the population level.
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Affiliation(s)
- Justin A Colacino
- Department of Environmental Health Sciences, University of Michigan School of Public Health, 6630 SPH Tower, 1415 Washington Heights, Ann Arbor, MI 48109, USA
| | - Anna E Arthur
- Department of Environmental Health Sciences, University of Michigan School of Public Health, 6630 SPH Tower, 1415 Washington Heights, Ann Arbor, MI 48109, USA
| | - Kelly K Ferguson
- Department of Environmental Health Sciences, University of Michigan School of Public Health, 6630 SPH Tower, 1415 Washington Heights, Ann Arbor, MI 48109, USA
| | - Laura S Rozek
- Department of Environmental Health Sciences, University of Michigan School of Public Health, 6630 SPH Tower, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
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Involvement of oxidative stress and inflammation in liver injury caused by perfluorooctanoic acid exposure in mice. BIOMED RESEARCH INTERNATIONAL 2014; 2014:409837. [PMID: 24724082 PMCID: PMC3958804 DOI: 10.1155/2014/409837] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Accepted: 01/19/2014] [Indexed: 02/07/2023]
Abstract
Perfluorooctanoic acid (PFOA) is widely present in the environment and has been reported to induce hepatic toxicity in animals and humans. In this study, mice were orally administered different concentrations of PFOA (2.5, 5, or 10 mg/kg/day). Histological examination showed that the exposure to PFOA for 14 consecutive days led to serious hepatocellular injury and obvious inflammatory cell infiltration. In addition, malondialdehyde formation and hydrogen peroxide generation, indicators of oxidative stress, were significantly induced by PFOA treatment in the liver of mice. Furthermore, hepatic levels of interleukin-6, cyclooxygenase-2, and C-reactive protein, markers of inflammatory response, were markedly increased by exposure to PFOA in mice. These results demonstrated that PFOA-induced hepatic toxicity may be involved in oxidative stress and inflammatory response in mice.
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Holovska K, Almasiova V, Cigankova V. Ultrastructural changes in the rabbit liver induced by carbamate insecticide bendiocarb. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART. B, PESTICIDES, FOOD CONTAMINANTS, AND AGRICULTURAL WASTES 2014; 49:616-623. [PMID: 24901965 DOI: 10.1080/03601234.2014.911593] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Carbamates (CB) are used as insecticides and some of them have been registered as human drugs. The mechanism of CB poisoning involves reversible inhibition of acetylcholine esterase. In the present study, we investigated changes in liver ultrastructure in rabbits (Oryctolagus cuniculus) which were administered bendiocarb for 3, 10, 20, and 30 days. Rabbits in all experimental groups received capsules of bendiocarb (96% Bendiocarb, Bayer, Germany) per os daily at a dose of 5 mg/kg of body weight, and after day 11 received the same dose every 48 h. The observed changes were only moderate, focal, and the effect on the liver was not uniform. On the third day of the experiment, injured hepatocytes had dilated bile capillaries with reduced microvilli. There were no visible alterations in the intercellular contacts. Nuclei of these cells were irregular in shape. Many hepatocytes showed considerable increase in the number of peroxisomes. On day 10 of the experiment, the number of peroxisomes was reduced. Other changes, such as dilated rough endoplasmic reticulum and proliferation of smooth endoplasmic reticulum were observed on day 20. The number of lipid droplets in hepatocytes gradually increased. Usually they were present in low numbers, but on day 30 of the experiment their number increased significantly. They coalesced and formed a single lipid droplet which changed the shape of the nuclei. The results presented in this study indicate that both short and long-term administration of bendiocarb affects the liver ultrastructure. At the same time we also observed rapid onset of regeneration of the damaged tissue through activation of hepatocytes and oval cells.
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Affiliation(s)
- Katarina Holovska
- a Department of Anatomy, Histology and Physiology , University of Veterinary Medicine and Pharmacy , Kosice , Slovak Republic
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Zwolak I. Vanadium carcinogenic, immunotoxic and neurotoxic effects: a review ofin vitrostudies. Toxicol Mech Methods 2013; 24:1-12. [DOI: 10.3109/15376516.2013.843110] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Song MK, Lee HS, Choi HS, Shin CY, Kim YJ, Park YK, Ryu JC. Octanal-induced inflammatory responses in cells relevant for lung toxicity. Hum Exp Toxicol 2013; 33:710-21. [DOI: 10.1177/0960327113506722] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Inhalation is an important route of aldehyde exposure, and lung is one of the main targets of aldehyde toxicity. Octanal is distributed ubiquitously in the environment and is a component of indoor air pollutants. We investigated whether octanal exposure enhances the inflammatory response in the human respiratory system by increasing the expression and release of cytokines and chemokines. The effect of octanal in transcriptomic modulation was assessed in the human alveolar epithelial cell line A549 using oligonucleotide arrays. We identified a set of genes differentially expressed upon octanal exposure that may be useful for monitoring octanal pulmonary toxicity. These genes were classified according to the Gene Ontology functional category and Kyoto Encyclopedia of Genes and Genomes analysis to explore the biological processes related to octanal-induced pulmonary toxicity. The results show that octanal affects the expression of several chemokines and inflammatory cytokines and increases the levels of interleukin 6 (IL-6) and IL-8 released. In conclusion, octanal exposure modulates the expression of cytokines and chemokines important in the development of lung injury and disease. This suggests that inflammation contributes to octanal-induced lung damage and that the inflammatory genes expressed should be studied in detail, thereby laying the groundwork for future biomonitoring studies.
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Affiliation(s)
- M-K Song
- Center for Integrated Risk Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology, Cheongryang, Seoul, Korea
- School of Life Sciences and Biotechnology, Korea University, Anam-Dong, Seoungbuk-Gu, Seoul, Korea
| | - H-S Lee
- Center for Integrated Risk Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology, Cheongryang, Seoul, Korea
| | - H-S Choi
- Center for Integrated Risk Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology, Cheongryang, Seoul, Korea
| | - C-Y Shin
- Center for Integrated Risk Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology, Cheongryang, Seoul, Korea
| | - Y-J Kim
- Department of Marine Sciences, Incheon National University, Yeonsu-gu, Incheon, Korea
| | - Y-K Park
- School of Life Sciences and Biotechnology, Korea University, Anam-Dong, Seoungbuk-Gu, Seoul, Korea
| | - J-C Ryu
- Center for Integrated Risk Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology, Cheongryang, Seoul, Korea
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Kermanizadeh A, Gaiser BK, Ward MB, Stone V. Primary human hepatocytes versus hepatic cell line: assessing their suitability for in vitro nanotoxicology. Nanotoxicology 2012; 7:1255-71. [PMID: 23009365 DOI: 10.3109/17435390.2012.734341] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The use of hepatocyte cell lines as a replacement for animal models have been heavily criticised mainly due to low expression of metabolism enzymes. This study compares primary human hepatocytes with the C3A cell line and with respect to their response to a panel of nanomaterials (NMs; two ZnO, two MWCNTs, one Ag and one positively functionalised TiO₂). The cell line was very comparable with the primary hepatocytes with regards to their cytotoxic response to the NMs (Ag > uncoated ZnO > coated ZnO). The LC₅₀ was not attained in the presence of the MWCNTs and the TiO₂ NMs. All NMs significantly increased IL-8 production, with no change in levels of TNF-α and IL-6. Albumin production was measured as an indicator of hepatic function. The authors found no change in levels of albumin with the exception of the coated ZnO NM at the LC₅₀ concentration. NM uptake was similar for both the primary hepatocytes and C3A cells as investigated by TEM. Meanwhile, the authors confirmed greater levels of CYP450 activity in untreated primary cells. This study demonstrates that the C3A cell line is a good model for investigating NM-induced hepatocyte responses with respect to uptake, cytotoxicity, pro-inflammatory cytokine production and albumin production.
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Affiliation(s)
- Ali Kermanizadeh
- Heriot-Watt University, School of Life Sciences, John Muir Building , Edinburgh, EH14 4AS, UK
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Moon MK, Kim MJ, Jung IK, Koo YD, Ann HY, Lee KJ, Kim SH, Yoon YC, Cho BJ, Park KS, Jang HC, Park YJ. Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level. J Korean Med Sci 2012; 27:644-52. [PMID: 22690096 PMCID: PMC3369451 DOI: 10.3346/jkms.2012.27.6.644] [Citation(s) in RCA: 139] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Accepted: 03/13/2012] [Indexed: 11/20/2022] Open
Abstract
Bisphenol A (BPA) has been reported to possess hepatic toxicity. We investigated the hypothesis that BPA, below the no observed adverse effect level (NOAEL), can induce hepatic damage and mitochondrial dysfunction by increasing oxidative stress in the liver. Two doses of BPA, 0.05 and 1.2 mg/kg body weight/day, were administered intraperitoneally for 5 days to mice. Both treatments impaired the structure of the hepatic mitochondria, although oxygen consumption rate and expression of the respiratory complex decreased only at the higher dose. The hepatic levels of malondialdehyde (MDA), a naturally occurring product of lipid peroxidation, increased, while the expression of glutathione peroxidase 3 (GPx3) decreased, after BPA treatment. The expression levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) also increased. In HepG2 cells, 10 or 100 nM of BPA also decreased the oxygen consumption rate, ATP production, and the mitochondrial membrane potential. In conclusion, doses of BPA below the NOAEL induce mitochondrial dysfunction in the liver, and this is associated with an increase in oxidative stress and inflammation.
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Affiliation(s)
- Min Kyong Moon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Min Joo Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - In Kyung Jung
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Do Koo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hwa Young Ann
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kwan Jae Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Soon Hee Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yeo Cho Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Bong-Jun Cho
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kyong Soo Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hak C. Jang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Joo Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Kyriakou LG, Tzirogiannis KN, Demonakou MD, Kourentzi KT, Mykoniatis MG, Panoutsopoulos GI. Gadolinium chloride pretreatment ameliorates acute cadmium-induced hepatotoxicity. Toxicol Ind Health 2011; 29:624-32. [DOI: 10.1177/0748233711430971] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Cadmium is a known industrial and environmental pollutant. It causes hepatotoxicity upon acute administration. Features of cadmium-induced acute hepatoxicity encompass necrosis, apoptosis, peliosis and inflammatory infiltration. Gadolinium chloride (GdCl3) may prevent cadmium-induced hepatotoxicity by suppressing Kupffer cells. The effect of GdCl3 pretreatment on a model of acute cadmium-induced liver injury was investigated. Male Wistar rats 4–5 months old were injected intraperitoneally with normal saline followed by cadmium chloride (CdCl2; 6.5 mg/kg) or GdCl3 (10 mg/kg) followed by CdCl2 (6.5 mg/kg; groups I and II, respectively). Rats of both the groups were killed at 9, 12, 16, 24, 48 and 60 h after cadmium intoxication. Liver sections were analyzed for necrosis, apoptosis, peliosis and mitoses. Liver regeneration was also evaluated by tritiated thymidine incorporation into hepatic DNA. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also determined. Hepatic necrosis, hepatocyte and nonparenchymal cell apoptosis and macroscopic and microscopic types of peliosis hepatis were minimized by gadolinium pretreatment. Serum levels of AST and ALT were also greatly diminished in rats of group II. Tritiated thymidine incorporation into hepatic DNA was increased in gadolinium pretreatment rats. Kupffer cell activation was minimal in both the groups of rats. Gadolinium pretreatment attenuates acute cadmium-induced liver injury in young Wistar rats, with mechanisms other than Kupffer cell elimination.
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Affiliation(s)
- Loukas G Kyriakou
- Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece
| | | | - Maria D Demonakou
- Histopathology Laboratory, Sismanoglion G.D. Hospital, Marousi, Attiki, Greece
| | - Kalliopi T Kourentzi
- Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece
| | - Michael G Mykoniatis
- Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece
| | - Georgios I Panoutsopoulos
- Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece
- Department of Nursing, University of Peloponnese, Orthias Artemidos and Plateon, Sparta, Lakonia, Greece
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Cormet-Boyaka E, Jolivette K, Bonnegarde-Bernard A, Rennolds J, Hassan F, Mehta P, Tridandapani S, Webster-Marketon J, Boyaka PN. An NF-κB-independent and Erk1/2-dependent mechanism controls CXCL8/IL-8 responses of airway epithelial cells to cadmium. Toxicol Sci 2011; 125:418-29. [PMID: 22094458 DOI: 10.1093/toxsci/kfr310] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Airway epithelial cells in the lung are the first line of defense against pathogens and environmental pollutants. Inhalation of the environmental pollutant cadmium has been linked to the development of lung cancer and chronic obstructive pulmonary disease, which are diseases characterized by chronic inflammation. To address the role of airway epithelial cells in cadmium-induced lung inflammation, we investigated how cadmium regulates secretion of interleukin 8 (IL-8) by airway epithelial cells. We show that exposure of human airway epithelial cells to subtoxic doses of cadmium in vitro promotes a characteristic inflammatory cytokine response consisting of IL-8, but not IL-1β or tumor necrosis factor-alpha. We also found that intranasal delivery of cadmium increases lung levels of the murine IL-8 homologs macrophage inflammatory protein-2 and keracinocyte-derived chemokine and results in an influx of Gr1+ cells into the lung. We determined that inhibition of the nuclear factor-κB (NF-κB) pathway had no effect on cadmium-induced IL-8 secretion by human airway epithelial cells, suggesting that IL-8 production was mediated through an NF-κB-independent pathway. Mitogen-activated protein kinases (MAPKs) are often involved in proinflammatory signaling. Cadmium could activate the main MAPKs (i.e., p38, JNK, and Erk1/2) in human airway epithelial cells. However, only pharmacological inhibition of Erk1/2 pathway or knockdown of the expression of Erk1 and Erk2 using small interfering RNAs suppressed secretion of IL-8 induced by cadmium. Our findings identify cadmium as a potent activator of the proinflammatory cytokine IL-8 in lung epithelial cells and reveal for the first time the role of an NF-κB-independent but Erk1/2-dependent pathway in cadmium-induced lung inflammation.
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Affiliation(s)
- Estelle Cormet-Boyaka
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Dorothy M. Davis Heart and Lung Research Institute, Columbus, OH 43210, USA.
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Abstract
Context: This mini-review describes the toxic effects of vanadium pentoxide inhalation principally in the workplace and associated complications with breathing and respiration. Although there are some material safety data sheets available detailing the handling, hazards and toxicity of vanadium pentoxide, there are only two reviews listed in PubMed detailing its toxicity. Aim: To collate information on the consequences of occupational inhalation exposure of vanadium pentoxide on physiological function and wellbeing. Materials and Methods: The criteria used in the current mini-review for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability and Health. Articles were classified from an acute and chronic exposure and toxicity thrust. Results: The lungs are the principal route through which vanadium pentoxide enters the body. It can injure the lungs and bronchial airways possibly involving acute chemical pneumonotis, pulmonary edema and/or acute tracheobronchitis. It may adversely influence cardiac autonomic function. It stimulates the secretion of cytokines and chemokines by hepatocytes and disrupts mitochondria function. It disrupts the permeability of the epithelium and promotes access of inflammatory mediators to the underlying neuronal tissue causing injury and neuronal death. When renal brush border membrane vesicles are exposed to vanadium pentoxide, there is a time-dependent inhibition of citrate uptake and Na+ K+ ATPase in the membrane possibly contributing to nephrotoxicity. Exposure results in necrosis of spermatogonium, spermatocytes and Sertoli cells contributing to male infertility. Conclusion: Vanadium pentoxide certainly has adverse effects on the health and the well-being and measures need to be taken to prevent hazardous exposure of the like.
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Affiliation(s)
- Ross G Cooper
- Division of Physiology, UCE Birmingham, 701 Baker Building, Franchise Street, Perry Barr, Birmingham B42 2SU, UK
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Serum cadmium levels are independently associated with endothelial function in hemodialysis patients. Int Urol Nephrol 2011; 44:1487-92. [PMID: 21904850 DOI: 10.1007/s11255-011-0055-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2011] [Accepted: 08/23/2011] [Indexed: 10/17/2022]
Abstract
OBJECTIVE Hemodialysis (HD) patients are at risk of deficiency of essential trace elements and excess of toxic trace elements. The aim of the study was to evaluate the relation between the serum levels of some trace elements and heavy metals (iron, zinc, manganese, copper, magnesium, cobalt, cadmium, and lead) and endothelial function in HD patients. METHODS Forty-eight chronic HD patients without known atherosclerotic disease and 42 age- and sex-matched healthy individuals were included in the study. The serum levels of trace elements (iron, zinc, manganese, copper, and magnesium) and heavy metals (cobalt, cadmium, and lead) were measured by Atomic Adsorption Spectrophotometer (UNICAM-929). RESULTS The serum levels of iron, zinc, and manganese were lower, and levels of copper, magnesium, cobalt, cadmium, and lead were higher in HD patients compared to controls. Flow-mediated dilatation (FMD %) in HD patients was lower than that in the control group (7.27 ± 0.76 vs. 11.29 ± 0.82, P < 0.001). There was a significant negative correlation between FMD % and serum levels of cobalt (r = -0.313, P = 0.03) and cadmium (r = -0.524, P < 0.01). A linear regression analysis showed that serum cadmium levels were still significantly and negatively correlated with FMD % (regression coefficient = -0.526, P < 0.001). CONCLUSION We first demonstrated that serum cadmium levels independently predict endothelial function in HD patients without known atherosclerotic disease.
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Yen TH, Lin JL, Lin-Tan DT, Hsu CW, Chen KH, Hsu HH. Blood cadmium level's association with 18-month mortality in diabetic patients with maintenance haemodialysis. Nephrol Dial Transplant 2011; 26:998-1005. [PMID: 20667996 DOI: 10.1093/ndt/gfq448] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Cadmium exposure is related to severity of diabetes and diabetes-related organ damage in diabetic patients. Elevated blood cadmium levels (BCLs) are well known in maintenance haemodialysis (MHD) patients but the clinical significance in diabetic MHD patients remains unknown. METHODS A total of 212 diabetic MHD patients were enrolled in this 18-month prospective study and were categorized into three equal groups according to the basal BCL: high (> 0.889 μg/L; n = 71), middle (0.373-0.889 μg/L; n = 70) and low (< 0.373 μg/L; n = 71) BCL groups. The mortality and cause of death were recorded and analysed longitudinally. RESULTS Patients with high BCL had trends of higher white blood cell counts, glycosylated haemoglobin, phosphate and blood lead levels than other group patients. At the end of the follow-up, 31 patients had died. Kaplan-Meier analysis showed that the high BCL group patients had a higher mortality than other group patients (log-rank test, P = 0.036). Cox multivariate analysis demonstrated that logarithmic BCL was associated with increased hazard ratios (HR) for the all-cause mortality (HR = 2.336, 95% confidence intervals [CI] = 1.099-4.964, P = 0.027) in diabetic MHD patients. Similarly, if the low BCL group was the reference, the high BCL was associated with increased HR for all-cause mortality (HR = 2.865, 95% CI = 1.117-7.353, P = 0.043) in these patients. CONCLUSIONS The study results first demonstrated that BCL is associated with increased HR for 18-month all-cause mortality in diabetic MHD patients. Avoiding smoking and high cadmium-containing food may be important in these patients.
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Affiliation(s)
- Tzung-Hai Yen
- Department of Nephrology, Division of Clinical Toxicology, Chang Gung Memorial Hospital, Taipei, Lin-Kou Medical Center, Taoyuan, Chang Gung University and School of Medicine, Taipei, Taiwan, ROC
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