title: Mitochondrial dysfunction induced by Bisphenol A is a factor of its hepatotoxicity in rats.
abstract: Bisphenol A (BPA), an estrogenic and endocrine disrupting agent, is widely used in manufacturing of polycarbonate plastics and epoxy resins. BPA and other endocrine disrupting chemicals (EDCs) act via multiple mechanisms including interference with mitochondrial functions. Mitochondria are the hub of cellular energy pool and hence are the target of many EDCs. We studied perturbation of activities of mitochondrial enzymes by BPA and its possible role in hepatotoxicity in Wistar rats. Rats were exposed to BPA (150 mg/kg, 250 mg/kg, 500 mg/kg per os, for 14 days) and activities of enzymes of mitochondrial electron transport chain (ETC) were measured. Besides, other biochemical parameters such as superoxide generation, protein oxidation, and lipid peroxidation (LPO) were also measured. Our results indicated a significant decrease in the activities of enzymes of mitochondrial ETC complexes, i.e., complex I, II, III, IV, and V along with significant increase in LPO and protein oxidation. Additionally, a significant increase in mitochondrial superoxide generation was also observed. All these findings could be attributed to enhanced oxidative stress, decrease in reduced glutathione level, and decrease in the activity of superoxide dismutase in rat liver mitochondria isolated from BPA-treated rats. BPA treatment also caused a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase indicating its potential hepatotoxicity. Furthermore, histopathological findings revealed marked edema formation, hepatocellular degeneration, and necrosis of liver tissue in BPA-exposed rats. In conclusion, this study provides an evidence of impaired mitochondrial bioenergetics and liver toxicity after high-dose BPA exposure in rats. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1922-1934, 2016.
authors.affiliation: Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India.
authors.forename: Somaira
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India.
authors.forename: Saba
authors.initials: S
authors.lastname: Beigh
authors.affiliation: Central Pathology Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow, 226 001, India.
authors.forename: Bhushan P
authors.initials: BP
authors.lastname: Chaudhari
authors.affiliation: Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India.
authors.forename: Sayed
authors.initials: S
authors.lastname: Aliul Hasan Abdi
authors.affiliation: Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India.
authors.forename: Shahzad
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India.
authors.forename: Firoz
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India.
authors.forename: Suhel
authors.initials: S
authors.lastname: Parvez
authors.affiliation: Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India.
authors.forename: Sheikh
authors.initials: S
authors.lastname: Raisuddin
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D042967:Electron Transport Complex I / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D010636:Phenols / Q000633:toxicity*; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D042967:Electron Transport Complex I; D052244:Endocrine Disruptors; D005978:Glutathione; D010636:Phenols; D013482:Superoxide Dismutase; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: endocrine disrupting chemicals; hepatotoxicity; mitochondrial electron transport chain; oxidative stress