title: Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism.
abstract: p,p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and β-hexachlorocyclohexane (β-HCH) were two predominant organochlorine pesticides (OCPs) metabolites in human body associated with disorders of fatty acid metabolism. However, the underlying mechanisms have not been fully clarified. In this study, adult male C57BL/6 mice were exposed to low dose of p, p'-DDE and β-HCH for 8 wk. OCPs accumulation in organs, hepatic fatty acid composition, tricarboxylic acid cycle (TCA) metabolites and other metabolite profiles were analyzed. Expression levels of genes involved in hepatic lipogenesis and β-oxidation were measured. Mitochondrial function was evaluated in HepG2 cells exposed to OCPs. High accumulation of p, p'-DDE and β-HCH was found in liver and damaged mitochondria was observed under electron microscopy. Expression of genes in fatty acid synthesis increased and that in mitochondrial fatty acid β-oxidation decreased in OCPs treatment groups. OCPs changed metabolite profiles in liver tissues, varied hepatic fatty acid compositions and levels of several TCA cycle metabolites. Furthermore, MitoTracker Green fluorescence, ATP levels, mitochondrial membrane potential and OCR decreased in HepG2 cells exposed to OCPs. In conclusion, chronic exposure to OCPs at doses equivalent to internal exposures in humans impaired mitochondrial function, decreased fatty acid β-oxidation and aggravated disorders of fatty acid metabolism.
authors.affiliation: Center of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of Medicine, Shanghai, 201200, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Shao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Chunlan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Center of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of Medicine, Shanghai, 201200, China.
authors.forename: Zhaoyan
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gu
mesh_terms: D000818:Animals; D002952:Citric Acid Cycle / Q000187:drug effects; D018450:Disease Progression; D005227:Fatty Acids / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D001556:Hexachlorocyclohexane / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D052439:Lipid Metabolism Disorders / Q000209:etiology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010575:Pesticides / Q000494:pharmacology*
chemical_list: D005227:Fatty Acids; D006843:Hydrocarbons, Chlorinated; D010575:Pesticides; D001556:Hexachlorocyclohexane; C023888:beta-hexachlorocyclohexane