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Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism.

ABSTRACT: p,p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and ?-hexachlorocyclohexane (?-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 ?-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 ?-oxidation were measured. Mitochondrial function was evaluated in HepG2 cells exposed to OCPs. High accumulation of p, p'-DDE and ?-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 ?-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 ?-oxidation and aggravated disorders of fatty acid metabolism.

SUBMITTER: Liu Q

PROVIDER: S-EPMC5387717 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism.

Liu Qian Q Wang Qihan Q Xu Cheng C Shao Wentao W Zhang Chunlan C Liu Hui H Jiang Zhaoyan Z Gu Aihua A

Scientific reports 20170411

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 metab ...[more]

PMID: 28397872

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Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism.

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Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism.

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