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

被引：97

作者：

Liu, Qian ^{[1
,2
,3
]}

Wang, Qihan ^{[4
]}

Xu, Cheng ^{[2
,3
]}

Shao, Wentao ^{[2
,3
]}

Zhang, Chunlan ^{[2
,3
]}

Liu, Hui ^{[2
,3
]}

Jiang, Zhaoyan ^{[1
]}

Gu, Aihua ^{[2
,3
]}

机构：

[1] Tongji Univ, Shanghai East Hosp, Ctr Gallbladder Dis, Sch Med,Inst Gallstone Dis, Shanghai 201200, Peoples R China

[2] Nanjing Med Univ, Inst Toxicol, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Sch Publ Hlth, Key Lab Modern Toxicol, Minist Educ, Nanjing, Jiangsu, Peoples R China

[4] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Shanghai Inst Digest Surg,Dept Surg, Shanghai 200025, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

中国国家自然科学基金;

关键词：

PERSISTENT ORGANIC POLLUTANTS; POLYCHLORINATED-BIPHENYLS; SERUM CONCENTRATIONS; AGRICULTURAL SOILS; INSULIN-RESISTANCE; CHIRAL SIGNATURES; LIPID-METABOLISM; HUMAN TISSUES; EXPOSURE; RESIDUES;

D O I：

10.1038/srep46339

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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

引用

页数：11

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