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Chemosphere. 2018 Jun;201:840-849. doi: 10.1016/j.chemosphere.2018.03.009. Epub 2018 Mar 3.

Effects of pyrethroid pesticide cis-bifenthrin on lipogenesis in hepatic cell line.

Author information

1
Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou 310058, PR China.
2
Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou 310058, PR China. Electronic address: wqiangwei@zju.edu.cn.

Abstract

Mounting evidence suggests there is a link between exposure to synthetic pyrethroids (SPs) and the development of obesity. The information presented in this study suggests that cis-bifenthrin (cis-BF) could activate pregnane X receptor (PXR) mediated pathway and lead to the lipid accumulation of human hepatoma (HepG2) cells. Cells were incubated in the control or different concentrations of cis-BF for 24 h. The 1 × 10-7 M and 1 × 10-6 M cis-BF exposure were found to induce cellular triglyceride (TG) accumulation significantly. This phenomenon was further supported by Oil Red O Staining assay. The cis-BF exposure caused upregulation of PXR gene and protein. Correspondingly, we also observed the increased expression of downstream genes involved in lipid formation and the inhibition of the expression of β-oxidation. As chiral pesticide,cis-BF was further conformed to behave enantioselectivity in the lipid metabolism. Rather than 1R-cis-BF, HepG2 cells incubated with 1S-cis-BF exhibited a significant TG accumulation. 1S-cis-BF also showed a higher binding level, of which the KD value was 9.184 × 10-8 M in the SPR assay, compared with 1R-cis-BF (3.463 × 10-6 M). In addition, the molecular docking simulation analyses correlated well with the KD values measured by the SPR, indicating that 1S-cis-BF showed a better binding affinity with PXR. The results in this study also elucidates the differences between the two enantiomers of pyrethroid-induced toxicity in lipid metabolism of non-target organism.

KEYWORDS:

Enantioselective; Lipid metabolism; Pregnane X receptor; Pyrethroids; cis-bifenthrin

[Indexed for MEDLINE]

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