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.
journal_name
Chemospherejournal_title
Chemosphereauthors
Xiang D,Chu T,Li M,Wang Q,Zhu Gdoi
10.1016/j.chemosphere.2018.03.009subject
Has Abstractpub_date
2018-06-01 00:00:00pages
840-849eissn
0045-6535issn
1879-1298pii
S0045-6535(18)30413-2journal_volume
201pub_type
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