当前位置： SCI文献检索 > ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY期刊下所有文献 > Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor α (PPARα).

Short-chain chlorinated paraffins (SCCPs) disrupt hepatic fatty acid metabolism in liver of male rat via interacting with peroxisome proliferator-activated receptor α (PPARα).

Abstract：

:Short-chain chlorinated paraffins (SCCPs) are frequently detected in environmental matrices and human tissues. It was hypothesized that SCCPs might interact with the peroxisome proliferator-activated receptor α (PPARα). In the present study, an in vitro, dual-luciferase reporter gene assay and in silico molecular docking analysis were employed together to study the interactions between SCCPs congeners and PPARα. Expressions of genes downstream in pathways activated by PPARα in liver of rats exposed to 1, 10, or 100 mg/kg bm/d of C10-13-CPs (56.5% Cl) for 28 days were examined to confirm activation potencies of SCCPs toward PPARα signaling. Effects of exposure to C10-13-CPs (56.5% Cl) on fatty acid metabolism in rat liver were also explored via a pseudo-targeted metabolomics strategy. Our results showed that C10-13-CPs (56.5% Cl) caused a dose-dependent greater expression of luciferase activity of rat PPARα. Molecular docking modeling revealed that SCCPs had a strong capacity to bind with PPARα only through hydrophobic interactions and the binding affinity was dependent on the degree of chlorination in SCCPs congeners. In livers of male rats, exposure to 100 mg/kg bm/d of C10-13-CPs (56.5% Cl) resulted in up-regulated expressions of 11 genes that are downstream in the PPARα-activated pathway and regulate catabolism of fatty acid. Consistently, accelerated fatty acid oxidation was observed mainly characterized by lesser concentrations of ∑fatty acids in livers of rats. Overall, these results demonstrated, for the first time, that SCCPs could activate rat PPARα signaling and thereby disrupt metabolism of fatty acid in livers of male rats.

journal_name

Ecotoxicol Environ Saf

journal_title

Ecotoxicology and environmental safety

authors

Gong Y,Zhang H,Geng N,Ren X,Giesy JP,Luo Y,Xing L,Wu P,Yu Z,Chen J

doi

10.1016/j.ecoenv.2019.06.003

subject

Has Abstract

pub_date

2019-10-15 00:00:00

pages

164-171

eissn

0147-6513

issn

1090-2414

pii

S0147-6513(19)30631-1

journal_volume

181

pub_type

杂志文章

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