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Dual action of peroxisome proliferator-activated receptor alpha in perfluorodecanoic acid-induced hepatotoxicity.


ABSTRACT: Perfluorodecanoic acid (PFDA) is widely used in production of many daily necessities based on their surface properties and stability. It was assigned as a Persistent Organic Pollutant in 2009 and became a public concern partly because of its potential for activation of the peroxisome proliferator-activated receptor alpha (PPAR?). In this study, wild-type and Ppara-null mice were administered PFDA (80 mg/kg). Blood and liver tissues were collected and subjected to systemic toxicological and mechanistic analysis. UPLC-ESI-QTOFMS-based metabolomics was used to explore the contributing components of the serum metabolome that led to variation between wild-type and Ppar?-null mice. Bile acid homeostasis was disrupted, and slight hepatocyte injury in wild-type mice accompanied by adaptive regulation of bile acid synthesis and transport was observed. The serum metabolome in wild-type clustered differently from that in Ppar?-null, featured by sharp increases in bile acid components. Differential toxicokinetic tendency was supported by regulation of UDP-glucuronosyltransferases dependent on PPAR?, but it did not contribute to the hepatotoxic responses. Increase in Il-10 and activation of the JNK pathway indicated inflammation was induced by disruption of bile acid homeostasis in wild-type mice. Inhibition of p-p65 dependent on PPAR? activation by PFDA stopped the inflammatory cascade, as indicated by negative response of Il-6, Tnf-?, and STAT3 signaling. These data suggest disruptive and protective role of PPAR? in hepatic responses induced by PFDA.

SUBMITTER: Luo M 

PROVIDER: S-EPMC6350782 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Dual action of peroxisome proliferator-activated receptor alpha in perfluorodecanoic acid-induced hepatotoxicity.

Luo Min M   Tan Zhen Z   Dai Manyun M   Song Danjun D   Lin Jiao J   Xie Minzhu M   Yang Julin J   Sun Lu L   Wei Dengming D   Zhao Jinshun J   Gonzalez Frank J FJ   Liu Aiming A  

Archives of toxicology 20160625 2


Perfluorodecanoic acid (PFDA) is widely used in production of many daily necessities based on their surface properties and stability. It was assigned as a Persistent Organic Pollutant in 2009 and became a public concern partly because of its potential for activation of the peroxisome proliferator-activated receptor alpha (PPARα). In this study, wild-type and Ppara-null mice were administered PFDA (80 mg/kg). Blood and liver tissues were collected and subjected to systemic toxicological and mecha  ...[more]

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