Disruption of peroxisome proliferator-activated receptor α in hepatocytes protects against acetaminophen-induced liver injury by activating the IL-6/STAT3 pathway
Zhenzhen Zhang, Tiantian Yao, Nan Zhao, Hui Liu, Hao Cheng, Frank J. Gonzalez, Hua Wang, Guiqiang Wang, Aijuan Qu, Yan Wang
Abstract
Background & Aims: Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor abundantly expressed in liver. PPAR activator has been previously reported to protect against acetaminophen-induced hepatotoxicity, but fenofibrate, a lipid-lowering drug that activates PPAR, has a common side-effect causing liver injury. Thus, the exact effect of liver PPAR on drug-induced liver injury remains obscure. Methods: Hepatocyte-specific Ppara knockout mice and littermate wild-type control mice were intraperitoneally injected with acetaminophen (400 mg/kg body weight). Blood and liver samples were collected at different time points. We measured phase I and II cytochrome P450 enzymes, glutathione, reactive oxygen species, cytokines including Il6, and pSTAT3 by reverse transcriptase quantitative PCR, colorimetric, immunohistochemistry analyses and Western blotting.