Pyrazinamide induced hepatic injury in rats through inhibiting the PPARα pathway

Pyrazinamide (PZA) causes serious hepatotoxicity, but little is known about the exact mechanism by which PZA induced liver injury. The peroxisome proliferator-activated receptors alpha (PPAR) is highly expressed in the liver and modulates the intracellular lipidmetabolism. So far, the role of PPAR in the hepatotoxicity of PZA is unknown. In the present study, we described the hepatotoxic effects of PZA and the role of PPAR and its target genes in the downstream pathway including L-Fabp, Lpl, Cpt-1b, Acaa1, Apo-A1 and Me1 in this process. We found PZA induced the liver lipid metabolism disorder and PPAR expressionwas down-regulated which had a significant inverse correlation with liver injury degree. These changeswere ameliorated by fenofibrate, the co-treatment that acts as a PPAR agonist. In contrast, short-termstarvation significantly aggravated the severity of PZA-induced liver injury. In conclusion, this study demonstrated the critical role played by PPAR in PZA-induced hepatotoxicity and provided a better understanding of the molecular mechanisms underlying PZA-induced liver injury. Copyright (c) 2016 John Wiley & Sons, Ltd. In the present study, we described the hepatotoxic effects of PZA and the role of PPAR and its target genes in the downstream pathway including L-Fabp, Lpl, Cpt-1b, Acaa1, Apo-A1 and Me1 in this process. We found PZA induced the liver lipid metabolismdisorder and PPAR expression was down-regulated which had a significant inverse correlation with liver injury degree.