Importance of peroxisome proliferator-activated receptor-γ in hepatic ischemia/reperfusion injury in mice

Background/Aims: Peroxisome proliferator-activated receptor-gamma (PPARy) is a transcriptional factor belonging to the nuclear receptor superfamily. Recent studies have suggested that PPARy regulates inflammatory responses and PPARy specific agonists have beneficial effects on several disease conditions in the various organs. However, the precise role of PPAR gamma in acute liver injury remains unknown. Methods: We investigated the pathophysiological role of PPAR gamma and the effect of the selective PPARy agonist, pioglitazone, on the hepatic ischemia/reperfusion (I/R) injury. Results: PPARy expression in the liver was upregulated after reperfusion following ischemia. Pioglitazone treatment significantly inhibited hepatic I/R injury as determined by serological and histological analyses. The protective effect was associated with downregulation of the local expression of several potent proinflammatory cytokines, chemokines and adhesion molecules after reperfusion. The neutrophil accumulation was also inhibited by the treatment. Furthermore, the treatment inhibited the induction of apoptosis on hepatocytes. Finally, pioglitazone significantly improved the mouse survival in a lethal model of hepatic I/R injury. Conclusions: PPAR gamma plays an inhibitory role in hepatic I/R injury and the stimulation by selective agonist has a significant beneficial effect. Thus, PPAR gamma may be a new therapeutic target for the protection of the liver against acute injury. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.