Received for publication September 17, 2008.
Revised November 6, 2008.
Accepted for publication November 6, 2008.

Peroxisome-proliferator activated receptor- contributes to the resolution of inflammation following renal ischemia/reperfusion injury

Abstract

This study was designed to elucidate the role of peroxisome-proliferator activated receptor (PPAR)- in the development of inflammation following ischemia/reperfusion injury of the kidney. We have evaluated the effects of ischemia/reperfusion on renal dysfunction, injury and inflammation in wild-type mice or mice in which the gene for PPAR- has been deleted (PPAR-^-/-), and then treated with the PPAR- agonist fenofibrate. Mice were subjected to bilateral renal ischemia (30 min) and reperfusion (24 h), and received fenofibrate (3 mg/kg, i.p.) prior to reperfusion. Plasma creatinine, urea and aspartate aminotransferase were all used as indicators of renal dysfunction and injury. Kidneys were used for histological and immunohistochemical analysis, and markers of inflammation. Fenofibrate significantly attenuated the degree of renal dysfunction, injury and inflammation caused by ischemia/reperfusion injury. The degree of renal dysfunction, injury and inflammation caused by ischemia/reperfusion was also significantly augmented in PPAR-^-/- mice when compared to their wild-type littermates. Interestingly, fenofibrate did not protect PPAR-^-/- mice against ischemia/reperfusion injury. We, therefore, propose that ligands of PPAR- may be useful in the treatment of renal ischemia/reperfusion injury, and that endogenous PPAR- limits the degree of renal dysfunction, injury and inflammation associated with ischemia/reperfusion injury.

Key words: fenofibrate, inflammation, ischemia/reperfusion, mice, peroxisome-proliferator activated receptor alpha, renal