Protective effects of pioglitazone on renal ischemia-reperfusion injury in mice

Background: Renal ischemia-reperfusion injury (IRI) is a complex pathophysiologic process involving cell apoptosis and oxidant damages that leads to acute renal failure in both native kidneys and renal allografts. Pioglitazone is a novel class of oral antidiabetic agents currently used to treat type 2 diabetes mellitus. Pioglitazone exerts protective effects on acute myocardial ischemia and acute cerebral ischemia. The aim of this study was to investigate the possible beneficial effects of pioglitazone on renal IRI in mice. Methods: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. Fifty-five healthy male Balb/c mice were randomly assigned to one of the following groups: PBS + IRI, pioglitazone + IRI, PBS + sham IRI, pioglitazone + sham IRI. Kidney function tests, histopathologic examination, renal cell Bcl-2, and Bax expression were determined 24 h after reperfusion. Animals' survival was examined 7 days after operation. Results: Animals pretreated with pioglitazone had lower plasma levels of blood urea nitrogen and creatinine caused by IRI, lower histopathologic scores, and improved survival rates following IRI. Renal cell apoptosis induced by IRI was abrogated in kidneys of mice pretreated by pioglitazone, with an increase in Bcl-2 expression and a decrease in Bax expression. Furthermore, pioglitazone pretreatment protected against lethal renal IRI. Conclusions: Peroxisome proliferator-activated receptor activation by pioglitazone exerts protective effects on renal IRI in mice by abrogating renal cell apoptosis. Thus, pioglitazone could be a novel therapeutic tool in renal IRI. (C) 2012 Elsevier Inc. All rights reserved.