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Background: Renal ischemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allograft. This study aimed at investigating the effects ofmesenchymal stem cells (MSC) on ischemia/reperfusion (I/R) injury and the underlying mechanisms in a rat model. Methods: Renal ischemia was produced by clamping the right renal vessels for 60 min after the left kidney was removed. Immediately after visual confirmation of reflow, 1 × 106 MSC were administered by intravenous injection, followed by reperfusion for 24 h. The kidney functions, tissue malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were evaluated. Histopathological examinations were also performed. Results: MSC infusion significantly improved kidney function as indicated by lower urea and creatinine levels in the MSC compared to the vehicle group (p < 0.05). I/R-induced reduction in renal tissue SOD enzyme activity and GSH-Px was significantly improved by MSC (p < 0.05). Treatment with MSC also resulted in significant reduction in renal tissue MDA levels that were increased by renal I/R injury (p < 0.05). At histological examination, the kidneys of MSC-treated rats showed a fairly normal morphology. Conclusions: MSC protects the kidneys against I/R injury at least via their antioxidant effects. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]