Antioxidant activity of simvastatin prevents ifosfamide-induced nephrotoxicity

Ifosfamide is an anticancer agent used largely in treatment of solid tumors. The mainstay dose-limiting toxicity of ifosfamide is nephrotoxicity. This is largely believde to be a result of ifosfamide-induced oxidative stress. In this study, we investigated the antioxidant activity of simvastatin and the possible protective role of simvastatin against ifosfamide induced nephrotoxicity. Thirty Sprague-Dawely rats were divided into five groups and given orally different drug combinations. Group I and II were regarded as control groups and received 0.1% DMSO and normal saline, respectively. Group III received ifosfamide at 50 mg/kg, group IV received simvastatin at 0.3 mg/kg and group V received both ifosfamide and simvastatin. All animals were decapitated 2 days after the last ifosfamide administration. Findings revealed that ifosfamide induced nephrotoxicity as indicated by a significant increase in plasma creatinine and lipid per oxidation. This increase was significantly inhibited in animals pretreated with simvastatin. Histopathological observations were in correlation with the biochemical parameters in that simvastatin minimized ifosfamide-induced renal tubular damage. The above results promote a future use of simvastatin in combination with ifosfamide in treatment of cancer patients to indicate that simvastatin protectics against ifosfamide-induced nephrotoxicity in terms of oxidative stress and might be given in combination.