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It was previously shown that acute pretreatment with simvastatin (1 mg/kg) significantly protects rats from renal ischemia-reperfusion injury (I/R, 45 min + 4 h). The aim of our present study was to determine whether this beneficial effect of simvastatin was dose-related. A single dose of simvastatin of 1 or 3 mg/kg, i.v. bolus, dissolved in 10% DMSO (Sim1 and Sim3), was injected 30 min before ischemia, 30 min before reperfusion or 5 min before reperfusion (30I, 30R, and 5R, respectively). Simvastatin-treated rats were compared to the appropriate controls (I/R + DMSO and Sham + DMSO group). Sim1 and Sim3 groups were similar regarding serum concentrations of urea, creatinine, aspartate aminotransferase, and gamma-glutamiltransferase (sUr, sCre, ALT, and γGT, respectively), as well as total histological score. Both doses of the drug (Sim1 and Sim3) were more effective in the reduction of total histological score in comparison with I/R + DMSO group. Also, the higher dose of drug 3 mg/kg (Sim3) was somewhat more effective than Sim1 in the reduction of tubular necrosis score and loss of brush border. In conclusion, the acute protective effect of simvastatin in the experimental model of renal I/R injury does not seem to be dose-related, and the dose of 1 mg/kg should be chosen for further investigation

Acute protective effects of different doses of simvastatin in the rat model of renal ischemia-reperfusion injury