Paradoxical Effects of Atorvastatin on Renal Tubular Cells: An Experimental Investigation

Abstract

Introduction. Atorvastatin has antioxidant activity and has been reported to increase blood antioxidant capacity. This study aimed to evaluate the effect of different doses of atorvastatin on gentamicin-induced kidney injury.

Materials and Methods. In this experimental study, 30 male Wistar rats were designated into 6 equal groups for a 7-day period of intraperitoneal injections of gentamicin and atorvastatin. Group 1 received gentamicin, 80 mg/kg. Group 2 received phosphate buffer as the vehicle of atorvastatin. All rats in groups 3, 4, and 5 received gentamicin, 80 mg/kg/d, and then, after a 1-hour interval, atorvastatin was injected for 7 days as follow: group 3, 10 mg/kg/d; group 4, 50 mg/kg/d; and group 5, 150 mg/kg/d. Rats in group 6 received only 150 mg of atorvastatin. On the 8th day, blood samples were collected for evaluation of creatinine and blood urea nitrogen levels, and the animals' kidneys were dissected out for histopathological examinations.

Results. Morphological damages to the tubular cells in groups 3 and 4 were less than those in groups 1 and 5. Injuries to the renal tubular cells in the rats of group 5 (gentamicin and atorvastatin, 150 mg/kg/d) and in group 6 (atorvastatin 150 mg/kg/d alone) were more extensive than those in group 1.

Conclusions. The none-dose-dependent effect of atorvastatin in inducing renal tubular cell protection and renal tubular toxicity of atorvastatin in higher dose suggest administration of low-dose atorvastatin in critical conditions associated with renal tubular cell protection.