Effect of silymarin on cisplatin induced nephrotoxicity in normal rats

Cisplatin is one of the most widely used and effective chemotherapeutic drugs ever discovered against a variety of solid tumors. The aim of the present study was to analyze the effect of the flavonoid silymarin, a free radical scavenger that prevents lipoperoxidation, on nephrotoxicity induced by cisplatin in rat. Male albino rats were divided into five groups, 10 rats in each. The first group received a daily I.P. injection of normal saline [0.5 m1/150 gm body weight] for 5 consecutive days and served as saline-control group. In the second group, rats were injected I.P. with of 0.2 ml of propylene glycol in saline 75/25 v/v for 5 consecutive days and served as propylene glycol-control group. The third group were injected with a single dose of cisplatin [5 mg/kg, I.P.], whereas animals in the fourth group were injected with Silymarin [100 mg/kg/day for 5 consecutive days, I.P. injection] [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The Fifth group received a daily 1.P injection of Silymarin [100 mg/kg/day for 5 days,] 1hr after the last dose the rats were injected with a single I.P. injection of cisplatin [5 mg/kg]. A single dose of cisplatin [5 mg/kg I.P.] caused acute nephrotoxicity biochemically manifested as an increase in serum urea nitrogen [350%], serum creatinine [521%]. Serum nitric oxide was decreased. In the kidney tissue, treatment with cisplatin resulted in a significant 40%, 53% and 15% decrease in GSH, SOD and GSHPx, and a significant 75% and 80% increase in MDA and NO respectively as compared to saline-control group. Interestingly, administration of silymarin [100 mg/kg/day for 5 consecutive days] before administration of cisplatin attenuated cisplatin-induced nephrotoxicity manifested by normalizing the increase of serum urea, serum creatinine, MDA and NO in kidney tissues and the decrease in serum NO, GSH, SOD and GSHPx in kidney tissues. Data from this study suggest that silymarin attenuates cisplatin-induced nephrotoxicity