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Evaluation of prophylactic and therapeutic effects of N-acetylcysteine on cisplatin-induced nephrotoxicity in rats.
Cisplatin, an alkylating agent, is widely used in the treatment of testicular and ovarian germ-cell tumors. When cisplatin is administered, nephrotoxicity occurs in approximately one-third of the patients and is associated with high levels of mortality. There are only a few experimental data for the prophylactic and therapeutic effects of antioxidant agents on cisplatin-induced renal injury. The present study was designed to determine the protective effect of N-acetylcysteine on cisplatin-induced nephrotoxicity in rats and to evaluate the underlying mechanism of this effect. Forty-eight albino Wistar male rats were divided into three groups of 16 rats each. Group 1 served as the control group. Group 2 received a single intraperitoneal dose of 10mg/kg cisplatin, whereas group 3 received a single intraperitoneal dose of 10mg/kg cisplatin and N-acetylcysteine (200mg/kg/day) was administered p.o. for 5 days. Blood urea nitrogen and serum creatinine levels were measured for the evaluation of renal function. Kidney tissue malondialdehyde and nitric oxide levels were also determined. Histopathologic sections of the kidney were examined. Compared with the control group, the levels of blood urea nitrogen, serum creatinine, malondialdehyde, and nitric oxide levels in the group that received cisplatin were significantly higher. Treatment of N-acetylcysteine to the group that received cisplatin attenuated the increase in blood urea nitrogen and serum creatinine levels, decreased malondialdehyde and nitric oxide levels, and ameliorated renal histopathologic changes. Treatment of N-acetylcysteine did not influence the levels of blood urea nitrogen and serum creatinine in the control group compared to those in the

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