The Evaluation of L-arginine Prophylaxis and Treatment on Preventing Nephrotoxicity Cisplatin-Induced in Rat: Role of Gender Difference

Nephrotoxicity is the main side effect of cisplatin (CP)-therapy which is induced by oxidative stress. Nephrotoxicity is gender related and limits the cisplatin treatment. Therefore, it is essential to prevent or to ameliorate cisplatin-induced nephrotoxicity via administration of supplementations. This study was designed to investigate the effect of L-arginine (L-Arg) prophylaxis and treatment on preventing cisplatin-induced nephrotoxicity in male and female rats. Sixteen male and twenty female Wistar rats were divided into eight groups. Groups 1 (male) and 5(female), as positive control groups, received cisplatin (2.5 mg/kg/day; Intraperitoneally) for a week. Groups 2 (male) and 6 (female) received L-arginine (150 mg/kg/day; Intraperitoneally) as prophylaxis for 3 days, and cisplatin was administered from the day 3 for a week. Groups 3 (male) and 7 (female) received L-arginine, as prophylaxis for 3 days; and cisplatin was administered from the day 3, for a week, without withdrawal of daily L-arginine administration. Groups 4 (male) and 8 (female) received cisplatin and L-arginine simultaneously for a week. On the day 10, blood samples were taken and kidneys were prepared for histopathological investigation. L-arginine administration did not changed the measured parameters from positive control group in females. Simultaneous administration of cisplatin and L-arginine decreased serum levels of blood urea nitrogen and creatinine as well as intensity of renal tissue damage in comparison with positive control group in males (P < 0.05). In addition, it ameliorated kidney weight in comparison with positive control group in male, insignificantly (P = 0.20). No significant difference was observed in tissue nitrite level among male groups and L-arginine treated male groups had body weight loss more than positive control group (P < 0.05). Simultaneous administration of L-arginine, as nitric oxide precursor, and cisplatin could ameliorate cisplatin-induced nephrotoxicity in male gender through improving endothelium function.