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Objective . Nitric oxide (NO) has numerous important functions in the kidney. The role of NO in cisplatin (CP)-induced nephrotoxicity is not completely understood. This study was designed to determine the role of NO synthase inhibitor (L-NAME) on the severity of CP-induced nephrotoxicity in rats.  Methods . Sixty four male (M) and female (F) Wistar rats were randomly divided into eight groups. The sham groups (group 1, male,  n  = 6 and group 2, female,  n  = 6) received saline. Groups 3 (male,  n  = 8) and 4 (female,  n  = 8) were treated with L-NAME (4 mg/kg, i.p.), and groups 5 (male,  n  = 8) and 6 (female,  n  = 8) received CP (3 mg/kg) for 7 days. Groups 7 (male,  n  = 8) and 8 (female,  n  = 8) were treated with L-NAME and CP for 7 days.  Results . The CP-alone treated rats showed weight loss and increase in serum levels of blood urea nitrogen (BUN) and creatinine (Cr). Coadministration of L-NAME and CP did not improve weight loss, and it increased the levels of BUN and Cr in male but not in female rats ( P  < 0.05). CP alone increased kidney damage significantly ( P  < 0.05 ), however, the damage induced by combination of CP and L-NAME was gender-related.  Conclusion . NOS inhibition by L-NAME increased CP-induced nephrotoxicity, which was gender-related.

Inhibition of Nitric Oxide Synthase by L-NAME Promotes Cisplatin-Induced Nephrotoxicity in Male Rats