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

Abstract

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.