ABSTRACT

Increase of lipid peroxidation and glutathione (GSH) depletion in kidney tissues have been observed in rats with cisplatin-(CDDP) induced nephrotoxicity. This investigation elucidates the role of L-arginine, the substrate of nitric oxide synthase (NOS), on renal injury, lipid peroxidation and urinaiy excretion of nitrite (NO2-)+ nitrate (NO3-) in rats with CDDP induced renal failure. CDDP (3 mg/kg, once a day) was injected intraperitoneally for 5 days. In subgroups, daily L-arginine (0.2g/lcg) or NG-nitro-L-arginine methyl ester (L-NAME) (NOS inhibitor, 20 mg/kg) were administrated intraperitonally 1 hour prior to CDDP treatment. Treatment with CDDP resulted in significant increase plasma creatinine (Cr), urea levels, daily urine volume, urinaiy gamma glutamyl transferase (GGT) levels and significant decrease creatinine clearance and urinaiy NO2 +NO3 excretion. Intraperitoneal administration of L-arginine in the low dose prevented the CDDP induced elevation of plasma Cr and urea levels. When compared with controls, CDDP administration resulted in increased lipid peroxidation and decreased GSH levels in the kidney; L-arginine reversed these effects. In addition, pretreatment of L-arginine was effective in the normalization of daily urine volume and urinary excretion of NO2 +NO3. On the other hand, the administration of L-NAME resulted in no protection against CDDP-induced renal damage. The findings of this study suggest that intraperitoneal L-arginine administration can prevent the CDDP-induced renal damage by a mechanism which involves the production of NO.