EVIDENCE FOR THE INVOLVEMENT OF NITRIC-OXIDE IN CISPLATIN-INDUCED TOXICITY IN RATS

Cisplatin treatment of rats results into a significant increase in the activity of Ca2+-independent nitric oxide synthase (NOS) in kidneys a nd liver. Significant enhancement of lipid peroxidation in gastric muc osa, kidneys and liver was also observed. The administration of N-G-ni tro-L-arginine methyl ester, an inhibitor of NOS, markedly reduced ren al and gastrointestinal toxicity, and also decreased the content of bl ood urea nitrogen, serum creatinine, and incidence of diarrhoea along with a significant inhibition in lipid peroxidation in the target orga ns. The present report, while demonstrating the beneficial effect of t he blockade of NO pathways during cisplatin chemotherapy, may be helpf ul in developing strategies for combating some of the toxic side-effec ts of the drug.