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 Ca(2+)-independent nitric oxide synthase (NOS) in kidneys and liver. Significant enhancement of lipid peroxidation in gastric mucosa, kidneys and liver was also observed. The administration of NG-nitro-L-arginine methyl ester, an inhibitor of NOS, markedly reduced renal and gastrointestinal toxicity, and also decreased the content of blood urea nitrogen, serum creatinine, and incidence of diarrhoea along with a significant inhibition in lipid peroxidation in the target organs. The present report, while demonstrating the beneficial effect of the blockade of NO pathways during cisplatin chemotherapy, may be helpful in developing strategies for combating some of the toxic side-effects of the drug.
Srivastava
R C
RC
Industrial Toxicology Research Centre, Lucknow, India.
Farookh
A
A
Ahmad
N
N
Misra
M
M
Hasan
S K
SK
Husain
M M
MM
D000818:Animals; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D051381:Rats
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D003404:Creatinine; D019001:Nitric Oxide Synthase; D002945:Cisplatin; D019331:NG-Nitroarginine Methyl Ester