Sodium nitroprusside and l -arginine attenuates ferric nitrilotriacetate-induced oxidative renal injury in rats

• Published in: Toxicology (Amsterdam) Vol. 232; no. 3; pp. 183 - 191
• Main Authors: Gupta, Amit, Chander, Vikas, Sharma, Sameer, Chopra, Kanwaljit
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 11.04.2007
• Subjects: Animals; Arginine - pharmacology; Blood Urea Nitrogen; Creatinine - blood; Drug Interactions; Emergency; Enzyme Inhibitors - pharmacology; Ferric Compounds - antagonists & inhibitors; Ferric Compounds - toxicity; Glutathione - blood; Histocytochemistry; Kidney Diseases - chemically induced; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidney Diseases - prevention & control; l-Arginine; l-NAME; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Nitrilotriacetic Acid - analogs & derivatives; Nitrilotriacetic Acid - antagonists & inhibitors; Nitrilotriacetic Acid - toxicity; Nitroprusside - pharmacology; Rats; Rats, Wistar; Renal failure; Sodium nitroprusside; Superoxide Dismutase - blood; Thiobarbituric Acid Reactive Substances - metabolism; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - blood; Tumor necrosis factor-α; Sodium nitroprusside; l-Arginine; Tumor necrosis factor-α; l-NAME; Nitric oxide; Renal failure
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2007.01.009

Abstract The role of nitric oxide (NO) in acute renal failure (ARF) is debatable. In the present study, we investigated the effect of acute administration of NO donor, Sodium nitroprusside (SNP), l -Arginine ( l -Arg) and NO synthase inhibitor, N (omega)- l -arginine methyl ester ( l -NAME) in Fe-NTA induced renal toxicity. Rats were pretreated with SNP (2.5 mg/kg i.p), l -Arg (125 mg/kg, i.p.) and l -NAME (10 mg/kg, i.p.) prior to administration of Fe-NTA (8 mg iron/kg body weight, i.p.) to determine the urea and creatinine levels along with biochemical analysis of oxidative stress. Fe-NTA administration markedly increased the BUN and serum creatinine level which was coupled with a marked lipid peroxidation, decreased levels of reduced glutathione and total nitric oxide levels of rat kidneys coupled with significant morphological alterations. It also resulted in the significant increase in tumor necrosis factor-α (TNF-α) in serum. Concomitant treatment with SNP and l -Arg significantly reduced the serum creatinine and BUN levels, reduced lipid peroxidation in a significant manner, restored levels of reduced glutathione, increased total nitric oxide levels and restored the normal morphology. Pretreatment with SNP and l -Arg attenuated the levels of TNF-α in serum in a significant manner. Prior administration of l -NAME reversed the protective effects produced by SNP and l -Arg. Present findings strongly suggest that nitric oxide plays a significant role in the pathophysiology of iron-induced renal failure and administration of NO donors can be valuable in the treatment of ARF.