Sodium nitroprusside and L-arginine attenuates ferric nitrilotriacetate-induced oxidative renal injury in rats.
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-alpha (TNF-alpha) 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-alpha 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.
Gupta
Amit
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Chander
Vikas
V
Sharma
Sameer
S
Chopra
Kanwaljit
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005290:Ferric Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005978:Glutathione / Q000097:blood; D006651:Histocytochemistry; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood
D004791:Enzyme Inhibitors; D005290:Ferric Compounds; D020030:Nitric Oxide Donors; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D003404:Creatinine; D013482:Superoxide Dismutase; D005978:Glutathione; D009571:Nitrilotriacetic Acid; D019331:NG-Nitroarginine Methyl Ester; C020326:ferric nitrilotriacetate