Protective effect of L-arginine against nephrotoxicity induced by cyclosporine in normal rats.
Effects of L-arginine (L-arg) and aminoguanidine (AG) on the nephrotoxicity induced by cyclosporine (CsA) were investigated. After injection of CsA (15 mg kg(-1) day (-1)i.p. for 10 days), it induced nephrotoxicity, manifested biochemically by a significant elevation of serum urea and creatinine. In addition, a marked increase in lipid peroxides measured as malondialdehyde (MDA) as well as a significant decrease in glutathione peroxidase (GSH-Px) activity (EC.1.11.1.9) and reduced glutathione content (GSH) in kidney tissues homogenate were observed. Nephrotoxicity was further confirmed by histopathological investigation. Oral administration of L-arg (300 mg kg (-1)day(-1) orally) for 5 days before and 10 days concomitant with CsA injection produced a significant protection against nephrotoxity induced by CsA. The amelioration of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations. In addition, L-arg prevented the rise of MDA as well as reduction of GSH-Px activity and reduced GSH content in kidney tissue. The protective effects of L-arg against CsA-induced nephrotoxicity were further confirmed by histopathological examination. However, oral supplementation of AG (100 mg kg (-1)day(-1) p.o.) did not protect the kidney from the damaging effects of CsA. These results suggest that L-arg can ameliorate kidney dysfunction induced by CsA via a mechanism(s) which involves the production of nitric oxide. In addition, L-arg may therefore be a beneficial remedy for CsA nephrotoxicity and can be used to improve the therapeutic index of CsA.
Mansour
Mahmoud
M
Department of Pharmacology, King Saud University, P.O. Box 2457, Riyadh 11451, Kingdom of Saudi Arabia. mahmedm@ksu.edu.sa
Daba
Mohammad Hesham
MH
Gado
Ali
A
Al-Rikabi
Ammar
A
Al-Majed
Abdulhakeem
A
D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors; D006146:Guanidines / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000097:blood
D004791:Enzyme Inhibitors; D006146:Guanidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014508:Urea; D001120:Arginine; D003404:Creatinine; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; C004479:pimagedine