L-arginine ameliorates kidney function and urinary bladder sensitivity in experimentally-induced renal dysfunction in rats.
Effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on the renal dysfunction that is induced by cisplatin (CDDP) were investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced renotoxicity, which was manifested by increasing the sensitivity of isolated urinary bladder rings to acetylcholine (ACh), together with a significant elevation of serum urea and creatinine, and a severe decrease in serum albumin. Moreover, renal dysfunction was further confirmed by a significant decrease of enzyme activities, such as glutathione peroxidase, GSH-Px (E.C 1.11.1.9), catalase (E.C 1.11.1.6), as well as a significant increase in lipid peroxides that were measured as malondialdhyde (MDA) in kidney tissue homogenates. The administration of L-arginine (70 mg/kg/d p.o in drinking water 5 d before and 5 d after the CDDP injection) significantly ameliorated the renotoxic effects of CDDP, as judged by restoring the normal responses of isolated bladder rings to Ach, and also by an improvement in a range of renal function indices, which included serum urea and creatinine concentrations and kidney weight. In addition, L-arginine prevents the rise of MDA, as well as a reduction of GSH-Px and catalase activities in kidney tissues homogenates. On the other hand, the administration of L-NAME (4 mg/kg/d p.o) resulted in no protection against renal dysfunction that was induced by CDDP treatment. The findings of this study suggest that L-arginine can attenuate kidney injury that is produced by CDDP treatment. In addition, L-arginine may be a beneficial remedy for CDDP-induced renal toxicity, and could be used to improve the therapeutic index of CDDP.
Mansour
Mahmoud A
MA
Department of Pharmacology, College of Pharmacy, King Saud University, P.O Box 2457, Riyadh 11451, Saudi Arabia. mansour1960us@yahoo.com
Al-Shabanah
Othman A
OA
El-Khashef
Hassan A
HA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D007677:Kidney Function Tests; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D014508:Urea / Q000097:blood; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D000970:Antineoplastic Agents; D008054:Lipid Peroxides; D014508:Urea; D001120:Arginine; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione; D000109:Acetylcholine; D002945:Cisplatin; D019331:NG-Nitroarginine Methyl Ester