The protective effect of glycine in cisplatin nephrotoxicity: inhibition with NG-nitro-L-arginine methyl ester.
The effect of glycine on the acute changes in renal haemodynamics and nephrotoxicity produced by cisplatin was investigated in the rat. Cisplatin (6.0 mg kg-1, i.v.) injection in anaesthetized rats produced, over a period of 2 h, falls of approximately 50% in renal blood flow (RBF) and the clearance of [3H]inulin (CLIN), effects which were prevented by co-administration of glycine (1.0 g kg-1). Infusion of the nitric oxide (NO) synthase-inhibitor NG-nitro-L-arginine methyl ester, L-NAME (10 micrograms min-1 kg-1, i.v.), abolished glycine's ability to maintain RBF in cisplatin-injected rats whilst partially inhibiting the ability of glycine to preserve CLIN. Treatment of cisplatin-injected rats with glycine (1.0 g kg-1, i.v.) significantly ameliorated the nephrotoxic effects of cisplatin (6.0 mg kg-1) as judged by improvements in a range of indices of renal function which included plasma urea and creatinine concentrations, urine output, sodium excretion, CLIN and the clearance of [14C]p-aminohippurate. Administration of L-NAME (1.0 mg kg-1, i.v.) to rats which received cisplatin and glycine significantly inhibited the reno-protective effect of glycine. However, L-NAME administration to rats which were treated only with cisplatin did not result in any potentiation of cisplatin nephrotoxicity. The findings of this study suggest that glycine can block the acute falls in RBF and CIN produced by cisplatin by a mechanism which involves the production of NO. Furthermore, the results indicate that these renal haemodynamic actions of glycine are responsible, at least in part, for the ability of this amino acid to ameliorate cisplatin nephrotoxicity.
Li
Q
Q
Department of Pharmacology, University of Leeds, UK.
Bowmer
C J
CJ
Yates
M S
MS
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D005998:Glycine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine
D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium; D003404:Creatinine; D002945:Cisplatin; D005998:Glycine; D019331:NG-Nitroarginine Methyl Ester