Amelioration of cisplatin nephrotoxicity with glycine: dose dependency in rats.
The effects of glycine (0.1-1.0 g kg-1, i.v.) on the acute changes in renal haemodynamics and nephrotoxicity produced by cisplatin (6.0 mg kg-1, i.v.) were investigated in the rat. Cisplatin produced decreases of 50% in the clearance of [3H] inulin (CIN) and renal blood flow (RBF), 110 min following its injection. Glycine at a dose of 0.1 g kg-1 produced no attenuation of the cisplatin-induced decrease in CIN or RBF. Furthermore, this dose of glycine provided no significant protection of renal function over a 7-day period following cisplatin injection. By contrast, glycine at a dose of either 0.5 or 1.0 g kg-1 markedly attenuated cisplatin-induced falls in CIN and RBF, with the highest dose completely preventing any falls in these indices during the course of the experiment. Treatment with these higher doses of glycine produced prominent protection from the nephrotoxic actions of cisplatin, as evidenced by improvements in a range of indices of renal function which included plasma urea and creatinine concentrations, urine output, sodium excretion, CIN and the clearance of [14C] p-aminohippurate. The results of experiments with an intermediate dose of 0.25 g kg-1 glycine revealed some degree of amelioration of acute renal haemodynamic effects of cisplatin, particularly with regard to CIN; whilst in the nephrotoxicity study, 0.25 g kg-1 glycine produced a modest but significant reduction in cisplatin-induced acute renal dysfunction. The results have revealed a clear association between the acute renal haemodynamic effects produced by glycine in cisplatin-injected rats with the longer-term renal protective effects of glycine in cisplatin nephrotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
Li
Q
Q
Department of Pharmacology, University of Leeds, UK.
Bowmer
C J
CJ
Yates
M S
MS
D000704:Analysis of Variance; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007444:Inulin / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007677:Kidney Function Tests; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D014508:Urea / Q000097:blood; D010130:p-Aminohippuric Acid / Q000652:urine
D014508:Urea; D007444:Inulin; D003404:Creatinine; D002945:Cisplatin; D005998:Glycine; D010130:p-Aminohippuric Acid