The Protective Effect of Glycine in Cisplatin Nephrotoxicity: Inhibition with NG-Nitro-l-arginine Methyl Ester

Author:

Li Q1,Bowmer C J1,Yates M S1

Affiliation:

1. Department of Pharmacology, Worsley Medical and Dental Building, The University of Leeds, Leeds LS2 9JT, UK

Abstract

Abstract 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 μg 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.

Funder

Henry Lester Trust and Great Britain-China Educational Trust

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference18 articles.

1. Effects of calcium antagonists on renal hemodynamics and glomerular function;Carmines;Kidney Int.,1992

2. Renal and systemic effects of aminoacids administered separately: comparison between l-arginine and non-nitric oxide donor aminoacids;Cernadas;J. Pharmacol. Exp. Ther.,1992

3. Role of endothelium-derived nitric oxide in the renal haemodynamic response to amino acid infusion;Chen;Am. J. Physiol.,1992

4. Acute effect of cisplatin on renal hemodynamics and tubular function in dog kidneys;Daugaard;Renal Physiol.,1986

5. Functional and histopathological changes in dog kidneys after administration of cisplatin;Daugaard;Renal Physiol.,1987

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3