Li Q, Bowmer C J, Yates M S
Department of Pharmacology, University of Leeds, UK.
J Pharm Pharmacol. 1995 Mar;47(3):223-6. doi: 10.1111/j.2042-7158.1995.tb05783.x.
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)
在大鼠中研究了甘氨酸（0.1 - 1.0 g kg⁻¹，静脉注射）对顺铂（6.0 mg kg⁻¹，静脉注射）所致肾血流动力学急性变化和肾毒性的影响。注射顺铂110分钟后，其导致[³H]菊粉清除率（CIN）和肾血流量（RBF）降低50%。0.1 g kg⁻¹剂量的甘氨酸并未减轻顺铂诱导的CIN或RBF降低。此外，该剂量的甘氨酸在顺铂注射后的7天内对肾功能无显著保护作用。相比之下，0.5或1.0 g kg⁻¹剂量的甘氨酸显著减轻了顺铂诱导的CIN和RBF下降，最高剂量在实验过程中完全防止了这些指标的任何下降。用这些较高剂量的甘氨酸治疗对顺铂的肾毒性作用产生了显著保护，这表现为一系列肾功能指标的改善，包括血浆尿素和肌酐浓度、尿量、钠排泄、CIN以及[¹⁴C]对氨基马尿酸清除率。0.25 g kg⁻¹甘氨酸中间剂量的实验结果显示，顺铂的急性肾血流动力学效应有一定程度的改善，特别是对于CIN；而在肾毒性研究中，0.25 g kg⁻¹甘氨酸使顺铂诱导的急性肾功能障碍有适度但显著的降低。结果表明，在注射顺铂的大鼠中，甘氨酸产生的急性肾血流动力学效应与甘氨酸在顺铂肾毒性中的长期肾保护作用之间存在明显关联。（摘要截断于400字）
