Hanigan M H, Gallagher B C, Taylor P T
Department of Cell Biology, University of Virginia, Charlottesville 22908, USA.
Am J Obstet Gynecol. 1996 Aug;175(2):270-3; discussion 273-4. doi: 10.1016/s0002-9378(96)70134-5.
Inhibition of gamma-glutamyl transpeptidase activity by acivicin or a large bolus of intravenous glutathione blocks the nephrotoxicity of cisplatin. The purpose of this study was to determine whether these compounds inhibit nephrotoxicity by reducing the amount of platinum retained by the kidney.
The platinum concentration in urine and kidney of cisplatin-treated rats was determined by graphite furnace atomic absorption spectroscopy. Tissues from three experimental groups of rats were analyzed. The first group was treated with a nephrotoxic dose of cisplatin. The second group was treated with acivicin before cisplatin. The third group received a bolus of glutathione before cisplatin. Urine collected for 3 hours after the injection of cisplatin and kidney tissue from animals 5 days after treatment were analyzed for platinum content.
Urine from animals pretreated with acivicin had the same concentration of platinum as that of control animals treated with cisplatin alone. Analysis of kidney tissue, blood urea nitrogen and serum creatinine 5 days after treatment showed that pretreatment with acivicin or glutathione blocked the nephrotoxicity of cisplatin. However, these agents did not alter the concentration of platinum in the kidney.
The data in this study reveal that pretreatment with acivicin or glutathione does not block the uptake of platinum into the kidney nor do these agents reduce the concentration of platinum retained by the kidney. The mechanism by which these agents may inhibit the nephrotoxicity of cisplatin is discussed.
阿西维辛或大剂量静脉注射谷胱甘肽对γ-谷氨酰转肽酶活性的抑制作用可阻断顺铂的肾毒性。本研究的目的是确定这些化合物是否通过减少肾脏中铂的潴留量来抑制肾毒性。
采用石墨炉原子吸收光谱法测定顺铂处理大鼠尿液和肾脏中的铂浓度。对三组实验大鼠的组织进行分析。第一组用肾毒性剂量的顺铂处理。第二组在顺铂处理前用阿西维辛处理。第三组在顺铂处理前接受一次大剂量的谷胱甘肽。分析注射顺铂后3小时收集的尿液以及处理后5天动物的肾脏组织中的铂含量。
用阿西维辛预处理的动物尿液中铂的浓度与仅用顺铂处理的对照动物相同。处理后5天对肾脏组织、血尿素氮和血清肌酐的分析表明，用阿西维辛或谷胱甘肽预处理可阻断顺铂的肾毒性。然而，这些药物并未改变肾脏中铂的浓度。
本研究数据显示，用阿西维辛或谷胱甘肽预处理既不阻断铂进入肾脏，也不降低肾脏中铂的潴留浓度。讨论了这些药物可能抑制顺铂肾毒性的机制。
