Mimić-Oka J, Simić T
Institute of Biochemistry Faculty of Medicine Belgrade, Yugoslavia.
Ren Fail. 1997 May;19(3):373-81. doi: 10.3109/08860229709047723.
Time-dependent alterations in glutathione (GSH) concentration and the activities of several key enzymes of GSH metabolism were studied in a rat model of experimental Fanconi syndrome induced by i.p. injection of sodium maleate (400 mg/kg BW). The changes in the parameters tested were monitored 0, 2, 4, and 12 h after sodium maleate administration. A significant decrease in renal GSH level was observed 2 and 4 h after sodium maleate treatment (27% and 38% of control values, respectively). The renal GSH depletion did not appear to be due to the decreased production rate or to an increased degradation of the tripeptide. This suggestion is based on the findings that the activities of the GSH synthesis (gamma-glutamyl cysteine synthetase and glutathione reductase) and those of the catabolic pathways (gamma-glutamyl transpeptidase) were unaltered at the same time points. The unchanged activity of gamma-glutamyl transpeptidase also suggests preserved luminal membrane integrity in experimental Fanconi syndrome. The decreased activity of glutathione peroxidase, which utilizes GSH as a cosubstrate in the course of inactivation of free radicals, in the first hours after treatment could facilitate lipid peroxidation reactions in this model of acute renal failure. The observed changes in all parameters tested were transient, with recovery to baseline levels in a period of 12 h after sodium maleate administration. At the same time a pronounced functional impairment still existed. The beneficial effect of fast recovery of renal GSH level on the functional and morphological restitution in experimental Fanconi syndrome is suggested.
在腹腔注射马来酸钠（400mg/kg体重）诱导的实验性范科尼综合征大鼠模型中，研究了谷胱甘肽（GSH）浓度随时间的变化以及GSH代谢几种关键酶的活性。在给予马来酸钠后0、2、4和12小时监测测试参数的变化。在马来酸钠处理后2小时和4小时观察到肾GSH水平显著降低（分别为对照值的27%和38%）。肾GSH耗竭似乎不是由于三肽的生成速率降低或降解增加所致。这一推测基于以下发现：在相同时间点，GSH合成酶（γ-谷氨酰半胱氨酸合成酶和谷胱甘肽还原酶）以及分解代谢途径（γ-谷氨酰转肽酶）的活性未发生改变。γ-谷氨酰转肽酶活性未改变也表明在实验性范科尼综合征中肾小管腔膜完整性得以保留。在处理后的最初几个小时内，利用GSH作为共底物使自由基失活的谷胱甘肽过氧化物酶活性降低，这可能会促进该急性肾衰竭模型中的脂质过氧化反应。所观察到的所有测试参数的变化都是短暂的，在给予马来酸钠后12小时内恢复到基线水平。与此同时，明显的功能损害仍然存在。提示肾GSH水平快速恢复对实验性范科尼综合征的功能和形态恢复具有有益作用。
