Mayer R D, Cockett A T
Department of Urology, University of Rochester School of Medicine, NY 14642.
J Biochem Toxicol. 1988 Fall;3:213-21. doi: 10.1002/jbt.2570030307.
The unprecedented ability of cyclosporin A, when given for six days at a dose of 25 mg/kg/d or 50 mg/kg/d, to cause a marked and sustained increase in renal glutathione (GSH) concentration in rat kidney is described. This response was particular to the kidney insofar as the GSH concentration in the liver was not increased in response to a lower dose of cyclosporin and was decreased in the liver of animals treated with the higher dose of the drug. The increase in kidney GSH concentration did not appear to be due to an increased rate of production or to an inhibition of the degradation of the tripeptide. This suggestion is based on the finding that the activities of the GSH synthesis pathways, GSSG-reductase and gamma-glutamylcysteine synthetase, were unchanged or decreased, respectively, and those of the catabolic enzymes, GSH-peroxidase and gamma-glutamyltranspeptidase, were unchanged or increased, respectively. It is suggested that the elevation of renal GSH content in the face of diminished synthetic capacity and an apparent increased utilization may result from an enhanced uptake of GSH as the result of alterations caused by cyclosporin in the renal transport system.
描述了环孢素A在以25mg/kg/d或50mg/kg/d的剂量给药6天时，能够使大鼠肾脏中的谷胱甘肽（GSH）浓度显著且持续升高，这种能力是前所未有的。这种反应在肾脏中是特有的，因为较低剂量的环孢素不会使肝脏中的GSH浓度升高，而较高剂量药物处理的动物肝脏中的GSH浓度会降低。肾脏GSH浓度的升高似乎不是由于三肽生成速率增加或降解受到抑制。这一推测基于以下发现：GSH合成途径、谷胱甘肽二硫化物还原酶和γ-谷氨酰半胱氨酸合成酶的活性分别未改变或降低，而分解代谢酶谷胱甘肽过氧化物酶和γ-谷氨酰转肽酶的活性分别未改变或升高。有人提出，在合成能力减弱和明显利用率增加的情况下，肾脏GSH含量的升高可能是由于环孢素对肾脏转运系统造成改变，从而增强了GSH的摄取所致。
