Nakano S, Gemba M
Division of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Jpn J Pharmacol. 1989 Jun;50(2):87-92. doi: 10.1254/jjp.50.87.
Effects of cis-diamminedichloroplatinum II (cisplatin), an antitumor agent with a dose-limiting effect of nephrotoxicity, on lipid peroxides and glutathione (GSH) were examined in rat kidney cortical slices treated with or without diethylmaleate (DEM), a GSH depletor, in vitro. DEM (3 mM) decreased the GSH level to about 16% of the control with a concomitant increase in lipid peroxides after 90 min of incubation. The same effects were obtained with 1 mM cisplatin 90 min later. Cisplatin (1 mM) with DEM (2 mM) stimulated both the decrease in GSH and the increase in lipid peroxides 90 min after incubation. However, cisplatin with DEM markedly stimulated lipid peroxidation with a small effect on the GSH decrease by cisplatin alone 30 min after incubation, while each drug by itself did not affect lipid peroxidation. The antioxidants N,N'-diphenyl-p-phenylene-diamine (DPPD), promethazine, and ascorbic acid abolished cisplatin-induced lipid peroxidation in the presence of DEM. DPPD had no effect on the depletion of GSH caused by cisplatin and DEM. Ascorbic acid and promethazine caused only a slight return towards the control level. The results suggested that cisplatin-induced lipid peroxidation is due to another mechanism in addition to the GSH depletion caused by the antitumor drug.
顺二氯二氨铂（顺铂）是一种具有肾毒性剂量限制作用的抗肿瘤药物，我们在体外对用或不用谷胱甘肽耗竭剂马来酸二乙酯（DEM）处理的大鼠肾皮质切片中，研究了顺铂对脂质过氧化物和谷胱甘肽（GSH）的影响。孵育90分钟后，DEM（3 mM）使GSH水平降至对照的约16%，同时脂质过氧化物增加。90分钟后，1 mM顺铂也产生了相同的效果。孵育90分钟后，顺铂（1 mM）与DEM（2 mM）共同作用刺激了GSH的降低和脂质过氧化物的增加。然而，孵育30分钟后，顺铂与DEM显著刺激了脂质过氧化，而单独顺铂对GSH降低的影响较小，而每种药物单独使用时均不影响脂质过氧化。抗氧化剂N，N'-二苯基对苯二胺（DPPD）、异丙嗪和抗坏血酸在存在DEM的情况下消除了顺铂诱导的脂质过氧化。DPPD对顺铂和DEM引起的GSH消耗没有影响。抗坏血酸和异丙嗪仅使GSH水平略有回升至对照水平。结果表明，顺铂诱导的脂质过氧化除了由抗肿瘤药物引起的GSH消耗外，还归因于另一种机制。
