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[硫醇依赖性保护系统在饮食预防卡米诺霉素毒性作用中的应用]

[Thiol-dependent protective systems in alimentary prevention of the toxic effect of carminomycin].

作者信息

Lenskaia E G, Tazhibaev Sh S, Alekseeva N R, Monakhov B V, Karsybekova N M, Sisemalieva Zh S, Sarbaev B T

出版信息

Antibiot Khimioter. 1990 Apr;35(4):36-9.

PMID:2383144
Abstract

The state of the thiol-dependent systems i.e. concentration of the SH-groups, activity of glutathione reductase and glutathione-S-transferase, carminomycin antitumor and toxic effects was studied under conditions of tumor growth and carminomycin therapy with the use of prophylactic rations (PR) aimed at stimulating the cell thiol-dependent and antioxidant systems for decreasing the drug toxic action. It was shown that addition of sulfur-containing amino acids, selenium and vitamin E to the ration of healthy and tumor-bearing rats (Walker carcinosarcoma 256) induced a decrease in the level of the SH-groups in the liver just likely promoting efficient extrahepatic usage of glutathione. After administration of carminomycin a long with the PR use, the liver showed the thiol-preserving capacity evidenced by a decrease or complete elimination of the above effect of the ration. The use of PR resulted in a marked increase in the glutathione-S-transferase activity in cytosol and to a lesser extent in the liver microsomes. A regulating effect of the PR on the activity of glutathione reductase was observed: its inhibition in the healthy animals and stimulation after carminomycin administration in the heart of the healthy animals and the liver of the tumor-bearing animals.

摘要

在肿瘤生长和使用旨在刺激细胞硫醇依赖性和抗氧化系统以降低药物毒性作用的预防性日粮(PR)进行卡米诺霉素治疗的条件下,研究了硫醇依赖性系统的状态,即SH基团的浓度、谷胱甘肽还原酶和谷胱甘肽-S-转移酶的活性、卡米诺霉素的抗肿瘤和毒性作用。结果表明,在健康大鼠和荷瘤大鼠(Walker癌肉瘤256)的日粮中添加含硫氨基酸、硒和维生素E,可导致肝脏中SH基团水平降低,这可能促进了谷胱甘肽在肝外的有效利用。在使用PR的同时给予卡米诺霉素后,肝脏表现出硫醇保留能力,这表现为日粮上述作用的降低或完全消除。使用PR导致细胞质中谷胱甘肽-S-转移酶活性显著增加,而在肝脏微粒体中的增加程度较小。观察到PR对谷胱甘肽还原酶活性有调节作用:在健康动物中对其有抑制作用,而在健康动物心脏和荷瘤动物肝脏中给予卡米诺霉素后则有刺激作用。

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