[丙二醛对阿霉素在大鼠心脏中形成半醌自由基的清除作用]

[Scavenging of probimane on semiquinone free radical formation by doxorubicin in rat heart].

作者信息

Zhang Y, Zhang T M, Zhao B L, Han J K, Chen W C, Xin W J

机构信息

He-nan Institute of Medical Sciences, Zhengzhou, China.

出版信息

Zhongguo Yao Li Xue Bao. 1991 Jan;12(1):20-3.

PMID:1950578

Abstract

Probimane, dl-bis (4-morpholin-methyl 3,5-dioxopipweazin-1-yl) propane first synthesized in China, is a dioxopiperazin compound with antineoplastic, antimetastatic and radiopotentiating activities. In order to evaluate the mechanisms of cardiotoxicity protective action of probimane, the free radical induced by doxorubicin were analysed by electron spin resonance (ESR) techniques. Our studies showed that doxorubicin stimulated the formation of semiquinone free radicals in the rat heart homogenate and heart cell mitochondria systems, and probimane inhibited the free radical formation in both systems, with the dose-dependent and time-dependent responses. The inhibitory rates of doxorubicin free radical formation in rat heart homogenate system by probimane 0.6 mmol.L-1 at time of 3, 5, 10, 15, 30, 45 and 60 min were 44.6%, 43.0%, 51.5%, 74.3%, 68.1%, 56.1% and 39.9% respectively. The inhibitory rates of semiquinone free radical formation in mitochondria system by probimane at the concentration of 0.02, 0.06, 0.6, 1.2 and 2.4 mmol.L-1 were 17.07%, 29.87%, 63.95%, 64.62% and 83.64%, respectively. Probimane had no effect on NADH2, but inhibited NADH dehydrogenase activity at higher concentration.

摘要

丙亚胺，即dl-双（4-吗啉甲基-3,5-二氧代哌嗪-1-基）丙烷，最早在中国合成，是一种具有抗肿瘤、抗转移和放射增敏活性的二氧代哌嗪化合物。为了评估丙亚胺心脏毒性保护作用的机制，采用电子自旋共振（ESR）技术分析了阿霉素诱导的自由基。我们的研究表明，阿霉素刺激大鼠心脏匀浆和心脏细胞线粒体系统中半醌自由基的形成，而丙亚胺在这两个系统中均抑制自由基的形成，具有剂量依赖性和时间依赖性反应。在3、5、10、15、30、45和60分钟时，0.6 mmol.L-1丙亚胺对大鼠心脏匀浆系统中阿霉素自由基形成的抑制率分别为44.6%、43.0%、51.5%、74.3%、68.1%、56.1%和39.9%。在0.02、0.06、0.6、1.2和2.4 mmol.L-1浓度下，丙亚胺对线粒体系统中半醌自由基形成的抑制率分别为17.07%、29.87%、63.95%、64.62%和83.64%。丙亚胺对NADH2无影响，但在较高浓度下抑制NADH脱氢酶活性。