吗丙嗪对阿霉素作用下大鼠脂质过氧化的影响

Effect of probimane on lipid peroxidation caused by doxorubicin in rats

采用比色法测定GSH-Px,SOD活性及丙二醛含量,注射阿霉素后,大鼠全血、心肌中GSH-Px及红细胞SOD活性明显下降,心肌丙二醛含量显著升高,给予不同剂量的吗丙嗪后,GSH-Px及SOD活性有明显回升,并呈剂量依赖关系;而心肌丙二醛含量明显下降,提示阿霉素可能通过自由基途径对机体产生影响,而吗丙嗪通过提高体内抗氧化酶的活力,减轻脂质过氧化损伤而对心肌起保护作用。

Probimane (AT-2153) is a dio xopiperazine compound with antineoplastic, antimetastatic and radiopotentiation activities, and ex erimentally it can prevent the cardiotoxicity induced by doxorubicin (Dox) in mice. In order to tackle the mechanism of cardioprotective action of probimane against doxorubicin, the effect on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as the lipoperoxidation induced by Dox was studied. Injection of Dox resulted in a decrease in the SOD activity of erythrocytes and GSH-Px activities of the heart and plasma in rats. The decrease in SOD and GSH-Px activity caused by Dox could be prevented dose-dependently by the treatmentwith various doses of probimane. Probimane could also prevent lipid peroxidation induced by Dox, as manifested by the decrease in the malondialdehyde (MDA) content in the rat heart. The data suggest that lipoperoxidation caused by Dox may be resulted from its semiquinone free radical formation and probimane prevents Dox-induced cardiotoxicity by the inhibition of lipoperoxidation through its scavenging action on free radicals and the increase of SOD and GSH-Px activities.