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

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.