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.