[Effect of trimetazidine on membrane changes induced by oxygen free radicals in human red cells].

It is well known that oxygen free radicals are generated in different ischaemic tissues and can mediate cell injury. Furthermore, a loss of intracellular potassium is involved in heart ischemia. We previously developed a method to study a possible connection between these two phenomena in human erythrocytes treated in vitro with an oxygen free radical generator: phenazine methosulfate. We showed that transport systems specific to potassium are poorly inhibited (sodium-potassium pump; sodium-potassium cotransport) or unaffected (Gardos effect, chlorine-dependent potassium transport); that the erythrocyte potassium loss is essentially due to an increase in passive potassium permeability resulting from lipid peroxidation and that alterations of transport pathways are enhanced by diethyldithiocarbamate, a superoxide dismutase inhibitor. On the other hand, a cardioprotective drug, trimetazidine, indicated in ischaemic heart disease, which has no calcium antagonist action or coronary vasodilator effect, was studied as a possible candidate for preventing such damage by free radicals. Red cells collected from healthy donors previously treated with trimetazidine were incubated in vitro with phenazine methosulfate and diethyldithiocarbamate. We observed significant decreases in oxygen free radical-dependent passive potassium permeability and lipid peroxidation. This strongly suggests that trimetazidine possesses a free radical scavenger activity which may explain its cardioprotective role.