Effect of trimetazidine on mitochondrial function and oxidative damage during reperfusion of ischemic hypertrophied rat myocardium.
The mitochondria harvested at the end of perfusion of control hearts and assayed for respiratory activity had a better function after ischemia and reperfusion following trimetazidine injection when glutamate was used as substrate. The protective effect of trimetazidine was enhanced when the mitochondria were isolated from hypertrophied perfused rat hearts. In fact the drug improved both the RCI and QO2 parameters with glutamate or succinate as substrates and raised the glutamate-induced QO2 value of mitochondria extracted from the hypertrophied heart perfused in aerobic conditions. In the aerobically perfused heart trimetazidine did not change either the levels of tissue malondialdehyde and lipofuscin, or the rate of mitochondrial O.2 generation while it reduced the O.2 formation and malondialdehyde content in the hypertrophied heart. After ischemia and reperfusion, the drug reproduced these protective effects in the hypertrophied hearts and reduced the level of tissue malondialdehyde in control hearts. The protective effect of trimetazidine against MDA formation was dose-dependent, being more evident at a higher dose (10 mumol/l). Preincubation of rat heart mitochondria with 0.1-10 mumol/l trimetazidine did not affect NADH oxidase, NADH dehydrogenase and NADH-cytochrome c reductase, succinate oxidase and cytochrome c oxidase activities. These results indicate that trimetazidine injected into isolated rat hearts protects against the damage induced on cardiac energetics and oxidative injuries by moderate ischemia and reperfusion stress, particularly in monocrotaline-induced hypertrophy in the rat heart. We suggest that trimetazidine reduces the formation of oxidative damage by preserving cardiac mitochondrial function.
Department of Biochemistry, University of Bologna, Italy.
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Guarnieri
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Muscari
D000818:Animals; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D014292:Trimetazidine / Q000494:pharmacology*
D014292:Trimetazidine