Mitochondrial antioxidant plastomitin alters the myocardial energy state and prevented the development of systolic dysfunction in doxorubicin-induced cardiomyopathy (original) (raw)
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Background. Doxorubicin is the most widely used drug among anthracyclines. However, despite its clinical effectiveness, the cardiotoxic effect is observed in approximately 25,0% of patients, thus limiting its use. Although significant success in understanding individual pathogenetic elements of the cardiotoxic effect of this drug has been achieved, cancer patients who have doxorubicin-induced cardiac complications are currently treated mostly with drugs for cardiac insufficiency because there is no specific treatment for anthracycline cardiomyopathy. Purpose – to characterize the effect of placenta cryoextract on the course of doxorubicin myocardial injury on the model of chronic doxorubicin cardiomyopathy compared to reference drug vinboron according to the data of biochemical analyses of the heart tissues. Materials and methods. Chronic doxorubicin cardiomyopathy was modeled by the means of injection of doxorubicin hydrochloride at the rate of 5 mg/kg of body weight once a week fo...
Innovative Medicine of Kuban
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Изучены возможности лазерной конфокальной микроскопии в анализе объема липидных частиц и количества функционально-активных митохондрий и продукции активных форм кислорода в клетках печени для ранней диагностики цитохимических нарушений при дислипопротеидемии. Оценен потенциал анализа уровня мтДНК плазмы крови на ранних сроках развития дислипопротеидемии и при экспериментальном инфаркте миокарда. Полученные данные будут служить основой для создания технологий диагностического мониторинга выраженности атеросклероза и инфаркта миокарда.
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In experiments in vitro on the mitochondria isolated from the rat's heart we studied the effects of the openers of ATP-sensitive potassium channels (K(ATP)-channels), flocalin and tioflocalin, on the calcium-induced mitochondrial pore (MPTP) opening. Flocalin and tioflocalin caused moderate Ca(2+)-independent mitochondria swelling, which was prevented by a specific inhibitor of 5-hydroxydecanoate. This allowed to identify these compounds as mitochondrial K(ATP)-channels openers. We found that concentration-dependent inhibitory effects (10(-7) to 10(-4) M) of flocalin (with IC50 = 50 microM) and tioflocalin (with IC50 = 2,7 microM) on Ca(2+)-induced mitochondrial swelling (MPTP opening) in the heart characterized more powerful cardioprotective action of the latter. It was shown that the administration of these compounds in experiments in vivo decreased the sensitivity of the MPTP opening to Ca2+. Thus, under physiological conditions the activators K(ATP)-channels probably provide...