Linnyk O. Disturbances of mitochondrial apparatus of cardiomyocytes under doxorubicin-induced oxidative stress: mechanisms and correction

Dissertation is devoted to investigation of mitochondrial function violations in cardiomyocytes under the influence of the doxorubicin-induced oxidative stress and the possibility of their correction by curcumin in vitro and in vivo. In the neonatal cardiomyocytes culture and rat myocardium, there was shown that doxorubicin exposure leads to induction of oxidative stress, the respiratory chain efficiency reduction, a decrease in energetic regulation of mitochondrial respiration, declining of the rate of K+ entry to the isolated mitochondria. Also, it was shown, that doxorubicin inhibits not only the gene HIF-1α expression but its important target genes (PDK-1, TERT, IGF-1) too, while increasing the gene HIF-3α expression in rat cardiomyocytes. These negative effects of doxorubicin impact on the cardiomyocyte contractile activity and the rat cardiohemodynamic. The combined use of doxorubicin and curcumin led to a significant reduction in the free radical processes level and the pro- and antioxidant balance recovery in the mitochondria, significantly improving the functions of the respiratory chain, increasing the K+ entry rate into mitochondria, helping to support mitochondrial membrane potential value and improving the cardi-omyocytes contractile activity.