Influence of Diazoxide on the Function of Mitochondria in Guinea Pig Liver under Myocardium Dystrophy

Effects of ATP-sensitive potassium (КATP) channel opener diazoxide (1 mg/kg) and inhibitor 5-hydroxydecanoate (5 mg/kg) on ADP-induced mitochondrial respiration by Chance under adrenaline myocardium dystrophy were studied. The process of lipid peroxidation in the liver also was investigated. Substrates of oxidation, such as 0.35 mМ succinate and 1 mМ α-ketoglutarate, were used. To define the role of NADHand FADH-dependent substrates in mitochondrial respiratory chain oxidation, inhibitory analysis with: rotenone (10 μM) – the inhibitor of complex І of the electron transport chain, and malonic acid (2 mM) – the inhibitor of succinate dehydrogenase.was additionally done. The results indicated that the adrenaline myocardium dystrophy is accompanied by activation of succinate oxidation. Simultaneously decrease in the mitochondrial rate of respiration and efficiency of oxidative phosphorylation by αketoglutarate oxidation was noted. Moreover, evident activation of free radicals reactions was observed. Treatment with diazoxide under adrenaline myocardium dystrophy caused elevation of the efficiency of oxidative processes functioning with simultaneous decrease in intensity of lipid peroxidation process in blood and liver. These changes accompanied increase in α-ketoglutarate oxidation efficiency with a temporary decrease in lipid peroxidation process, which reduced the negative effect of catecholamine on the mitochondrial function. Previously mentioned effects were blocked by the treatment with 5-hydroxydecanoate which is a selective mitochondrial KATP channel inhibitor.