Коррекция дисфункции митохондрий печени крыс мелатонином при диабетическом и токсическом поражении

Abstract

Mitochondria play a key role in coordination of the main cellular functions. The aim of the present work was to investigate the mechanisms of oxidative damage of rat liver mitochondria under acute carbon tetrachloride-induced intoxication and diabetes and evaluate correction of mitochondrial dysfunction by melatonin. The toxic damage of rat liver after 24 h of acute carbon tetrachloride-induced intoxication (4 g/kg BW, intragastrically) was accompanied by a decrease in basal respiration rate (by 30%) and a significant reduction in succinate- and glutamate-dependent respiration rate in state 3 (by 65%, p < 0.001, and by 50%, p < 0.01, respectively). The acceptor control ratio and respiration control ratio approached to 1, reflecting the loss of respiration control. The phosphorylation coefficient significantly decreased due to uncoupling of the oxidation and phosphorylation processes. Melatonin administration under CCl4-induced intoxication (three times at doses of 10 mg/kg) was accompanied by a subsequent dissipation of membrane potential and increased the rate of succinate oxidation in state 3 by 30% (p < 0.05). The experimental (30-days) streptozotocin-induced diabetes mellitus caused considerable damage of respiratory activity in rat liver mitochondria. Melatonin administration during diabetes (10 mg/kg BW, 30 days daily) showed a considerable protective effect on the liver mitochondria function, reversing the decreased respiration rate V3 to the control values both for succinate-dependent respiration (p<0.05 in comparison with diabetic animals) and for glutamate-dependent respiration (p<0.01). Similarly, melatonin treatment of diabetic rats reversed the effect of diabetes on the ACR and RCR values both for succinate-dependent respiration and for glutamate-dependent respiration. Melatonin might be considered as effector that regulates mitochondrial function under diabetes and acute intoxication.