The aim of the present work was to investigate the mechanisms of oxidative damage of rat liver mitochondria in vitro, under hypochlorous acid (HOCl) induced oxidative stress, and in vivo, under acute carbon tetrachloride-induced intoxicationin rats. Hypochlorous acid (50–300 µM), the main inflammatory agent, inhibited liver mitochondria respiratory activityand caused uncoupling in the respiratory and phosporylation processes. The toxic damage of rat liver after 24 h of acute carbon tetrachloride induced intoxication (4 g/kg, intragastrically) was accompanied by a significant reduction in succinate- and glutamate-depen-dent respiration rate in state 3 (by 65%, p< 0.001, and by 50%, p< 0.01, respectively). The respiration control ratio approached 1, reflecting the loss of respirationcontrol. The phosphorylation coefficient significantly decreased due to uncoupling of the oxidation and phosphorylation processes. The mitochondrial alterations were associated with oxidation of intramitochondrial GSH by 25% (p< 0.05), the marked inhibition of succinate dehydrogenase (complex II) by 35% (p< 0.05), and the rise of blood plasma nitric oxide level by 45% (p< 0.05). The impairment of mitochondrial respiratory function may result from the inhibition of enzymatic activities in the respiratory chain and the damage of mitochondrial membrane during intoxication and plays a key role in the development of the CCl4-induced hepatotoxicity. Melatonin administration under CCl4-induced intoxication (three times at a dose of 10 mg/kg)increased the rate of succinate oxidation in state 3 by 30% (p< 0.05) and reversed the increase in glutathione peroxidase activity. Melatonin prevented an elevation of nitric oxide level in the blood plasma of intoxicated animals but did not protect mitochondrial functions under acute intoxication
