In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg
body weight, single injection) or chronic (1.6g/ kg
body weight, 30 days, biweekly
injections)
carbon tetrachloride - induced intoxication and to evaluate the hepatoprotective potential of the
antioxidant,
melatonin, as well as
succinate and cranberry
flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial
succinate dehydrogenase (complex II) decreased (by 25%, p<0.05). Short-term
melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic
mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial
enzymes,
succinate dehydrogenase and
glutathione peroxidase, as well as that of cytoplasmic
catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CClâ‚„ displayed obvious irreversible impairments. Long-term
melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CClâ‚„, reducing elevated plasma activities of
alanine aminotransferase and
aspartate aminotransferase and
bilirubin concentration, prevented accumulation of
membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of
melatonin (10 mg/kg) plus
succinate (50 mg/kg) plus cranberry
flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage.