Background and objectives: toxic liver injury results in nitrooxidative stress. Melatonin is a\npotent free radical scavenger, an inducible nitric oxide synthase (iNOS) inhibitor and an activator of\nantioxidant enzymes. The aim of this study was to investigate the hepatoprotective effect of exogenous\nmelatonin on animals with acute toxic hepatitis. Material and methods: 36 healthy Sprague-Dawley\nmale rats were split into three equal groups and given carbon tetrachloride (CCl4), 2 g/kg (CCl4 group)\nor the same dose of CCl4 and melatonin, 10 mg/kg (CCl4/melatonin group) or saline (control group).\nThe effect of melatonin on prooxidant and antioxidant system indexes, NO and NOS levels in\nserum and liver, data of mitochondrial chain functions and cytolysis in liver were evaluated in\nall three groups. Results: melatonin significantly decreased activities of AST, ALT, ceruloplasmine\nand thiobarbituric acid reactive substance (TBARS) in serum. Catalase activity was lowered in\nserum but not in the liver. Hepatic TBARS, lipid hydroperoxides and glutathione concentrations\nwere decreased, while superoxide dismutase, mitochondrial cytochrome oxidase and succinate\ndehydrogenase activities increased. Melatonin inhibited synthesis of stable NO metabolites in serum:\nNO2-by 37.9%; NO3-by 29.2%. There was no significant difference in content NO2-in the liver, but\nconcentration of NO3-increased by 32.6%. Melatonin significantly reduced iNOS concentrations both\nin serum (59.7%) and liver (57.8%) but did not affect endothelial isoform enzyme activities neither in\nserum, nor in liver. The histopathological liver lesions observed in the CCl4/melatonin group were\nless severe than those seen in the CCl4 group. Conclusions: we demonstrated an ameliorating effect of\nmelatonin on prooxidants and antioxidants, NO-NOS systems balance, mitochondrial function and\nhistopathological lesions in the liver in rats with CCl4-induced hepatitis.
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