Protective effects of resveratrol and melatonin on carbon tetrachloride induced liver injury

The aim of this study was to investigate the protective effects ofbresveratrol and melatonin against carbon tetrachloride (CCl4) induced hepatic injury, using biochemical and histological parameters.Carbon tetrachloride, a xenobiotic commonly used in the generation of experimental nonalcoholic fatty liver disease. The principle causes of ccl4 induced hepatic damage is lipid peroxidation in cell and organel memranes and decreased activities of antioxidant enzymes and generation of free radicals.Melatonin is mainly secreted by the pineal gland, plays an important role in various physiological processes, including the regulation of circadian and endocrine rhythms, stimulation of immune functions. Also, melatonin is a well- known antioxidant and free radical scavenger.Resveratrol is a polyphenolic compound and found of high concentration in the skin and seeds of grapes, berries and peanuts. Its well- known cytoprotective, antioxidant and antiinflammatory effects. On the otherhand, it provides inhibition of kupffer cells and adhesion molecules. Previously, it was suggested that resveratrol stimulated nitric oxide production in endothelial cells, has a vasodilatory effect on blood vessels.In this study total eighty male Wistar albino rats (150- 180 g) were divided ten groups.Group 1: Control. 0.9% NaCl, 1ml/kg/dayGroup 2: Olive oil. 1ml/kg/dayGroup 3: CCl4. 1ml/kg/day (dissolved in olive oil)Group 4: Resveratrol. 10mg/ kg/dayGroup 5: Melatonin. 20mg/kg/dayGroup 6: Control. 0.9% NaCl, 1ml/kg/dayGroup 7: Olive oil. 1ml/kg/dayGroup 8: CCl4. 1ml/kg/day (dissolved in olive oil)Group 9: Resveratrol. 10mg/ kg/dayGroup 10: Melatonin. 20mg/kg/dayFirst five groups were given for 4 days, last five groups were given for 20 days intraperitoneally (i.p). The rats in five groups 5.day of experiment, in last five groups 21.day of experimentwere sacrificed. After intracardiac blood was taken,livers were removed. The liver tissue samples were processed by routine tissue processed for light and electron microscopic examination.The liver sections of the acute and cronic CCl4 groups showed histologic alterations such as vacuolation, apoptotic badies, intracelluler oedema, mitochondria and endoplasmic reticulum injury in hepatocities. Furthermore, inflammatory cell infiltration, necrosis and fibrosis were observed.The groups treated with melatonin and resveratrol were observed significantly improvement in histological parameters of liver damage induced by carbon tetrachloride.As a result, we conclude that melatonin and resveratrol treatments show beneficial effects on CCl4- induced liver steatosis and damage in rats.