Melatonin protects against alcoholic liver injury by attenuating oxidative stress, inflammatory response, and apoptosis.

Melatonin is reported to exhibit a wide variety of biological effects, including antioxidant and anti-inflammatory. Previous studies show that melatonin has a protective role in different types of liver injury and fibrosis. But its role in the pathogenesis of alcoholic liver injury remains obscure. The present investigation was designed to determine the effects of melatonin on alcohol-induced hepatic injury in mice. The degree of alcoholic liver injury was evaluated by measuring serum markers and pathological examination. Treatment with melatonin significantly attenuated the increased level of serum aminotransferase, reduced the severe extent of hepatic cell damage, steatosis and the immigration of inflammatory cells, but had no effects on hepatic expression of lipogenic genes. Furthermore, melatonin decreased serum and tissue inflammatory cytokines levels, tissue lipid peroxidation, neutrophil infiltration and inhibited the apoptosis of hepatocytes. Kupffer cells isolated from ethanol-fed mice produced high amounts of reactive oxygen species and tumor necrosis factor alpha, whereas Kupffer cells from melatonin treatment mice produced less reactive oxygen species and tumor necrosis factor alpha compared with model alcohol-feeding mice. These findings suggest that melatonin may represent a novel, protective strategy against alcoholic liver injury by attenuating oxidative stress, inflammatory response and apoptosis.