Melatonin Protective Effects against Liver Ischemia/Reperfusion Injury

Hepatic ischemiareperfusion (I/R) is a common phenomenon during liver surgery, transplantation, infection and trauma which results in damage and necrosis of the hepatic tissue through different pathways. Mechanisms involved in I/R damage are very intricate and cover several aspects. Several factors are involved in I/Rinduced damages; briefly, decrease in sinusoidal perfusion and ATP generation because of low or no O2 supply, increase in production of reactive oxygen species (ROS) and inflammatory factors and destruction of parenchymal cells resulted by these molecules are of the main causes of liver tissue injury during reperfusion. Melatonin amp;rsquo;s antioxidant effect, and regulatory roles in the expression of different genes in the I/R insulted liver have been investigated by several studies. Melatonin and its metabolites are of the powerful direct scavengers of free radicals and ROS, so it can directly protect liver cell impairment from oxidative stress following I/R. In addition, this bioactive molecule upregulates antioxidant enzyme genes like superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT). Tumor necrosis factors (TNF amp;alpha;) and interleukin1 (IL1), as potent proinflammatory factors, are generated in huge amounts during reperfusion. Melatonin is able to alleviate TNF amp;alpha; generation and has hepatoprotective effect during I/R. It reduces the production of proinflammatory cytokines and chemokines via reducing the binding of NF amp;kappa;B to DNA. Imbalance between vasodilators (nitric oxide, NO) and vasoconstrictors (endothelin, ET) during I/R was shown to be the primary cause of liver microcirculation disturbance. Melatonin helps maintaining the stability of liver circulation and reduces hepatic injury during I/R through preventing alteration of the normal balance between ET and NO. The aim of this review was to explore the mechanisms of liver I/R injuries and the protective effects of melatonin against them.