Melatonin and its protective role in attenuating warm or cold hepatic ischaemia/reperfusion injury

Abstract

Although the liver is the only organ with regenerative capacity, various injury factors induce irreversible liver dysfunction and end-stage liver disease. Liver resection and liver transplantation (LT) are effective treatments for individuals with liver failure, liver cirrhosis and liver cancers. The remnant or transplanted liver tissues will undergo hepatic ischaemia/reperfusion (IR), which leads to oxidative stress, inflammation, immune injury and liver damage. Moreover, systemic ischaemia induced by trauma, stroke, myocardial ischaemia, haemorrhagic shock and other injury factors also induces liver ischaemia/reperfusion injury (IRI) in individuals. Hepatic IRI can be divided into warm IRI, which is induced by liver surgery and systemic ischaemia, and cold IRI, which is induced by LT. Multiple studies have shown that melatonin (MT) acts as an endogenous free radical scavenger with antioxidant capacity and is also able to attenuate hepatic IRI via its anti-inflammatory and antiapoptotic capacities. In this review, we discuss the potential mechanisms and current strategies of MT administration in liver surgery for protecting against warm or cold hepatic IRI. We highlight strategies to improve the efficacy and safety of MT for attenuating hepatic IRI in different conditions. After the potential mechanisms underlying the interactions between MT and other important cellular processes during hepatic IR are clarified, more opportunities will be available to use MT to treat liver diseases in the future.

Keywords: inflammation; injury; ischaemia/reperfusion; liver; melatonin; mitochondria.

FIGURE 1

Hepatic ischaemia/reperfusion results in liver injury via activation of mitochondrial reactive oxygen species (ROS), inflammation and immune responses

FIGURE 2

Melatonin (MT) and its metabolites protect against hepatic IRI by directly or indirectly inhibiting oxidative stress, inflammation and immune responses

FIGURE 3

Addition of melatonin (MT) to the preservation solution or administration of MT to liver donors significantly improves liver function and inhibits graft rejection in liver transplantation