The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury.

Abstract

Hepatic ischemia-reperfusion injury is a major cause of post-operative hepatic dysfunction and liver failure after transplantation. This review summarizes the mechanisms of ischemia-reperfusion injury and analyzes the protective strategies based on the recent developments in the field. Development of hepatic ischemia-reperfusion injury is associated with metabolic acidosis, calcium overloading, and changes of mitochondrial membrane permeability. Hypoxia-induced activation of Kupffer cells results in generation of reactive oxygen species (ROS). These processes lead to activation of inflammation and immune responses that involve multiple cells and signaling molecules and result in increased level of apoptosis and necrosis. Generation of ROS is one of the major risk factors in the hepatic ischemia-reperfusion injury. A number of methods aimed to reduce the oxidative stress have been investigated, and some of them have been applied clinically. The methods mainly rely on the activation of pro-survival genes and associated mechanisms capable of reducing the level of ROS and inflammation at pre-treatment and post-conditioning stages. Potential benefits of these clinical approaches have been discussed here.