Hepatic Ischemia-Reperfusion Injury: Pathogenesis and Pharmacological Treatment

Abstract

Hepatic ischemia reperfusion injury (R/I) is a hepatic pathophysiologic process occurs post liver transplantation surgery. It also comprises complex systemic process affecting multiple tissues and organs. Hepatic I/R has serious impact on liver function, even producing irreversible failure, which may trigger multiple organ dysfunction. Many factors, including anaerobic metabolism, mitochondrial damage, oxidative stress and secretion of reactive oxygen species (ROS), intracellular calcium overload, cytokines and chemokines produced by Kupffer cells (KCs) and neutrophils are involved in the pathogenesis of hepatic I/R processes. There are many treatment options to combat hepatic I/R injury but none has shown clear beneficial clinical evidence. The purpose of this review is to provide insights into the mechanisms of hepatic I/R injury, indicating the potential factors/signaling pathways involved in this event and available therapeutic approaches that may help to improve controlling hepatic I/R during liver surgery.

Resveratrol promotes liver cell survival in mice liver-induced ischemia-reperfusion through unfolded protein response: a possible approach in liver transplantation

“…Because liver cells are the primary source of multiple metabolic pathways and have a high basal-specific metabolic rate, they are more vulnerable to the exacerbating effects of ischemia, such as hypoxia and ATP depletion [ 4 ]. The destructive effect of I/R stems from generating reactive oxygen species abruptly after re-oxygenation, damaging tissues directly, and triggering a series of destructive cellular reactions, resulting in apoptosis, inflammation, and organ failure [ 5 ]. A deficiency of ATP causes major intracellular organelles to dysfunction and triggers stress responses, e.g., endoplasmic reticulum (ER) stress response [ 6 ].…”