The Role of Prostaglandins in Liver Ischemia-Reperfusion Injury

M.   A.   Hossain; H.      Wakabayashi; K.      Izuishi; K.      Okano; S.      Yachida; H.      Maeta

doi:10.2174/138161206777947678

Abstract

Ischemia reperfusion (IR) of the liver is a multifactorial process that, at least in part, is responsible for the morbidity associated with major liver surgery under occlusion of the portal triad with the Pringle maneuver, total vascular exclusion or after liver transplantation. Surgeons are confronted with IR injury (IRI) more often than they anticipate. Although the human body has its own defense system, understanding the pathophysiology of IRI is essential for the surgeon in preventing and/or treating the reperfusion injury in common clinical practice. Several endogenous mechanisms exist to overcome IRI and a large number of pharmacological agents have also been found to confer protection against ischemic injury in the liver. They either blocked the injurious pathways directly or they subjected the liver to preconditioning. Prostaglandins (PGs) are a group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase (COX) pathway. They are short-lived, hormone-like chemicals that regulate cellular activities on a moment-to-moment basis and are produced in most tissues of the body, although the liver has emerged as the major organ participating in the synthesis, degradation and elimination of arachidonate products of systemic origin. PGs are released through the prostaglandin transporter on the cells plasma membrane. During the last decade intensive work on the cytoprotective effects of PGs on livers suffering from IRI have been well documented. Prostaglandins confer their protective effects on IR-injured livers mainly by inhibiting the generation of reactive oxygen species, preventing leukocyte migration, reducing the synthesis or production of membrane degradation products, improving hepatic insulin and lipid metabolism, and regulating the production of inflammatory cytokines and cell adhesion molecules. Production of PGs have been found essential also soon after partial hepatectomy for hepatocyte proliferation. Liver, ischemia reperfusion and prostaglandins are intimately related; their interaction remains to be fully understood. The present review highlights the accumulation of recent advances in this topic.

Keywords: Liver, ischemia, reperfusion, mechanism, cellular-interactions, Kupffer cell, neutrophils, prostaglandins