Superoxide and Post-Ischemic Liver Injury: Potential Therapeutic Target for Liver Transplantation

Ian   N.   Hines; Hirohisa      Harada; Robert      Wolf; Matthew   B.   Grisham

Abstract

Cessation of blood flow to the liver is required during liver transplantation and resectional surgery. A growing body of experimental evidence suggests that restoration of blood flow to the ischemic liver initiates hepatocellular injury which may lead, in some cases, to severe liver injury and graft failure. A large number of studies have implicated reactive oxygen species as potential mediators of post-ischemic tissue injury. Recent developments in genetic engineering as well as chemical modeling, have allowed for the production of novel free radical scavengers including mutated forms of superoxide dismutase (SOD) and low molecular weight SOD mimics with extended circulating half-lives and / or significant membrane permeabilitys. Application of these newly developed free radical scavengers show promising results in animal models of liver I / R and may become powerful tools in the treatment of post-ischemic liver injury that occurs in liver transplantation.

Keywords: transplantation, inflammation, leukocytes, nitric oxide, reactive oxygen species, pro-inflammatory cytokines, nadph oxidase, microvasculature