title: Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species.
abstract: Ischemia-reperfusion is a major component of injury in vascular occlusion both during liver surgery and during liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms including oxidant stress that contribute to various degrees to the overall organ damage. A large volume of recent research has focused on the use of antioxidants to ameliorate this injury, although results in experimental models have not translated well to the clinic. This review focuses on critical sources and mediators of oxidative stress during hepatic ischemia-reperfusion, the status of current antioxidant interventions, and emerging mechanisms of protection by preconditioning. While recent advances in regulation of antioxidant systems by Nrf2 provide interesting new potential therapeutic targets, an increased focus must be placed on more in-depth mechanistic investigations in hepatic ischemia-reperfusion injury and translational research in order to refine current strategies in disease management.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA. hjaeschke@kumc.edu
authors.forename: Hartmut
authors.initials: H
authors.lastname: Jaeschke
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Woolbright
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis; D005978:Glutathione / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000627:therapeutic use; D006801:Humans; D019194:Ischemic Preconditioning; D007728:Kupffer Cells / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply*; D008930:Mitochondria, Liver / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D006360:Heat-Shock Proteins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D005978:Glutathione