Oxidative stress in hepatic ischemia-reperfusion injury: the role of antioxidants and iron chelating compounds.
Ischemia-reperfusion (IR) injury is a multifactorial process triggered when the liver or other organs are transiently subjected to reduced blood supply followed by reperfusion. It has been shown that "reactive oxygen species" (ROS) are generated during ischemia and reperfusion and may represent pivotal mediators of the ensuing pathological complications. In some cases, however, moderate production of ROS may exert protective effects, a phenomenon presumably related to "ischemic preconditioning". This review will focus mainly on: a) describing the sources and the biochemical mechanisms of ROS generation during ischemia and reperfusion, b) discussing current developments in understanding the biochemical pathways by which ROS may induce toxic or protective effects, c) critically evaluating the results of previous attempts to counteract the toxic effects of ROS by using a variety of antioxidant and transition metal-chelating agents, and d) if feasible, proposing potential new pharmaceutical agents aimed at ameliorating ROS-inducing deleterious effects during reperfusion. It is concluded that ROS are generated from different sources, at different periods during IR, and may act by a variety of not well understood biochemical mechanisms which ultimately lead to cell damage and tissue failure.
Galaris
D
D
Laboratory of Biological Chemistry, University of Ioannina Medical School, 451 10 Ioannina, Greece. dgalaris@cc.uoi.gr
Barbouti
A
A
Korantzopoulos
P
P
D000818:Animals; D000975:Antioxidants / Q000502:physiology / Q000627:therapeutic use*; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*
D000975:Antioxidants; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species