Ischemia-reperfusion injury (IRI) is increased after transplantation of steatotic livers. Since those livers are increasingly used for transplantation, protective strategies must be developed. Reactive oxygen species (ROS) play a key role in hepatic IRI. In lean organs, glutathione (GSH) is an efficient scavenger of ROS, diminishing IRI. The aim of this study was to evaluate whether GSH also protects steatotic allografts from IRI following transplantation. Fatty or lean livers were explanted from 10-week-old obese or lean Zucker rats and preserved (obese 4 h, lean 24 h) in hypothermic University of Wisconsin solution. Arterialized liver transplantation was then performed in lean syngeneic Zucker rats. Recipients of fatty livers were treated with GSH (200 mu mol/h/kg) or saline during reperfusion (2 h, n = 5). Parameters of hepatocellular damage and bile flow were measured. Transplantation of steatotic livers enhanced early reperfusion injury compared to lean organs as measured by increased aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase plasma levels. Bile flow was also reduced in steatotic grafts. Intravenous administration of GSH effectively decreased liver damage in fatty allografts and resulted in improved bile flow. Intravenous application of GSH effectively reduces early IRI in steatotic allografts and improves recovery of these marginal donor organs following transplantation. Copyright (C) 2010 S. Karger AG, Basel