Liver Damage During Ischemia/Reperfusion and Glutathione: Implications for Potential Organ Donors

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doi:10.1016/j.transproceed.2007.06.001 Copyright © 2007 Elsevier Inc. All rights reserved.

Ischemia reperfusion injury

Liver Damage During Ischemia/Reperfusion and Glutathione: Implications for Potential Organ Donors

M. Vairettia,, A. Ferrignoa, V. Rizzob, P. Richelmia, U. Cillod and R. Imbertic aDepartment of Internal Medicine and Therapeutics, IRCCS Policlinico San Matteo, University of Pavia, Pavia, ItalybDepartment of Biochemistry, IRCCS Policlinico San Matteo, University of Pavia, Pavia, ItalycDepartment of Rianimazione II, IRCCS Policlinico San Matteo, University of Pavia, Pavia, ItalydDepartment I of General Surgery, University of Padua, Padua, Italy. Available online 8 August 2007. Abstract

Free radicals play a central role in the development of liver ischemia/reperfusion (I/R) injury. Reduced glutathione (GSH) is the main hepatic free radical scavenger. Brain-dead patients exhibit abnormalities of endocrine status. Many clinicians administer thyroid hormones to improve the transplantation outcomes. We previously reported that thyroxine (T4) pretreatment decreased rat liver tissue GSH, which was associated with increased liver I/R-induced damage. In this study, we investigated whether the reduction in GSH by T4 pretreatment affected cell viability during anoxia or oxidative stress in suspensions of isolated hepatocytes. Furthermore, we evaluated the levels of GSH in isolated livers from hypothyroid rats preserved at 0−1°C and reperfused. Thyroid hormone modulation was obtained by T4 or 6-propylthiouracil (PTU) treatment. Isolated hepatocytes from T4-pretreated rats that underwent anoxia and oxidative stress, which was induced by tert-butylhydroperoxide, displayed progressive, time-dependent loss of cell viability, which was greater than that in hepatocytes in non–T4-pretreated rats. A significant decrease in GSH levels was observed in isolated hepatocytes obtained from hyperthyroid rats compared with those from euthyroid rats. In contrast, administration of the antithyroid drug PTU increased liver concentrations of GSH at the end of reperfusion thereby improving liver function after cold storage. These results may yield new protective strategies in the management of brain-dead organ donors.

Supported by MIUR-COFIN 2004.Address reprint requests to Dr pia Vairetti, Department Internal Medicine and Therapeutics, University of Pavia, Piazza Botta, 10, 27100 Pavia, Italy.

Transplantation Proceedings Volume 39, Issue 6, July-August 2007, Pages 1768-1770