Melatonin protects steatotic and nonsteatotic liver grafts against cold ischemia and reperfusion injury

Mohamed Amine Zaoualí, Russel J. Reiter, Susagna Padrissa-Altés, Eleonora Boncompagni, Joaquín J. García, Hassen Ben Abnennebi, Isabel Freitas, Francisco A. García-Gil, Joan Rosello-Catafau

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Abstract: Chronic organ-donor shortage has required the acceptance of steatotic livers for transplantation purposes despite the higher risk of graft dysfunction or nonfunction associated with the cold ischemia-reperfusion injury. This study evaluated the use of melatonin as an additive to Institute Georges Lopez (IGL-1) solution for protecting nonsteatotic and steatotic liver grafts against cold ischemia-reperfusion injury. In the current investigation, we used an ex vivo isolated perfused rat liver model. Steatotic and nonsteatotic livers were preserved for 24 hr (4°C) in University of Wisconsin or IGL-1 solutions with or without melatonin, as well as in University of Wisconsin solution alone. Thereafter, livers were subjected to 2-hr reperfusion (37°C). We assessed hepatic injury (transaminases) and function [bile production and sulfobromophthalein (BSP) clearance, vascular resistance], as well as other factors potentially implicated in the high vulnerability of steatotic livers against ischemia-reperfusion injury (oxidative stress and related inflammatory mediators including nitric oxide and cytokines). We also evaluated well-known cytoprotective factors as hemeoxygenase 1 (HO-1). Fatty livers preserved in IGL-1 solution enriched with melatonin showed lower transaminase levels and higher bile production and BSP clearance when compared to those obtained for livers maintained in IGL-1 solution alone. A significant diminution of vascular resistance was also observed when melatonin was added to the IGL-1 solution. The melatonin benefits correlated with the generation of nitric oxide (through constitutive e-NOS activation) and the prevention of oxidative stress and inflammatory cytokine release including tumor necrosis factor and adiponectin, respectively. The addition of melatonin to IGL-1 solution improved nonsteatotic and steatotic liver graft preservation, limiting their risk against cold ischemia-reperfusion injury.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalJournal of pineal research
Volume50
Issue number2
DOIs
StatePublished - Mar 1 2011

Keywords

  • IGL-1
  • TNF alpha
  • University of Wisconsin
  • adiponectin
  • cold ischemia-reperfusion injury
  • fatty liver preservation
  • melatonin
  • nitric oxide
  • oxidative stress

ASJC Scopus subject areas

  • Endocrinology

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