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

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.

• Authors: 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
• Journal: Journal of pineal research (J Pineal Res) Vol. 50 Issue 2 Pg. 213-21 (Mar 2011) ISSN: 1600-079X [Electronic] England
• PMID: 21108657 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S.

Chemical References

• Nitric Oxide
• Melatonin

Topics

• Animals
• Fatty Liver (drug therapy, metabolism)
• Liver (drug effects, metabolism, pathology)
• Male
• Melatonin (therapeutic use)
• Nitric Oxide (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Zucker
• Reperfusion Injury (prevention & control)