| Autor: |
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 |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Journal of pineal research. 50(2) |
| ISSN: |
1600-079X |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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