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Title

Adenosine monophosphate-activated protein kinase and nitric oxide in rat steatotic liver transplantation

AuthorsCarrasco-Chaumel, Esther; Roselló-Catafau, Joan ; Bartrons, Ramón; Franco-Gou, Rosa ; Xaus, Carme ; Casillas, Arani; Gelpí, Emili ; Rodés, Joan; Peralta, Carmen
KeywordsPreconditioning
Reperfusion
Peroxynitrite
Oxidative stress
Fatty liver
Cold ischemia
Issue DateDec-2005
PublisherElsevier
CitationJournal of Hepatology 43(6): 997-1006 (2005)
AbstractBackground/Aims: Hepatic steatosis is a risk factor for transplantation. We examined the role of AMP-activated protein kinase (AMPK) and nitric oxide (NO) in the benefits of preconditioning in steatotic liver transplantation. Methods: Steatotic liver transplantation with or without preconditioning was induced in Zucker rats. The activities of AMPK and NO synthase (NOS) were measured and altered pharmacologically. Results: Preconditioning or AMPK activation with aminoimidazole-4-carboxamide ribonucleoside (AICAR) increased AMPK and constitutive NOS activities and protected against lipid peroxidation, nitrotyrosine formation and hepatic injury in both grafts. Inhibition of AMPK activity removed the benefits of preconditioning. NO synthesis inhibition abolished the benefits of preconditioning or AICAR. Therefore, preconditioning or AICAR, through AMPK activation, may induce NO synthesis, thus protecting against hepatic injury in both steatotic and non-steatotic liver transplantation. In non-steatotic grafts, NO donors simulated the benefits of preconditioning. However, in steatotic grafts, NO supplementation was ineffective. Conclusions: These results indicate (a) a potential relationship between AMPK and NO in the benefits of preconditioning in steatotic liver transplantation, (b) AICAR as a new phamacological strategy in steatotic liver transplantation and (c) a differential effect of NO supplementation in both grafts. © 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Publisher version (URL)http://dx.doi.org/10.1016/j.jhep.2005.05.021
URIhttp://hdl.handle.net/10261/114005
DOI10.1016/j.jhep.2005.05.021
Identifiersdoi: 10.1016/j.jhep.2005.05.021
issn: 0168-8278
Appears in Collections:(IIBB) Artículos
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