• Esther Carrasco-Chaumel, Joan Roselló-Catafau, Ramon Bartrons, Rosa Franco-Gou, Carme Xaus, Arani Casillas, Emili Gelpí, Joan Rodés, and Carmen Peralta.
• Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas, C/Rosellón 161, 7(a) planta, 08036 Barcelona, Spain.
• J. Hepatol. 2005 Dec 1; 43 (6): 997-1006.

Background/AimsHepatic 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.MethodsSteatotic liver transplantation with or without preconditioning was induced in Zucker rats. The activities of AMPK and NO synthase (NOS) were measured and altered pharmacologically.ResultsPreconditioning 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.ConclusionsThese 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.

36 keywords...

hide…