BACKGROUND/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.
BACKGROUND/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.
Authors: Mathilde Steenks; Mark C P M van Baal; Vincent B Nieuwenhuijs; Menno T de Bruijn; Marc Schiesser; Mike H Teo; Tom Callahan; Rob T A Padbury; Greg J Barritt Journal: HPB (Oxford) Date: 2010-05 Impact factor: 3.647
Authors: Sabarinathan Ramachandran; Jane M Liaw; Jianluo Jia; Sean C Glasgow; Wei Liu; Krista Csontos; G A Upadhya; T Mohanakumar; William C Chapman Journal: Transpl Immunol Date: 2012-01-21 Impact factor: 1.708
Authors: Michael J J Chu; Ryash Vather; Anthony J R Hickey; Anthony R J Phillips; Adam S J R Bartlett Journal: HPB (Oxford) Date: 2014-04-09 Impact factor: 3.647
Authors: Mohamed Amine Zaouali; Mohamed Bejaoui; Maria Calvo; Emma Folch-Puy; Eirini Pantazi; Gianfranco Pasut; Antoni Rimola; Hassen Ben Abdennebi; René Adam; Joan Roselló-Catafau Journal: World J Gastroenterol Date: 2014-11-21 Impact factor: 5.742