Basic Research
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World J Gastroenterol. Feb 14, 2006; 12(6): 908-914
Published online Feb 14, 2006. doi: 10.3748/wjg.v12.i6.908
Trimetazidine: Is it a promising drug for use in steatotic grafts?
Ismail Ben Mosbah, Araní Casillas-Ramírez, Carme Xaus, Anna Serafín, Joan Roselló-Catafau, Carmen Peralta
Ismail Ben Mosbah, Araní Casillas-Ramírez, Carme Xaus, Anna Serafín, Joan Roselló-Catafau, Carmen Peralta, Department of Experimental Pathology; Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas, Instituto de Investigaciones Biomédicas de Barcelona August Pi i Sunyer, Barcelona, Spain
Supported by the Ministerio de Ciencia y Tecnología (project grants HP 2003-0051, BFI 2002-00704 and BFI 2003-00912) and the Agencia Española de Cooperación Internacional (AECI, project grant 25/03/P) (Madrid, Spain
Correspondence to: Dr Joan Roselló-Catafau, Experimental Hepatology Unit, IDIBAPS, C/ Rosellón 161, 7a planta, 08036 Barcelona, Spain. jrcbam@iibb.csic.es
Telephone: +34-933638333 Fax: +34-933638301
Received: July 12, 2005
Revised: July 25, 2005
Accepted: August 3, 2005
Published online: February 14, 2006
Abstract

AIM: Chronic organ-donor shortage has led to the acceptance of steatotic livers for transplantation, despite the higher risk of graft dysfunction or nonfunction associated with the ischemic preservation period of these organs. The present study evaluates the effects of trimetazidine (TMZ) on an isolated perfused liver model.

METHODS: Steatotic and non-steatotic livers were preserved for 24 h in the University of Wisconsin (UW) solution with or without TMZ. Hepatic injury and function (transaminases, bile production and sulfobromophthalein (BSP) clearance) and factors potentially involved in the susceptibility of steatotic livers to ischemia–reperfusion (I/R) injury, including oxidative stress, mitochondrial damage, microcirculatory diseases, and ATP depletion were evaluated.

RESULTS: Steatotic livers preserved in UW solution showed higher transaminase levels, lower bile production and BSP clearance compared with non-steatotic livers. Alterations in perfusion flow rate and vascular resistance, mitochondrial damage, and reduced ATP content were more evident in steatotic livers. TMZ addition to UW solution reduced hepatic injury and ameliorated hepatic functionality in both types of the liver and protected against the mechanisms potentially responsible for the poor tolerance of steatotic livers to I/R.

CONCLUSION: TMZ may constitute a useful approach in fatty liver surgery, limiting the inherent risk of steatotic liver failure following transplantation.

Keywords: Steatotic liver, Ischemia–reperfusion, UW preservation solution