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Addition of adenosine monophosphate‐activated protein kinase activators to University of Wisconsin solution: A way of protecting rat steatotic livers
Author(s) -
Ben Mosbah Ismail,
MassipSalcedo Marta,
FernándezMonteiro Izabel,
Xaus Carme,
Bartrons Ramon,
Boillot Olivier,
RosellóCatafau Joan,
Peralta Carmen
Publication year - 2007
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21059
Subject(s) - medicine , adenosine monophosphate , adenosine , protein kinase a , kinase , biochemistry , endocrinology , microbiology and biotechnology , pharmacology , biology
This study investigates how the addition of trimetazidine (TMZ) and aminoimidazole‐4‐carboxamide ribonucleoside (AICAR) to University of Wisconsin (UW) solution protects steatotic livers. Steatotic and nonsteatotic livers were preserved for 24 hours at 4°C in UW and UW with TMZ and AICAR (separately or in combination) and then perfused ex vivo for 2 hours at 37°C. Adenosine monophosphate‐activated protein kinase (AMPK) or nitric oxide (NO) synthesis inhibition in livers preserved in UW with TMZ was also investigated. Hepatic injury and function (transaminases, bile production, and sulfobromophthalein clearance) and factors potentially involved in the susceptibility of steatotic livers to ischemia‐reperfusion (I/R), including vascular resistance, mitochondrial damage, adenosine triphosphate depletion, and oxidative stress were evaluated. AMPK, NO synthase (NOS), nitrate, and nitrite levels were also determined. The addition of TMZ and AICAR (separately or in combination) to UW reduced hepatic injury, improved functionality, and protected against the mechanisms responsible for the vulnerability of steatotic livers to I/R. Like AICAR, TMZ increased AMPK, constitutive NOS, and nitrates and nitrites, and conversely, AMPK or NO synthesis inhibition abolished the benefits of TMZ. In conclusion, TMZ, by means of AMPK, increased NO, thus protecting steatotic livers against their vulnerability to I/R injury. TMZ and AICAR may constitute new additives to UW solution in steatotic liver preservation, whereas a combination of both seems unnecessary. Liver Transpl 13:410–425, 2007. © 2007 AASLD.