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Addition of adenosine monophosphate-activated protein kinase activators to University of Wisconsin solution: a way of protecting rat steatotic livers.
- Source :
-
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society [Liver Transpl] 2007 Mar; Vol. 13 (3), pp. 410-25. - Publication Year :
- 2007
-
Abstract
- 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 degrees C in UW and UW with TMZ and AICAR (separately or in combination) and then perfused ex vivo for 2 hours at 37 degrees 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.<br /> ((c) 2007 AASLD.)
- Subjects :
- AMP-Activated Protein Kinases
Adenine Nucleotides metabolism
Adenosine therapeutic use
Allopurinol therapeutic use
Aminoimidazole Carboxamide therapeutic use
Animals
Glutathione therapeutic use
Insulin therapeutic use
Liver enzymology
Liver physiology
Mitochondria, Liver physiology
Nitric Oxide physiology
Nitric Oxide Synthase metabolism
Oxidative Stress physiology
Raffinose therapeutic use
Rats
Rats, Zucker
Reperfusion Injury prevention & control
Vascular Resistance physiology
Aminoimidazole Carboxamide analogs & derivatives
Enzyme Activators therapeutic use
Fatty Liver prevention & control
Multienzyme Complexes physiology
Organ Preservation Solutions therapeutic use
Protein Serine-Threonine Kinases physiology
Ribonucleotides therapeutic use
Trimetazidine therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1527-6465
- Volume :
- 13
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
- Publication Type :
- Academic Journal
- Accession number :
- 17326058
- Full Text :
- https://doi.org/10.1002/lt.21059