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Hypoxia inducible factor-1α accumulation in steatotic liver preservation: Role of nitric oxide

AuthorsZaouali, Mohamed A. ; Mosbah, Ismail Ben ; Rimola, Antoni; Roselló-Catafau, Joan
Issue Date2010
PublisherBaishideng Publishing Group
CitationWorld Journal of Gastroenterology 16(18): 3499-3509 (2010)
Abstract[Aim]: To examine the relevance of hypoxia inducible factor (HIF-1) and nitric oxide (NO) on the preservation of fatty liver against cold ischemia-reperfusion injury (IRI). Methods]: We used an isolated perfused rat liver model and we evaluated HIF-1α in steatotic and non-steatotic livers preserved for 24 h at 4°C in University of Wisconsin and IGL-1 solutions, and then subjected to 2 h of normothermic reperfusion. After normoxic reperfusion, liver enzymes, bile production, bromosulfophthalein clearance, as well as HIF-1α and NO [endothelial NO synthase (eNOS) activity and nitrites/nitrates] were also measured. Other factors associated with the higher susceptibility of steatotic livers to IRI, such as mitochondrial damage and vascular resistance were evaluated. [Results]: A significant increase in HIF-1α was found in steatotic and non-steatotic livers preserved in IGL-1 after cold storage. Livers preserved in IGL-1 showed a significant attenuation of liver injury and improvement in liver function parameters. These benefits were enhanced by the addition of trimetazidine (an antiischemic drug), which induces NO and eNOS activation, to IGL-1 solution. In normoxic reperfusion, the presence of NO favors HIF-1α accumulation, promoting also the activation of other cytoprotective genes, such as hemeoxygenase- 1. [Concluison]: We found evidence for the role of the HIF-1α/NO system in fatty liver preservation, especially when IGL-1 solution is used. © 2010 Baishideng.
DescriptionOpen-Acces journal.-- et al.
Publisher version (URL)http://dx.doi.org/10.3748/wjg.v16.i28.3499
Identifiersdoi: 10.3748/wjg.v16.i28.3499
issn: 1007-9327
e-issn: 2219-2840
Appears in Collections:(IIBB) Artículos
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