Zaouali, Mohamed AmineBen Mosbah, IsmailBoncompagni, EleonoraBen Abdennebi, HassenMitjavila Cors, Maria TeresaBartrons Bach, RamonFreitas, IsabelRimola Castellá, AntonioRoselló Catafau, Juan2022-09-212022-09-2120101007-9327https://hdl.handle.net/2445/189205AIM: 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 anti-ischemic 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 heme-oxygenase-1. CONCLUSION: We found evidence for the role of the HIF-1α/NO system in fatty liver preservation, especially when IGL-1 solution is used.11 p.application/pdfengcc-by-nc (c) Zaouali, Mohamed Amine et al., 2010https://creativecommons.org/licenses/by-nc/4.0/Malalties del fetgeÒxid nítricOxigen en l'organismeConservació d'òrgansLiver diseasesNitric oxideOxygen in the bodyPreservation of organsinfo:eu-repo/semantics/article5893702022-09-21info:eu-repo/semantics/openAccess20653058