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Hypoxia inducible factor-1α accumulation in steatotic liver preservation: role of nitric oxide Zaouali, Mohamed Amine Ben Mosbah, Ismail Boncompagni, Eleonora Ben Abdennebi, Hassen Mitjavila Cors, Maria Teresa Bartrons Bach, Ramon Freitas, Isabel Rimola Castellá, Antonio Roselló Catafau, Juan Malalties del fetge Òxid nítric Oxigen en l'organisme Conservació d'òrgans Liver diseases Nitric oxide Oxygen in the body Preservation of organs 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 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. 2022-09-21T16:50:37Z 2022-09-21T16:50:37Z 2010 2022-09-21T16:50:38Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.3748/wjg.v16.i28.3499 World Journal of Gastroenterology, 2010, vol. 16, num. 28, p. 3499-3509 https://doi.org/10.3748/wjg.v16.i28.3499 cc-by-nc (c) Zaouali, Mohamed Amine et al., 2010 https://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess Baishideng Publishing Group Inc Articles publicats en revistes (Ciències Fisiològiques)