Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jul 28, 2010; 16(28): 3499-3509
Published online Jul 28, 2010. doi: 10.3748/wjg.v16.i28.3499
Hypoxia inducible factor-1α accumulation in steatotic liver preservation: Role of nitric oxide
Mohamed Amine Zaouali, Ismail Ben Mosbah, Eleonora Boncompagni, Hassen Ben Abdennebi, Maria Teresa Mitjavila, Ramon Bartrons, Isabel Freitas, Antoni Rimola, Joan Roselló-Catafau
Mohamed Amine Zaouali, Ismail Ben Mosbah, Joan Roselló-Catafau, Experimental Hepatic Ischemia Reperfusion Unit, Institut of Biomedical Research of Barcelona, Spanish National Research Council, 08036, Barcelona, Spain
Mohamed Amine Zaouali, Antoni Rimola, Joan Roselló-Catafau, Liver Transplantation and Graft Viability Unit, August Pi i Sunyer Biomedical Research Institut, 08036, Barcelona, Spain
Hassen Ben Abdennebi, Laboratory of Human Physiology, Faculty of Pharmacy, University of Monastir, 5000, Monastir, Tunisia
Eleonora Boncompagni, Isabel Freitas, Animal Biology Department, Pavia University, 27100, Pavia, Italy
Maria Teresa Mitjavila, Department of Physiology, Faculty of Biology, University of Barcelona, 08028, Barcelona, Spain
Ramon Bartrons, Physiological Sciences Department, Bellvitge Campus, Institut of Biomedical Research of Bellvitge-Barcelona University, 08907, Barcelona, Spain
Antoni Rimola, Joan Roselló-Catafau, CIBER-EHD, Instituto de Salud Carlos III, 08036, Barcelona, Spain
Author contributions: Zaouali MA, Ben Mosbah I and Boncompagni E carried out the experimental work; Zaouali MA, Ben Abdennebi H, Mitjavila MT and Bartrons R provided protocols and analyzed data; Ben Abdennebi H, Freitas I and Rimola A established the animal experimental model used in this study and contributed to the critical analyses of the data; Zaouali MA and Roselló-Catafau J designed the study, coordinate the experiments and wrote the paper.
Supported by The Ministerio de de Sanidad y Consumo (PI 081988), CIBER-EHD, Instituto Carlos III, Madrid and Ministerio de Asuntos Exteriores y de Cooperación Internacionales (A/020255/08 and A/02987/09), Madrid
Correspondence to: Dr. Joan Roselló-Catafau, Experimental Hepatic Ischemia Reperfusion Unit, Institut of Biomedical Research of Barcelona, Spanish National Research Council, C/ Rosselló 161, 7th floor, E-08036-Barcelona, Spain. jrcbam@iibb.csic.es
Telephone: +34-93-3638333 Fax: +34-93-3638301
Received: January 14, 2010
Revised: February 16, 2010
Accepted: February 23, 2010
Published online: July 28, 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 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.

Keywords: Fatty liver; Tissue preservation; Hypoxia inducible factor-1α; IGL-1; Nitric oxide; Trimetazidine