Hypoxia inducible factor-1alpha accumulation in steatotic liver preservation: role of nitric oxide.

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-1alpha in steatotic and non-steatotic livers preserved for 24 h at 4 degrees 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-1alpha 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-1alpha 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-1alpha accumulation, promoting also the activation of other cytoprotective genes, such as heme-oxygenase-1.

CONCLUSION:

We found evidence for the role of the HIF-1alpha/NO system in fatty liver preservation, especially when IGL-1 solution is used.

• Authors: Mohamed Amine Zaouali, Ismail Ben Mosbah, Eleonora Boncompagni, Hassen Ben Abdennebi, Maria Teresa Mitjavila, Ramon Bartrons, Isabel Freitas, Antoni Rimola, Joan Roselló-Catafau
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 16 Issue 28 Pg. 3499-509 (Jul 28 2010) ISSN: 2219-2840 [Electronic] United States
• PMID: 20653058 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• IGL-1 solution
• Organ Preservation Solutions
• Nitric Oxide
• Nitric Oxide Synthase Type III
• Heme Oxygenase-1
• Glutamate Dehydrogenase

Topics

• Animals
• Cold Ischemia
• Disease Models, Animal
• Fatty Liver (metabolism)
• Glutamate Dehydrogenase (metabolism)
• Heme Oxygenase-1 (metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Liver (blood supply, drug effects, metabolism)
• Liver Transplantation
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Organ Preservation Solutions (pharmacology)
• Rats
• Rats, Zucker
• Reperfusion Injury (metabolism, prevention & control)