HIF-1 alpha accumulation in steatotic liver preservation: Role of nitric oxide.

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