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Protective effect of heme oxygenase-1 induction against hepatic injury in alcoholic steatotic liver exposed to cold ischemia/reperfusion

Authors :
Sun-Mee Lee
Jin Gu Park
Seok-Joo Kim
Source :
Life Sciences. 90:169-176
Publication Year :
2012
Publisher :
Elsevier BV, 2012.

Abstract

Aims The purpose of this study was to investigate the cytoprotective role of heme oxygenase-1 (HO-1) induction in hepatic injury in alcoholic steatotic liver exposed to cold ischemia/reperfusion (I/R). Main methods Animals were fed an ethanol liquid diet or isocaloric control diet for 5 weeks. Isolated perfused rat livers were preserved in Histidine–Tryptophan–Ketoglutarate at 4 °C. After 24 h of storage, livers were subjected to 120 min of reperfusion with Krebs–Henseleit bicarbonate buffer at 37 °C. Animals were pretreated with cobalt protoporphyrin (CoPP, 5 mg/kg, i.p.) or zinc protoporphyrin (ZnPP, 25 mg/kg, i.p.), HO-1 inducer and antagonist, respectively. Key findings In the model of ischemia/isolated perfusion, endogenous HO-1 was downregulated in the livers fed with ethanol diet (ED I/R). In ED I/R group, portal pressure and lactate dehydrogenase release were significantly increased, while bile output and hyaluronic acid clearance decreased compared to rats fed on control diet (CD I/R). Furthermore, hepatic glutathione content decreased and lipid peroxidation increased in the ED I/R group compared to the CD I/R group. These alterations were attenuated by upregulation of HO-1 with CoPP pretreatment. Significance Our results suggest that chronic ethanol consumption aggravates hepatic injury during cold I/R and it is likely due to downregulation of endogenous HO-1. Prior induction of HO-1 expression may provide a new strategy to protect livers against hepatic I/R injury or to increase the donor transplant pool through modulation of marginal alcoholic steatotic livers.

Details

ISSN :
00243205
Volume :
90
Database :
OpenAIRE
Journal :
Life Sciences
Accession number :
edsair.doi.dedup.....638bcdfd22b4ddaacb9db17c66cd5b53
Full Text :
https://doi.org/10.1016/j.lfs.2011.10.003