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

作者：Kim Seok Joo; Park Jin Gu; Lee Sun Mee^*

来源：Life Sciences, 2012, 90(5-6): 169-176.

DOI：10.1016/j.lfs.2011.10.003

• Alcoholic steatotic liver
• Cold ischemia/reperfusion
• Oxidative stress
• Heme oxygenase-1

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). %26lt;br%26gt;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 degrees C. After 24 h of storage, livers were subjected to 120 min of reperfusion with Krebs-Henseleit bicarbonate buffer at 37 degrees C. Animals were pre-treated with cobalt protoporphyrin (CoPP, 5 mg/kg, i.p.) or zinc protoporphyrin (ZnPP, 25 mg/kg, i.p.), HO-1 inducer and antagonist, respectively. %26lt;br%26gt;Key findings: In the model of ischemia/isolated perfusion, endogenous HO-I 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. %26lt;br%26gt;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.

• 出版日期2012-1-30