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Protective effect of heme oxygenase-1 induction against hepatic injury in alcoholic steatotic liver exposed to cold ischemia/reperfusion
- 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.
- Subjects :
- Male
medicine.medical_specialty
Liquid diet
Portal venous pressure
Protoporphyrins
General Biochemistry, Genetics and Molecular Biology
Rats, Sprague-Dawley
Lipid peroxidation
chemistry.chemical_compound
Internal medicine
Lactate dehydrogenase
medicine
Animals
Enzyme Inhibitors
Hyaluronic Acid
General Pharmacology, Toxicology and Pharmaceutics
Ethanol
L-Lactate Dehydrogenase
Cold Ischemia
Zinc protoporphyrin
Fatty liver
Organ Preservation
General Medicine
medicine.disease
Glutathione
Portal Pressure
COPP
Liver Transplantation
Rats
Heme oxygenase
Endocrinology
Liver
chemistry
Biochemistry
Enzyme Induction
Reperfusion Injury
Lipid Peroxidation
Heme Oxygenase-1
Fatty Liver, Alcoholic
Subjects
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