Heme oxygenase-1 induction in hepatocytes and non-parenchymal cells protects against liver injury during endotoxemia
AffiliationDepartment of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
Liver Research Institute, University of Arizona, 1501 N. Campbell Avenue, Tucson, Arizona 85724, USA
Department of Pathology, University of Texas Health Science Center, Houston, Texas 77030, USA
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CitationComparative Hepatology 2004, 3(Suppl 1):S42 http://www.comparative-hepatology.com/content/3/S1/S42
Rights© Dorman et al; licensee BioMed Central Ltd 2004.
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AbstractINTRODUCTION:Heme oxygenase-1 (HO-1) is a stress response enzyme, which catalyses the breakdown of heme into biliverdin-IX alpha, carbon monoxide and ferrous iron. Under situations of oxidative stress, heat stress, ischemia/reperfusion injury or endotoxemia, HO-1 has been shown to be induced and to elicit a protective effect. The mechanism of how this protective effect is executed is unknown.RESULTS:HO-1 induction with cobalt protoporphorin (Co-PP) dose-dependently protected against apoptotic cell death as well as neutrophil-mediated oncosis in the galactosamine/endotoxin (Gal/ET) shock model. Induction of HO-1 with Co-PP dose-dependently protected against neutrophil-mediated oncosis as indicated by attenuated ALT release and TNF-mediated apoptotic cell death as indicated by reduced caspase-3 activation. HO-1 induction did not attenuate Gal/ET-induced TNF-alpha formation. Furthermore, a similar protective effect with the high dose of Co-PP was observed when animals were treated with Gal/TNF-alpha.CONCLUSIONS:HO-1 induction attenuates apoptosis and neutrophil-mediated oncosis in the Gal/ET shock model. However, the protective effect is not due to the reduction of TNF-alpha release or the attenuation of neutrophil accumulation in the liver sinusoids.
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