title: Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury.
abstract: The activation of heme oxygenase-1 (HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection. In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload (with signs of a chronic hepatitis) and iron deficiency anemia (with paradoxical increased levels of ferritin). Hypoxia induces HO-1 expression in multiple rodent, bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types (endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury.
authors.affiliation: Clarice Silvia Taemi Origassa, Laboratory of Experimental and Clinical Immunology, Nephrology Division, Medicine Department, Federal University of São Paulo, 04039-032 São Paulo, Brazil.
authors.forename: Clarice Silvia Taemi
authors.initials: CS
authors.lastname: Origassa
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
keywords: Bilirubin; Heme oxygenases; Hepatitis C; Hypoxia; Immunoregulatory; Kupffer cells; Liver ischemia; Polymorphisms