title: Application of heme oxygenase-1, carbon monoxide and biliverdin for the prevention of intestinal ischemia/reperfusion injury.
abstract: Intestinal ischemia/reperfusion (I/R) injury occurs frequently in a variety of clinical settings, including mesenteric artery occlusion, abdominal aneurism surgery, trauma, shock, and small intestinal transplantation, and is associated with substantial morbidity and mortality. Although the exact mechanisms involved in the pathogenesis of intestinal I/R injury have not been fully elucidated, it is generally believed that polymorphonuclear neutrophils, pro-inflammatory cytokines, and mediators generated in the setting of oxidative stress, such as reactive oxygen species (ROS), play important roles. Heme oxygenase (HO) is the rate-limiting enzyme that catalyzes the degradation of heme into equimolar quantities of biliverdin and carbon monoxide (CO), while the central iron is released. An inducible form of HO (HO-1), biliverdin, and CO, have been shown to possess generalized endogenous anti-inflammatory activities and provide protection against intestinal I/R injury. Further, recent observations have demonstrated that exogenous HO-1 expression, as well as exogenously administered CO and biliverdin, have potent cytoprotective effects on intestinal I/R injury as well. Here, we summarize the currently available data regarding the role of the HO system in the prevention intestinal I/R injury.
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
authors.forename: David J
authors.initials: DJ
authors.lastname: Kaczorowski
authors.forename: Ryujiro
authors.initials: R
authors.lastname: Sugimoto
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: McCurry