Therapeutic roles of carbon monoxide in intestinal ischemia-reperfusion injury.

Abstract

Intestinal ischemia-reperfusion (I-R) injury is a complex, multifactorial, pathophysiological process with high morbidity and mortality, leading to serious difficulty in treatment. The mechanisms involved in the pathogenesis of intestinal I-R injury have been examined in detail and various therapeutic approaches for intestinal I-R injury have been developed; however, existing circumstances have not yet led to a dramatic change of treatment. Carbon monoxide (CO), one of the by-products of heme degradation by heme oxygenase (HO), is considered as a candidate for treatment of intestinal I-R injury and indeed HO-1-derived endogenous CO and exogenous CO play a pivotal role in protecting the gastrointestinal tract from intestinal I-R injury. Interestingly, anti-inflammatory effects of CO have been elucidated sufficiently in various cell types including endothelial cells, circulating leukocytes, macrophages, lymphocytes, epithelial cells, fibroblast, organ-specific cells, and immune-presenting cells. In this review, we herein focus on the therapeutic roles of CO in intestinal I-R injury and the cell-specific anti-inflammatory effects of CO, clearly demonstrating future therapeutic strategies of CO for treating intestine I-R injury.