Carbon monoxide: a new pharmaceutical agent?

Abstract

Small amounts of carbon monoxide (CO) are continuously produced in mammals. The intracellular levels of this gaseous molecule can markedly increase under stressful conditions following the induction of heme oxygenases (HO), ubiquitous enzymes responsible for the catabolism of heme. The development of a technology concerning the CO-releasing molecules (CO-RMs) that control the delivery and action of CO under different pathological conditions represents a major step forward in the development of CO-based pharmaceuticals with therapeutic applications. CO is important for the homeostatic control of cardiovascular functions. Abnormal metabolism and function of CO contribute to the pathogenesis and development of hypertension. Another vascular disease in which the role of CO has been evaluated is pulmonary arterial hypertension. Important results have been reported in which CO prevents intimal hyperplasia by arresting hyperproliferative vascular smooth muscle cells as well as increased mobilization and recruitment of bone-marrow-derived progenitor cells. Transplantation has been a field of research, in which most studies have investigated the beneficial properties of CO-RMs. CO gas and CO-RMs have produced promising results in the preservation of organs for transplantation. The anti-inflammatory properties of CO and CO-RMs have been demonstrated in a multitude of animal models of inflammation, suggesting a possible therapeutic application for inflammatory diseases. Despite therapeutic benefit in animal model studies, the efficacy of CO in humans remains unclear. Further studies are expected to better understand the pharmacokinetics as well as long- and short-term effects of CO-RMs.