Carbon Monoxide: An Essential Signalling Molecule

Carbon monoxide (CO), like nitric oxide (NO), is an essential signalling molecule in humans. It is active in the cardiovascular system as a vasodilator. In addition, CO possesses anti-inflammatory, anti-apoptotic and anti-proliferative properties and protects tissues from hypoxia and reperfusion injury. Some of its applications in animal models include suppression of organ graft rejection and safeguarding the heart during reperfusion after cardiopulmonary bypass surgery. CO also suppresses arteriosclerotic lesions following angioplasty, reverses established pulmonary hypertension and mitigates the development of post-operative ileus in the murine small intestine and the development of cerebral malaria in mice as well as graft-induced intimal hyperplasia in pigs. There have been several clinical trials using air–CO mixtures for the treatment of lung-, heart-, kidney- and abdominal-related diseases. This review examines the research involving the development of classes of compounds (with particular emphasis on metal carbonyls) that release CO, which could be used in clinically relevant conditions. The review is drawn not only from published papers in the chemical literature but also from the extensive biological literature and patents on CO-releasing molecules (CO-RMs).