Use of carbon monoxide as a therapeutic agent: promises and challenges.

As a by-product of heme catabolism by the heme oxygenase system, carbon monoxide (CO) has been neglected for many years, and only recently has its role as an essential signaling molecule been appreciated. In the past decade, the use of CO gas in pre-clinical experimental models of disease has produced some remarkable data indicating that its therapeutic delivery to mammals could alleviate inflammatory processes and cardiovascular disorders. However, the inherent toxic nature of CO cannot be ignored, knowing that inhalation of uncontrolled amounts of this gas can ultimately lead to serious systemic complications and neuronal derangements. From a clinical perspective, a key question is whether a safe and therapeutically effective threshold of CO can be reached locally in organs and tissues without delivering potentially toxic amounts through the lung. The advent of CO-releasing molecules (CO-RMs), a group of compounds capable of carrying and liberating controlled quantities of CO in cellular systems, appears a plausible alternative in the attempt to overcome the limitations of CO gas. Although in its infancy and far from being used for clinical applications, the CO-RMs technology is supported by very encouraging biological results and reflected by the chemical versatility of these compounds and their endless potential to be transformed into CO-based pharmaceuticals.