“…Recent years have witnessed a steady increase in interest in the signaling roles and therapeutic effects of CO. , Studies in animal models have demonstrated the promise of using CO for treating inflammation of various types, sickle cell disease, cancer, and cancer metastasis . CO has also been shown to offer cytoprotection and organ protection, − play an important role in neuromodulation and cognition via a possible CO–dopamine–heme oxygenase signaling axis, and regulate the circadian clock, which is further implicated in an array of pathophysiological and pharmacological events . Despite all the success in demonstrating the pharmacological effects of CO in cell culture and in animal models, there are also many unanswered questions, including issues of sufficiency of the heme supply to allow CO a role in rapid signaling, the molecular mechanisms(s) of action, , and safety.…”