Review article: Carbon monoxide in gastrointestinal physiology and its potential in therapeutics

Background While carbon monoxide (CO) is a known toxin, it is now recognised that CO is also an important signalling molecule involved in physiology and pathophysiology. Aims To summarise our current understanding of the role of endogenous CO in the regulation of gastrointestinal physiology and pathophysiology, and to potential therapeutic applications of modulating CO. Methods This review is based on a comprehensive search of the Ovid Medline comprehensive database and supplemented by our ongoing studies evaluating the role of CO in gastrointestinal physiology and pathophysiology. Results Carbon monoxide derived from haem oxygenase (HO)-2 is predominantly involved in neuromodulation and in setting the smooth muscle membrane potential, while CO derived from HO-1 has anti-inflammatory and antioxidative properties, which protect gastrointestinal smooth muscle from damage caused by injury or inflammation. Exogenous CO is being explored as a therapeutic agent in a variety of gastrointestinal disorders, including diabetic gastroparesis, post-operative ileus, organ transplantation, inflammatory bowel disease and sepsis. However, identifying the appropriate mechanism for safely delivering CO in humans is a major challenge. Conclusions Carbon monoxide is an important regulator of gastrointestinal function and protects the gastrointestinal tract against noxious injury. CO is a promising therapeutic target in conditions associated with gastrointestinal injury and inflammation. Elucidating the mechanisms by which CO works and developing safe CO delivery mechanisms are necessary to refine therapeutic strategies.