S. J. Gibbons and P.-J. Verhulst contributed equally to this work and should be considered joint first authors.
Review article: carbon monoxide in gastrointestinal physiology and its potential in therapeutics
Version of Record online: 28 AUG 2013
© 2013 John Wiley & Sons Ltd
Alimentary Pharmacology & Therapeutics
Volume 38, Issue 7, pages 689–702, October 2013
How to Cite
Gibbons, S. J., Verhulst, P.-J., Bharucha, A. and Farrugia, G. (2013), Review article: carbon monoxide in gastrointestinal physiology and its potential in therapeutics. Alimentary Pharmacology & Therapeutics, 38: 689–702. doi: 10.1111/apt.12467
This commissioned review article was subject to full peer-review and the authors received an honorarium from Wiley, on behalf of AP&T.
- Issue online: 3 SEP 2013
- Version of Record online: 28 AUG 2013
- Manuscript Accepted: 7 AUG 2013
- Manuscript Revised: 6 AUG 2013
- Manuscript Revised: 3 MAY 2013
- Manuscript Received: 4 APR 2013
- National Institutes of Health. Grant Numbers: DK57061, DK68055, DK74008
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.
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.
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.
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.
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.