Summary
There is a growing body of experimental data to suggest that the chronically inflamed intestine and/or colon may be subjected to considerable oxidative stress. The most probable sources of these oxidants are the phagocytic leukocytes since these cells are known to be present in large numbers in the inflamed mucosa and are known to produce significant amounts of reactive oxygen species in response to certain inflammatory stimuli. Because the colonic mucosa contains relatively small amounts of antioxidant enzymes (e.g. SOD, catalase, GSH peroxidase) it is possible that the gut mucosa may be overwhelmed during times of active inflammation which could result in intestinal injury. If reactive oxygen species play an important role in mediating mucosal injury in IBD then it should be possible to attenuate this injury by the use of antioxidants. One such drug is the sulfasalazine metabolite 5-ASA. It may not be coincidence that this potent antiinflammatory metabolite is a potent antioxidant that possesses multiple mechanisms of action including nitrogen, carbon and oxygen-centered free radical scavenging properties as well as the ability to decompose HOCl and scavenge hemoprotein-associated oxidants. In addition 5-ASA has the additional property of being able to chelate iron and render it poorly redox active. The reason that 5-ASA is so effective in vivo may be due to this multitude of antioxidant properties. This would also suggest that other, more potent antioxidants may prove beneficial in the treatment of IBD.
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Abbreviations
- SAZ:
-
sulfasalazine
- 5-ASA:
-
5-aminosalicylic acid
- IBD:
-
inflammatory bowel disease
- SOD:
-
superoxide dismutase
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Dr. Yamada is on leave from the First Department of Internal Medicine, Nagoya City University Medical School, Nagoya, Aichi, Japan
This work supported by grants from the NIH (DK39168), the Crohn's and Colitis Foundation of America and Pharmacia-LEO Therapeutics
Manuscripts published in this issue were the matter of a Symposium held at the University of Ulm, April 24–27, 1991
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Yamada, T., Grisham, M.B. Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation. Klin Wochenschr 69, 988–994 (1991). https://doi.org/10.1007/BF01645144
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DOI: https://doi.org/10.1007/BF01645144