There is a growing body of experimental and clinical evidence to suggest that reactive oxygen metabolites (eg, superoxide, hydrogen peroxide, hydroxyl radical, and halogenated oxidants) may play an important role in the pathogenesis of inflammatory bowel disease (eg, Crohn's disease and ulcerative colitis). Recent studies have demonstrated enhanced production of reactive oxygen species in the chronically inflamed colon. The most likely sources of these oxidants are the phagocytic leukocytes (eg, neutrophils, monocytes, and macrophages), which are known to accumulate within the colonic interstitium during times of active inflammation. Many of these leukocyte-derived oxidants have been shown to mediate cytotoxicity, degrade the extracellular matrix, enhance electrolyte (and water) secretion, alter smooth muscle function, and promote mutagenesis. In addition, the anti-inflammatory effects of 5-aminosalicylic acid, a drug with potent antioxidant activity suggests that oxidants and free radicals may be important mediators of the pathophysiology observed in inflammatory bowel disease. Although there is a large volume of circumstantial evidence that implicates oxy radicals in chronic gut inflammation, there is a relative paucity of published reports that have attempted to directly assess the role of free radicals in models of chronic gut inflammation in vivo. This scarcity of information appears to be due to the lack of long-lived antioxidants with well-characterized mechanisms of action and specific inhibitors of phagocyte-associated reactive oxygen generators. The development of new generation, long-lived antioxidants and specific inhibitors should prove useful in defining a role for reactive oxygen metabolites in inflammatory bowel disease.
Current Opinion in Gastroenterology 1993, 9:971-980