Biological oxidants as intestinal secretagogues

Inflammatory bowel disease (IBD) is associated with the release by granulocytes of a variety of oxidants. These oxidants include hydrogen peroxide, hypochlorous acid, superoxide radicals and nitrogen-containing compounds, such as N-chloramines and nitric oxide and its metabolites. In-vivo experiments and clinical observations suggest that some or all of these oxidants may be involved in the pathophysiology of the diarrhoea that is a hallmark symptom of IBD. In vitro, all of these oxidants stimulate to varying degrees small intestinal and/or colonic electrolyte secretion. This chapter will focus principally on the action of monochlolamine (formed from hypochlorous acid and ammonia) and nitric oxide (NO). Evidence is presented to support the idea that these oxidants act through direct and indirect mechanisms in the mucosa to stimulate electrolyte secretion. This may contribute to the accumulation of fluid in the intestine of patients with IBD and contribute to diarrhoea. NO is intriguing because it may physiologically stimulate absorption yet, at higher concentrations, stimulate secretion (as in IBD) and be involved in the diarrhoeagenic action of several laxatives.