The reaction of 5-amino-salicylic acid with hypochlorite. Implications for its mode of action in inflammatory bowel disease

Abstract

Although 5-amino-salicylic acid (5-ASA) provides effective treatment for inflammatory bowel disease, its mode of action is unestablished. 5-ASA inhibits luminol-dependent chemiluminescence triggered by activated neutrophils, hydrogen peroxide plus peroxidase or sodium hypochlorite. The concentrations required for 50% inhibition of the cells was approximately 3.6 microM. In the non-cellular system, the concentration of 5-ASA required for total inhibition being approximately equivalent to concentration of sodium hypochlorite. The reaction of 5-ASA with hypochlorite or activated neutrophils resulted in the production of a non-fluorescent product of 5-ASA. The production of this metabolite by cells was dependent upon the activity of the peroxidase and occurred with a time course which was coincident with oxygen consumption. It was concluded that by reacting with hypochlorite, 5-ASA would provide protection against the potentially damaging effects of activated neutrophils in the inflamed bowel.