The reaction of 5-amino-salicylic acid with hypochlorite. Implications for its mode of action in inflammatory bowel disease.
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.
Williams
J G
JG
University Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Hallett
M B
MB
D000636:Aminosalicylic Acids / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D005453:Fluorescence; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism* / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008163:Luminescent Measurements; D019804:Mesalamine; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism
D000636:Aminosalicylic Acids; D019804:Mesalamine; D006997:Hypochlorous Acid