The production of an amine-modified derivative of 5-aminosalicylic acid by activated neutrophils. Roles for myeloperoxidase and chloride ions.
Following incubation with activated neutrophils, two metabolites of 5-aminosalicyclic acid (5-ASA) were identified by HPLC. These two metabolites accounted for approximately 60% and 20% of the original 5-ASA. The formation of the major metabolite was prevented by pre-incubation with the peroxidase inhibitor, azide, and reduced by the omission of chloride ions from the incubation medium, or the presence of catalase. A similar product was generated by sodium hypochlorite or myeloperoxidase/H2O2, mass spectroscopical analysis being consistent with it being 5-nitroso-salicylate. Our finding suggests that the efficacy of 5-ASA results from its ability to react with and so scavenge hypochlorite ions. The amount of amine-modified 5-ASA in the faecal stream may thus provide an indicator for hypochlorite production in the bowel.
Laffafian
I
I
University Department of Surgery and Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Brown
R C
RC
Hallett
M B
MB
D000636:Aminosalicylic Acids / Q000378:metabolism*; D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D013058:Mass Spectrometry; D019804:Mesalamine; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D012459:Salicylates / Q000378:metabolism*
D000636:Aminosalicylic Acids; D002712:Chlorides; D012459:Salicylates; C071881:5-nitroso-salicylate; D019804:Mesalamine; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase