5-Aminosalicylate: oxidation by activated leukocytes and protection of cultured cells from oxidative damage.
It has been postulated that oxygen radicals may play a role in the pathogenesis of inflammatory bowel disease. If so, then a drug like 5-aminosalicylate (5-ASA), which is used to treat such diseases, might work by interacting with oxygen-derived species. We found that activated mononuclear cells and activated granulocytes, as well as the products of the Fenton reaction, transformed [14C]5-ASA to a number of metabolites, among which we have characterized salicylate and gentisate. We also found that the lethal effect on cultured Chinese hamster ovary cells of adding either superoxide radical or hydrogen peroxide, components of the respiratory burst of activated white blood cells, was diminished by the addition of 100 micrograms/ml (0.65 mM) of 5-ASA. Thus, we have demonstrated that 5-ASA was oxidized by the oxidative burst of white blood cells and that 5-ASA protected cells from damage by oxygen-derived species, two findings which may offer an explanation for the role of 5-ASA in the treatment of inflammatory bowel disease.
D000636:Aminosalicylic Acids / Q000097:blood*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005609:Free Radicals; D005841:Gentisates; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D062385:Hydroxybenzoates / Q000097:blood; D007962:Leukocytes / Q000378:metabolism*; D008213:Lymphocyte Activation; D019804:Mesalamine; D010053:Ovary / Q000378:metabolism; D010084:Oxidation-Reduction; D012459:Salicylates / Q000097:blood; D020156:Salicylic Acid; D013481:Superoxides / Q000633:toxicity
D000636:Aminosalicylic Acids; D005609:Free Radicals; D005841:Gentisates; D062385:Hydroxybenzoates; D012459:Salicylates; D013481:Superoxides; C039316:potassium superoxide; D019804:Mesalamine; D006861:Hydrogen Peroxide; D020156:Salicylic Acid; C010925:2,5-dihydroxybenzoic acid