Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species.
The relative in vitro anti-oxidant efficacy of sulphasalazine (salicylazosulphapyridine, SASP) and its metabolites (5-aminosalicylic acid, 5-ASA; sulphapyridine, SP) was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leucocytes (PMNs) and a cell free, xanthine-xanthine oxidase system. Salicylazosulphapyridine, 5-ASA, and SP showed anti-oxidant effects to the various degrees. In particular, production of OH, which is one of the most potent reactive oxygen species, was remarkably suppressed by 5-ASA dose relatedly. These findings suggest that SASP and its metabolites play an important role in the inhibition of respiratory bursts. As the potent products of the respiratory burst by polymorphonuclear leucocytes are thought to be important inflammatory mediators, suppression of toxic reactive oxygen species generation by these agents may partly explain the therapeutic efficacy of SASP in ulcerative colitis, which is characterised by an acute mucosal inflammation dominated by polymorphonuclear leucocytes accumulation.
D000328:Adult; D000636:Aminosalicylic Acids / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002474:Cell-Free System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D019804:Mesalamine; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013427:Sulfapyridine / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism; D015054:Zymosan
D000636:Aminosalicylic Acids; D000975:Antioxidants; D014970:Xanthines; D013481:Superoxides; D012460:Sulfasalazine; D019804:Mesalamine; D015054:Zymosan; D014969:Xanthine Oxidase; D013427:Sulfapyridine