The oxygen-centered radicals scavenging activity of sulfasalazine and its metabolites. A direct protection of the bowel.
Oxygen-centered radicals, such as superoxide (O2-) and hydroxyl radicals (.OH) generated by phagocytes have been suggested to be involved in the pathogenesis of chronic inflammations of the bowel, such as Crohn's disease and colitis ulcerosa. Recently, sulfasalazine (SASP) and its metabolites have been reported to exert their effects as a direct scavenger of oxygen-centered radicals in the bowel. To scavenge oxygen-centered radicals in vivo, however, SASP and its metabolites have to react with O2- and/or .OH in vitro very rapidly, furthermore they have to reach an appropriate (possible millimolar) concentration range at the site of inflammation. To test this possibility, we investigated the direct O2- and .OH scavenging activity of SASP and its metabolites using the specific electron paramagnetic resonance/spin trapping method, and we compared the 50% inhibition rates of SASP and its metabolites with their known concentrations in the bowel and in the human plasma. It was found that SASP and its metabolites, such as 5-amino-salicylic acid (5-ASA), and acetyl-5-amino-salicylic acid (AC-5-ASA), but not sulfapyridine (SP) and acetyl-sulfapyridine (Ac-SP) have a direct O2- and .OH scavenging activity in vitro systems. Among the compounds, SASP and 5-ASA can reach a concentration which is appropriate to scavenge oxygen-centered radicals in the bowel but not in the human plasma. It was concluded that the in vivo antiinflammatory effects of SASP and its metabolites are, at least partly, due to the direct oxygen-centered scavenging activity of these drugs.
2nd Department of Medicine, Semmelweis University Medical School, Budapest, Hungary.
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L
Prónai
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Yukinobu
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Láng
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J
Fehér
D016166:Free Radical Scavengers; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D010101:Oxygen Consumption / Q000187:drug effects*; D013113:Spin Labels; D012460:Sulfasalazine / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D016166:Free Radical Scavengers; D013113:Spin Labels; D013481:Superoxides; D017665:Hydroxyl Radical; D012460:Sulfasalazine