Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro antioxidant capacity of sulfasalazine (SASP), its metabolites (SP, 5-ASA), and olsalazine (OAZ), was studied by evaluating their effects on superoxide (O2-.) production. Assay systems were the xanthine-xanthine oxidase (X/XOD) reaction and phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), using the cytochrome c (cyt-c) reduction assay and a luminol-dependent chemiluminescence method. 5-ASA, SASP, and OAZ showed a dose-dependent scavenger effect in both O2-. generating systems, 5-ASA being the most powerful (greater than 50% of inhibition in the PMNs system and greater than 70% in the X/XOD system at 10 microM concentration). SP had an inhibitory effect only in the PMNs system but did not modify the activity of xanthine oxidase, thus excluding a scavenger action. These data suggest that the scavenger effect of 5-ASA, SASP, and OAZ may be an important mechanism of action.
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PMID:Scavenger effect of sulfasalazine, 5-aminosalicylic acid, and olsalazine on superoxide radical generation. 167 Oct 10

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.
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PMID:Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species. 288 49

5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt dihydrate (CAS 80573-04-2, BX661A) is developed as a therapeutic agent for ulcerative colitis. To clarify its mechanism of action, the effects of BX661A and its metabolites 5-aminosalicylic acid (5-ASA) and 4-aminobenzoyl-beta-alanine (4-ABA) on reactive oxygen species: superoxide radicals (O2-) generated by hypoxanthine and xanthine oxidase, hydrogen peroxide (H2O2), hypochlorite radicals (OCl-) and hydroxyl radicals (OH.), were investigated and compared with the effects of 2-hydroxy-5-[[4-[(2-pyridinylamino)sulfonyl]phenyl]azo]-benzoic acid (CAS 599-79-1, salazosulfapyridine, SASP) and its metabolite 4-amino-N-2-pyridinyl-benzenesulfonamide (CAS 144-83-2, sulfapyridine, SP). 1. BX661A, SASP and 5-ASA inhibited O2- radical production in a concentration-dependent manner (IC50 = 0.14, 0.13 and 0.19 mmol/l, respectively). The effects of 4-ABA and SP on O2- radical production were weak (IC50 = > 10 and > 3 mmol/l, respectively). In contrast, superoxide dismutase inhibited O2- radical production in a concentration-dependent manner (IC50 = 1.7 U/ml). 2. BX661A, SASP, 4-ABA and SP had no H2O2 scavenging effects. 5-ASA scavenged H2O2, but its maximal scavenging action was 51.3%. In contrast, catalase scavenged H2O2 in a concentration-dependent manner (IC50 = 0.47 U/ml). 3. BX661A, SASP and 5-ASA scavenged OCl- radicals in a concentration-dependent manner (IC50 = 69.5, 73.8 and 21.7 mumol/l, respectively). 4-ABA and SP had no OCl- radical scavenging effects. In contrast, nordihydroguaiaretic acid (NDGA) scavenged OCl- radicals in a concentration-dependent manner (IC50 = 8.7 mumol/l). 4. BX661A and SASP scavenged OH. radicals in a concentration-dependent manner; the maximal scavenging values were 39.5 (10 mmol/l) and 48.6% (3 mmol/l), respectively. 4-ABA and SP had no OH. radical scavenging effects. In contrast, 5-ASA scavenged OH. radical in a concentration-dependent manner (IC50 = 1.46 mmol/l). These results suggest that BX661A has O2- and OCl- radical scavenging effects and that 5-ASA has O2-, OCl- and OH. radical scavenging effects. Therefore, these effects may be partially involved in the therapeutic effects of BX661A on ulcerative colitis.
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PMID:Effects of BX661A, a new therapeutic agent for ulcerative colitis, on reactive oxygen species in comparison with salazosulfapyridine and its metabolite sulfapyridine. 982 18