EFFECTS OF BX661A, A NEW THERAPEUTIC AGENT FOR ULCERATIVE-COLITIS, ONREACTIVE OXYGEN SPECIES IN COMPARISON WITH SALAZOSULFAPYRIDINE AND ITS METABOLITE SULFAPYRIDINE

Citation
I. Kimura et al., EFFECTS OF BX661A, A NEW THERAPEUTIC AGENT FOR ULCERATIVE-COLITIS, ONREACTIVE OXYGEN SPECIES IN COMPARISON WITH SALAZOSULFAPYRIDINE AND ITS METABOLITE SULFAPYRIDINE, Arzneimittel-Forschung, 48(10), 1998, pp. 1007-1011
Citations number
17
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy","Chemistry Medicinal",Chemistry
Journal title
ISSN journal
0004-4172
Volume
48
Issue
10
Year of publication
1998
Pages
1007 - 1011
Database
ISI
SICI code
0004-4172(1998)48:10<1007:EOBANT>2.0.ZU;2-J
Abstract
5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt d ihydrate (CAS 8057304-2, BX661A) is developed as a therapeutic agent f or ulcerative colitis. To clarify its mechanism of action, the effects of BX661A and its metabolites 5-aminosalicylic acid (5-ASA) and 4-ami nobenzoyl-beta-alanine (4-ABA) on reactive oxygen species: superoxide radicals (O-2(-)) generated by hypoxanthine and xanthine oxidase, hydr ogen peroxide (H2O2), hypochlorite radicals (OCl-) and hydroxyl radica ls (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-pyridi nyl-benzenesulfonamide (CAS 144-83-2, sulfapyridine, SP). 1. BX661A, S ASP and 5-ASA inhibited O-2(-) radical production in a concentration-d ependent manner (IC50 = 0.14, 0.13 and 0.19 mmol/l, respectively). The effects of 4-ABA and SP on O-2(-) radical production were weak (IC50 = > 10 and > 3 mmol/l, respectively). In contrast, superoxide dismutas e inhibited O-2(-) radical production in a concentration-dependent man ner (IC50 = 1.7 U/ml). 2. BX661A, SASP, 4-ABA and SP had no H2O2 scave nging effects. 5-ASA scavenged H2O2, but its maximal scavenging action was 51.3%. In contrast, catalase scavenged H2O2 in a concentration-de pendent 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 mu mol/l, respectively). 4-ABA and SP had no OCl- radical sca venging effects. In contrast, nordihydroguaiaretic acid (NDGA) scaveng ed OCl- radicals in a concentration-dependent manner (IC50 = 8.7 mu mo l/l). 4. BX661A and SASP scavenged OH. radicals in a concentration-dep endent 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 scave nging effects. In contrast, 5-ASA scavenged OH. radical in a concentra tion-dependent manner (IC50 = 1.46 mmol/l). These results suggest that BX661A has O-2(-) and OCl- radical scavenging effects and that 5-ASA has O-2(-), OCl- and OH. radical scavenging effects. Therefore, these effects may be partially involved in the therapeutic effects of BX661A on ulcerative colitis.