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)

Sulfasalazine suppresses mucosal injury in patients with ulcerative colitis, but the mechanism of its therapeutic action is uncertain. In the present study, we examined the mechanism of the protective action of sulfasalazine in a rat model in which colonic epithelial cell loss and subsequent increases in epithelial proliferative activity were induced by intracolonic instillation of sodium deoxycholate. Sulfasalazine or its therapeutically active metabolite 5-aminosalicylic acid suppressed the loss of deoxyribonucleic acid into the colonic lumen and the subsequent increases in mucosal ornithine decarboxylase activity and tritiated thymidine incorporation into deoxyribonucleic acid induced by sodium deoxycholate. Sulfasalazine and 5-aminosalicylic acid also blocked xanthine-xanthine oxidase-induced loss of deoxyribonucleic acid and the subsequent proliferative response. In vitro sodium deoxycholate increased reactive oxygen formation by colonic mucosal scrapings or isolated crypt epithelium. These actions of sodium deoxycholate on reactive oxygen formation were blocked by sulfasalazine or 5-aminosalicylic acid. Sulfapyridine, a therapeutically inactive metabolite of sulfasalazine, had no effect on sodium deoxycholate-induced increases in surface cell sloughing, ornithine decarboxylase, tritiated thymidine incorporation into deoxyribonucleic acid, chemiluminescence, or superoxide production. The ability of sulfasalazine and 5-aminosalicylic acid to scavenge reactive oxygen may play a role in their therapeutic effects of inflammatory bowel disease.
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PMID:Actions of sulfasalazine and 5-aminosalicylic acid as reactive oxygen scavengers in the suppression of bile acid-induced increases in colonic epithelial cell loss and proliferative activity. 288 67

Free radicals and reactive oxygen metabolites have been implicated as important pathologic mediators in many clinical disorders and diseases. An efficient method of detecting the free radical scavenger effect is through xanthine oxidase (XO) inhibition. The inhibition efficiency on XO has been detected as the rate of uric acid production, which has max 295 nm. Sulfasalazine showed potent inhibiting activity on XO (IC50 = 25.11 microM; Ki = 50.88 microM) and induced a mixed-type (non-competitive-uncompetitive) inhibition of the substrate xanthine. 2-mercapto-4(3H)-quinazolinone (16) and 2-mercaptopyrimidine (4) displayed inhibiting activity on XO with IC50 = 98.71 and 136.14 microM, while apparent inhibition constants (Ki) were 158.38 and 62.46 microM, respectively. However benzotriazoles showed weak inhibitory effect. The spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) by electron spin resonance (ESR) detected the presence of O2-* and OH*. It showed that the percentage inhibition for formation of DMPO-OOH for 2-mercapto-pyrimidine and sulfasalazine were 64.78 and 35.09, but for hydroxylation were 49.51, 38.55, 37.29 for 2-mercapto-4(3H)-quinazolinone, sulfasalazine and 2-mercaptopyrimidine at 500 microM, respectively.
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PMID:Reactive oxygen scavenger effect of pyrimidines, benzotriazoles and related compounds. 1201 75