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.
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.
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects; D005260:Female; D005609:Free Radicals; D019804:Mesalamine; D009955:Ornithine Decarboxylase / Q000032:analysis; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013427:Sulfapyridine / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D019820:Xanthine; D014970:Xanthines / Q000494:pharmacology
D000636:Aminosalicylic Acids; D005609:Free Radicals; D014970:Xanthines; D003840:Deoxycholic Acid; D019820:Xanthine; D012460:Sulfasalazine; D019804:Mesalamine; D004247:DNA; D013482:Superoxide Dismutase; D009955:Ornithine Decarboxylase; D010100:Oxygen; D013936:Thymidine; D013427:Sulfapyridine