Delineation of the protective action of zinc sulfate on ulcerative colitis in rats.
The protective action of zinc compounds in Crohn's disease-like inflammatory bowel disease in animals has been shown. A similar action of zinc sulfate on ulcerative colitis has not been defined. The present study aimed to delineate the protective action of zinc sulfate and the pathogenic mechanisms of 2,4-dinitrobenzene sulfonic acid (DNBS)-induced ulcerative colitis in rats. Zinc sulfate at different concentrations was given either orally (p.o.) or rectally (p.r.) to rats at 42, 48, 66 and 72 h following the induction of colonic inflammation by DNBS. Rats were killed 96 h after instillation of DNBS rectally to assess the severity of colonic damage, myeloperoxidase and xanthine oxidase activities. The involvement of mast cell degranulation and histamine release in the pathogenesis of DNBS-induced colitis was determined by using a mast cell stabilizer (ketotifen) and histamine receptor blockers (terfenadine and ranitidine). DNBS given rectally produced inflammation and ulceration in rats with a pathology resembling ulcerative colitis. Myeloperoxidase activity but not xanthine oxidase activity was sharply increased by this agent. Intrarectal administration of zinc solution and parenteral injection of histamine blockers significantly reduced tissue damage and myeloperoxidase but not xanthine oxidase activity. Ketotifen, a mast cell stabilizer, also significantly decreased mucosal injury and myeloperoxidase activity in the colon. In conclusion, mast cell degranulation followed by histamine release plays an important role in the pathogenesis of DNBS-induced ulcerative colitis. Zinc given rectally has a therapeutic effect against this colitis model, perhaps through the reduction of inflammation and inhibition of the above pathogenic mechanisms.
Luk
Ho H
HH
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 1/F, Li Shu Fan Building, 5 Sassoon Road, Hong Kong, PR China.
Ko
Joshua K S
JK
Fung
Hon S
HS
Cho
Chi H
CH
D000818:Animals; D001557:Benzenesulfonates; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D007665:Ketotifen / Q000627:therapeutic use; D008297:Male; D023421:Models, Animal; D009195:Peroxidase / Q000037:antagonists & inhibitors; D011899:Ranitidine / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016593:Terfenadine / Q000627:therapeutic use; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors; D019287:Zinc Sulfate / Q000627:therapeutic use*
D001557:Benzenesulfonates; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; C001073:2,4-dinitrobenzenesulfonic acid; D019287:Zinc Sulfate; D016593:Terfenadine; D011899:Ranitidine; D009195:Peroxidase; D014969:Xanthine Oxidase; D007665:Ketotifen