Mucosal injury and gamma-irradiation produce persistent gastric ulcers in the rabbit. Evaluation of antiulcer drug binding to experimental ulcer sites.
A method producing persistent gastric ulcers in the rhesus monkey by combined mucosal injury and gamma-irradiation was modified and evaluated in the rabbit. gamma-Irradiation (800-1000 cGy) immediately after removal of 2-mm-diameter sections of antral mucosa resulted in ulcer craters 5-7 days later. Ulcer sites were characterized by loss of the mucosa, muscularis mucosa, and much of the submucosa. The exposed submucosa was coated with fibrin and necrotic debris infiltrated with heterophils, the rabbit equivalent of neutrophils. These ulcers strongly resemble human chronic gastric ulcers. Binding of Carafate (sucralfate; Marion Laboratories, Inc., Kansas City, MO) and Maalox (magnesia-alumina oral suspension; Wm. H. Rorer, Inc., Ft. Washington, PA) to ulcer and nearby nonulcer sites in the antrum was assessed 1 hour after drug dosing. Drug binding was determined by aluminum quantitation of stomach wall punch biopsies at necropsy. Both drugs significantly increased aluminum bound to the stomach wall compared with vehicle treatment. Significantly more antiulcer drug was bound to ulcer sites than to nearby nonulcer sites only after sucralfate administration. This model of persistent gastric ulcer should be useful to further study gastric ulcer pathogenesis and treatment.
Yokel
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RA
College of Pharmacy, University of Kentucky, Lexington.
Dickey
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KM
D000535:Aluminum / Q000032:analysis; D000536:Aluminum Hydroxide / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000863:Antacids / Q000378:metabolism; D000897:Anti-Ulcer Agents / Q000378:metabolism*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005720:Gamma Rays / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D008276:Magnesium Hydroxide / Q000378:metabolism; D011706:Pyloric Antrum / Q000473:pathology / Q000528:radiation effects; D011817:Rabbits; D013276:Stomach Ulcer / Q000209:etiology* / Q000378:metabolism; D013392:Sucralfate / Q000378:metabolism
D000863:Antacids; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D013392:Sucralfate; D000536:Aluminum Hydroxide; D000535:Aluminum; D008276:Magnesium Hydroxide