A novel method to produce extensive gastric antral ulcer in rats: pharmacological factors involved in the etiology of antral ulceration.
Gastric antral area is the most susceptible region to gastric ulceration in man. However, only limited information is available on animal models. In the present paper, we have developed an improved method for inducing gastric antral ulcers by the administration of 1.0 M HCl after refeeding for 1 h in rats. On day 4, the severe ulcer was found covering extensively the whole area of the antrum, and penetrated through the muscularis mucosae. The incidence of ulceration was 100% and the mean ulcer index was 37.1 +/- 16.6 mm2. In contrast, none of the erosive lesions were observed in the corpus area. Before 24 h, only slight hyperemia was observed in the antral region, suggesting that some submucosal mechanisms are involved in the ulceration processes other than the direct erosive action of HCl on the mucosal surface. Additional treatment with diethyldithiocarbamate (125 mg x kg(-1), s.c.), superoxide dismutase inhibitor, significantly aggravated this antral ulcer, and the ulcer index was 66.0 +/- 13.6 mm2. Allopurinol (50 mg x kg(-1), p.o.) significantly prevented ulcer formation induced by HCl plus DDC. GSH (150 mg x kg(-1), i.p.) also markedly prevented the ulceration. However, DMSO (0.5%, 5 mL x kg(-1), p.o.) was found not to affect ulcer formation. Famotidine (20 mg x kg(-1), p.o.) almost completely inhibited ulcer formation. From the above results, it was concluded that gastric antral ulcer can be induced by the simple treatment of 1.0 M HCl in refed rats, and the antrum has a different defensive mechanism from that in the corpus area. In addition. oxygen derived radicals, especially superoxide anion and endogenous acid secretion were found to be involved in the etiology of the aggravation of the gastric antral ulcer induced by DDC.
Uchida
M
M
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Takayama
M
M
Kato
Y
Y
Tsuchiya
S
S
Horie
S
S
Watanabe
K
K
D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004050:Ditiocarb / Q000633:toxicity; D005753:Gastric Mucosa / Q000473:pathology*; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006851:Hydrochloric Acid / Q000633:toxicity; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology; D011706:Pyloric Antrum; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000473:pathology*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors
D004050:Ditiocarb; D013482:Superoxide Dismutase; D005978:Glutathione; D006851:Hydrochloric Acid; D004121:Dimethyl Sulfoxide