Role of accumulated gastric content in the pathogenesis of cysteamine- and mepirizole-induced duodenal ulcers in the rat.
Subcutaneous administration of cysteamine and mepirizole (at ulcerogenic and non- or weakly ulcerogenic doses) to fasted rats induced villous damage to the duodenum within 4 h. Only the damage induced by ulcerogenic doses progressed to macroscopically visible ulcers 10-12 h later. A considerable increase in gastric content was observed for more than 6-8 h after administration of the ulcerogenic dose of agents, but normal contents were noted 12 h later. The intraduodenal pH remained low for up to 16-20 h when ulcerogenic doses were given, but returned to control levels within 8-12 h when non-ulcerogenic doses were given. Histamine similarly caused villous damage to the duodenum, yet there was no progression to an ulcer. Accumulation of gastric contents and a lower intraduodenal pH with histamine persisted for only 2 h and 1 h, respectively. We conclude that prolonged accumulation of gastric contents for up to 8 h together with a decreased lower intraduodenal pH for 16-20 h are necessary for the developmental progression of villous damage to well-defined ulcers in the presence of ulcerogens.
Tanaka
H
H
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Takeuchi
K
K
Okabe
S
S
D000137:Acid-Base Imbalance / Q000503:physiopathology; D000818:Animals; D003543:Cysteamine; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004840:Epirizole; D005746:Gastric Emptying / Q000502:physiology*; D006632:Histamine; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D004840:Epirizole; D003543:Cysteamine; D006632:Histamine