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Effects of gastric distension and prostaglandin on acid ethanol-induced mucosal lesions in the rat
Authors:Koji Takeuchi PhD  Hideyuki Nishiwaki  Nobuyuki Hara  Susumu Okabe PhD
Affiliation:(1) Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, 607 Kyoto, Japan
Abstract:
The effects of gastric distension on the morphology of acidified ethanol (AE) -induced mucosal lesions and on the protective action of 16,16-dm PGE2 were investigated in rats. AE (50% ethanol in 150 mM HCl) was given by gavage in the intact stomach or through a fistula prepared in the forestomach in the pylorus-ligated stomach. AE produced elongated bands of hemorrhagic necrosis within 1 hr in the former, while in the pylorus-ligated stomach the shape of lesions varied depending upon the volume of irritant. One milliliter produced bandlike lesions, whereas 2 ml or more induced widespread lesions; such volumes were observed to remove the mucosal folds. 16,16-dm PGE2 (0.3–10 mgrg/kg, subcutaneous) dose dependently reduced bandlike lesions in the intact stomach, but had no or little effect on non-band-like lesions in the pylorus-ligated stomach. This agent (10 mgrg/kg) had a slight effect on the reduction of PD caused by 10-min exposure of the stomach to AE (2 ml) in the intact stomach, while such effects were not apparent in the pylorus-ligated stomach. Oral gentian violet (2 ml, 0.3% w/v) produced bandlike staining of the mucosa in intact rats, but the effect was blocked by pyloric ligation. 16,16-dm PGE2 also significantly prevented the localized staining pattern seen in intact rats. These results suggest that (1) the bandlike pattern of AE-induced injury is dependent on the presence of mucosal folds (distending the stomach abolishes mucosal folds and widespread injury results); (2) 16,16-dm PGE2 prevented the fold-related, bandlike lesions and bandlike staining of the mucosa, but failed to abolish the generalized lesions; and (3) PG cytoprotection appears associated with the formation of bandlike lesions which are dependent on the presence of mucosal folds.
Keywords:ethanol  gastric lesions  gastric distension  prostaglandin  mucosal fold  cytoprotection
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