Dorothea Aures

Topical Aspirin Plus HCl Gastric Lesions in the Rat: Cytoprotective Effect of Prostaglandin, Cimetidine, and Probanthine

The effect of representative agents of three classes of antisecretory compounds; prostaglandins, histamine H2-receptor antagonist, and anticholinergic agents, on acute gastric mucosal lesions produced by topical aspirin (200 mg/kg) plus HCl (150 mM) in the pylorus-ligated rat was studied. Acid was given exogenously so as to negate any antisecretory effect of the drugs studied. Both nonantisecretory and antisecretory doses of each agent as determined by preliminary secretory studies were employed. The postaglandin analogue 16,16-dimethyl prostaglandin E2, the H2-receptor antagonist cimetidine, and the anticholinergic agent probanthine, in both doses studied, all significantly reduced lesion formation. The H1-receptor antagonist mepyramine neither protected by itself nor enhanced the protective effect of cimetidine. Pepsin release into the gastric content increased with increasing mucosal damage. However, addition of pepsin to the gastric instillate had no effect on severity lesions in any group, which indicates that the increased pepsin was the result of, and not the cause of, the mucosal damage. The findings indicate that all three classes of antisecretory agents studied are also cytoprotective, i.e., they can protect against gastric mucosal injury by topical aspirin plus HCl by some mechanism other than inhibition of acid and pepsin secretion.

Epidermal growth factor stimulates ornithine decarboxylase activity in the digestive tract of mouse.

Summary This study examined the effect of EGF (6 μg g-1 body wt, subcutaneously) on OD concentration in stomach, duodenum, midgut and colon, as well as a control tissue, heart, in 8-day-old mice. The animals were killed 4 hr after either EGF or control water injections. OD activity, expressed as picomoles of 14CO2 liberated from 1-[14C]l-ornithine per mg wet weight tissue, was significantly higher in the animals given EGF than in controls in the stomach (EGF 29.9 ± 6.8; control 9.9 ± 3.6, P < .05) and the duodenum (EGF 51.7 ± 16.9; control 6.5 ± 4.3, P < .05) but not in the midgut, colon or heart. It is concluded that epidermal growth factor stimulated ornithine decarboxylase activity in the stomach and duodenum of neonatal mice suggesting a possible role for EGF (or urogastrone) in mucosal repair and defense in these tissues.

Comparison of Intravenous and Intragastric Aspirin in Production of Antral Gastric Ulcers in Cats

Abstract In cats receiving continuous intravenous infusion of histamine dihydrochloride (160 μg kg-1 hr-1; 40 mg kg-1 of aspirin was given as a bolus injection either intravenously or intragastrically. When the animals were killed either 1 or 4 hr later, all cats in both groups had ulcers of the antral part of the stomach extending through the mucosa. The mean area occupied by the ulcers was not significantly different in the two groups. Plasma and mucosal salicylate concentrations at the end of the study were not significantly different in the two groups. We conclude that, in cats receiving an intravenous infusion of histamine, intravenous and intragastric aspirin are equally effective in producing antral gastric ulcers.

Effect of increased gastric mucosal histamine on alcohol-induced gastric damage in rats.

The aim of this study was to determine whether the cytoprotective effect of prostaglandin might be mediated, at least in part, by inhibition of intramucosal histamine release. Intragastric instillation of increasing concentrations of ethanol in 150 mM HCl resulted in increasing lesion scores and increasing histamine release into the gastric content. Pretreatment with 16,16-dimethyl prostaglandin E2 significantly reduced both lesion scores and gastric histamine output. The intragastric instillation of histamine with tracer [14C]histamine either with or after 50% ethanol resulted in significant gastric tissue uptake of histamine and increased acid secretion. However this had no effect on lesion score, protein output or the protective effect of prostaglandin pretreatment. We conclude that the cytoprotective effect of 16,16-dimethyl prostaglandin E2 in the rat is independent of intramucosal histamine release.

Mechanism of Prevention of Aspirin-Induced Gastric Lesions by Bile Duct Ligation in the Rat

UNLABELLED Gastric reflux of bile has been reported to be essential for the production of acute gastric mucosal lesions by intragastric aspirin in the rat. The purpose of the present study was to determine whether bile duct legation of pylorus ligation in the rat inhibits asprin-induced gastric lesions, and, if so, what the protective mechanisms are. Operations were performed under ether anesthesia. Asprin, 200 mg per kg, was instilled into the stomach 1/2 hr postsurgery (bile duct ligation or pylorus ligation). Four hours later the rats were killed, the stomachs were examined, and mucosal lesions were scored. Bile duct ligation, but not pylorus ligation, significantly protected against aspirin-induced gastric-lesions. Bile duct ligation, in pylorus-ligated rats, inhibited gastric acid output by 78%. Instilling HCl + aspirin in bile duct-ligated rats restored lesion formation. Shunting bile to the colon (to prevent bile reflux) did not prevent aspirin lesions. Salicylate determination, to ascertain whether bile duct ligation altered asprin absorption, revealed no significant differences between bile duct ligation and aspirin, shunt + aspirin, and sham shunt + aspirin in plasma and gastric tissue salicylate concentrations. CONCLUSIONS (1) Bile duct legation protects against aspirin-induced gastric mucosal lesions by inhibiting gastric HCl secretion. As a corollary, a certain amount of acid in the stomach is necessary for aspirin-induced gastric lesions to form. (2) Bile reflux is not necessary for aspirn-induced gastric lesions in the rat.