16-16-dimethylprostaglandin-e and Stomach-Ulcer

This study compares the gastroprotective effects of colloidal bismuth subcitrate (De-Nol) with those of sucralfate and a methylated analogue of prostaglandin E2 (PGE2) against acute gastric lesions induced by acidified aspirin and absolute ethanol in rats. Both De-Nol and sucralfate given orally prevented dose dependently the formation of gastric lesions by these ulcerogens, De-Nol being, respectively, twice and seven times more potent, on a weight basis, than sucralfate. As the gastroprotective activities of both De-Nol and sucralfate on ethanol lesions can be reversed by pretreatment with indomethacin and as De-Nol and sucralfate increase the mucosal generation and luminal release of PGE2, we postulate that mucosal prostaglandins may be involved in the mechanism of action of these drugs on the gastric mucosa.

Topics: Animals; Aspirin; Dinoprostone; Ethanol; Gastric Juice; Gastric Mucosa; Organometallic Compounds; Prostaglandins E; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Stomach Ulcer; Sucralfate

The effect of 16,16-dimethyl prostaglandin E2 (DmPGE2), in doses subthreshold for antisecretory activity, were examined in female rats. The aims were to determine if DmPGE2 alters the disposition of acetylsalicylic acid (ASA) within the gastric mucosa and if DmPGE2 could attenuate the ulcerogenic effect of oral ASA. Gastric lesions occurred after an oral, but not an intravenous dose of 150 mg/kg ASA. Lesions could be prevented by pretreatment with 5 micrograms/kg DmPGE2 orally 30 min prior to ASA. DmPGE2 elevated fundic concentrations of both ASA and salicylic acid (SA) within the first hour when ASA was given orally. The ratio of the concentration of ASA/SA in fundus was not changed, indicating that DmPGE2 did not depress the fundic esterase activity. It is concluded that the cytoprotective effect of DmPGE2 is not related to a change in mucosal concentration or elimination of ASA or SA.

Topics: Administration, Oral; Animals; Aspirin; Chromatography, High Pressure Liquid; Female; Gastric Mucosa; Injections, Intravenous; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Stomach Ulcer

Duodenal ulcers were produced in rats following either an oral or parenteral administration of 200 mg/kg of mepirizole, a nonsteroidal antiinflammatory agent. Deep ulcers, including perforated ones, were induced in the proximal duodenum with an incidence of over 90%. Mortality due to perforation was less than 5%. The agent also induced several erosions in the antrum. Feeding of animals after the ingestion of mepirizole markedly suppressed the development of both duodenal ulcers and gastric erosions. Antacids, anticholinergic agents, a histamine H2-receptor antagonist and 16-DMPGE2 dose-dependently inhibited mepirizole-induced duodenal ulcers. Gastric erosions were also significantly inhibited by antacids and anticholinergic agents but not by a histamine H2-receptor antagonist and 16-DMPGE2. Intraduodenally administered mepirizole dose-dependently inhibited the gastric secretion in pylorus-ligated rats. This ulcer model should be useful for screening antiulcer agents and for the study of pathogenesis of duodenal ulcers and gastric erosions.

Topics: Administration, Oral; Animals; Antacids; Chemical Phenomena; Chemistry; Dose-Response Relationship, Drug; Duodenal Ulcer; Epirizole; Gastric Acidity Determination; Histamine H2 Antagonists; Humans; In Vitro Techniques; Infusions, Parenteral; Male; Models, Biological; Parasympatholytics; Prostaglandins E, Synthetic; Pyrazoles; Rats; Stomach Ulcer

Acute erosions of the stomach may occur in association with human spinal cord injuries. Erosion of the glandular portion of the stomach also occurs after cervical cord transection in the rat. Reports on the effects of antacids and cimetidine in the prevention of acute "stress" erosions in animals and humans have shown conflicting results. A prostaglandin analog, 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) has been shown to prevent gastric erosions in rats produced by nonsteroid antiinflammatory compounds. Cimetidine 50 mg/kg (intraperitoneal), 16,16-dmPGE2 10 micrograms/kg (intraperitoneal), and antacid 2 ml (intragastric) were individually given to groups of spinal rats at 0 and 4 hr. 16,16-dmPGE2 and antacid both resulted in significant reduction in mean ulcer length compared to controls after 8 hr (P less than 0.05) whereas cimetidine showed no significant effect, even though cimetidine caused a significant decrease in gastric acid output compared to both 16,16-dmPGE2 and controls (P less than 0.01). It is concluded that cimetidine on this dosage schedule is not effective in the prevention of gastric erosions in a cervical cord section rat model, whereas the ulceroprotective effects of 16,16-dmPGE2 and antacids are significant. It is suggested that the gastric mucosal cells remain vulnerable to injury in the cimetidine-treated spinal rat due to secretory inhibition, but are protected by buffering action of antacids or by "cytoprotective" effects of prostaglandin.

Topics: Acute Disease; Animals; Antacids; Anti-Inflammatory Agents; Cimetidine; Gastric Acidity Determination; Gastric Mucosa; Guanidines; Injections, Intraperitoneal; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains; Spinal Cord Injuries; Stomach Ulcer