Misoprostol preclinical pharmacology

Bauer, R. F.

doi:10.1007/bf01309396

Cited by 58 publications

(21 citation statements)

References 11 publications

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“…Decrease in gastric acid secretion is thought to occur by inhibition of histamine-sensitive adenylate c y c l a~e .~~.~' The cytoprotective effect is not completely understood but is thought to be due to stimulation of bicarbonate and mucus secretion, increased mucosal blood flow, decreased vascular permeability, or increased cellular proliferation and migration.1°. 13 In a recent study of human patients, misoprostol was more effective in preventing NSAID-induced gastrointestinal injury than H2-receptor antagonists of similar antisecretory ability.31 This finding supports a cytoprotective effect of misoprostol beyond its antisecretory effects.…”

Section: Discussionsupporting

confidence: 67%

The Effect of Misoprostol on Aspirin‐Induced Gastroduodenal Lesions in Dogs

Johnston

Leib

Forrester

et al. 1995

Veterinary Internal Medicne

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Misoprostol, a synthetic prostaglandin El analog, is effective in treating and preventing nonsteroidal antiinflammatory drug (NSAI D)-induced gastrointestinal lesions in humans. The effectiveness of misoprostol in preventing aspirin-induced gastroduodenal injury was studied in 3 groups of 6 adult mixed breed dogs. Group I received 3 Fg/ kg misoprostol PO tid. Group II received 3 pg/kg misoprosto1 PO tid and 35 mg/kg aspirin PO tid. Group Ill received 35 mg/kg aspirin PO tid. Endoscopy was performed on days 0, 5, 14, and 30. Five regions of the upper gastrointestinal tract were qualitatively scored from 1 to 1 2 based on the presence of submucosal hemorrhage, erosion, or ulceration, with ulceration receiving a higher numerical score than submucosal hemorrhage. A total score was assigned based on the sum of the scores from all regions.onsteroidal antiinflammatory drugs (NSAIDs) N are frequently used for treating degenerative joint disease. Side effects of NSAID therapy in the dog include gastrointestinal bleeding and ulceration, and inhibition of platelet Aspirin causes gastrointestinal damage in a dose-dependent fashion and has been shown to cause gastrointestinal bleeding in dogs at the clinically recommended dose of 25 to 35 mg/kg.3-5 The prevalence of serious gastrointestinal complications (ulceration with perforation, severe bleeding) for dogs is unknown, but is estimated at 1 per 5,500 in humans treated with NSAIDs for longer than 1 month.6 More than 10% of human patients receiving NSAIDs chronically have an ulcer at any given The mechanism of aspirin-induced gastrointestinal damage is controversial, but is thought to

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Section: Discussionsupporting

confidence: 67%

The Effect of Misoprostol on Aspirin‐Induced Gastroduodenal Lesions in Dogs

Johnston

Leib

Forrester

et al. 1995

Veterinary Internal Medicne

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“…First, mucosal lesions were elicited by administering an excess amount of HC1 together with ethanol directly into the gastric lumen, in order to minimize the possible involvement of omeprazole-mediated antisecretory ef fects. Second, the protective action of omeprazole could be mimicked by the prostaglandin analogue misoprostol, but not by the Hi-blocker ranitidine, although both these drugs are endowed with significant inhibitory activity on acid secretion [13,22], In line with these findings, other drugs exerting gastric acid antisecretory effects, such as cimetidine and atropine, failed to prevent the ethanolinduced mucosal damage in rats [21,23]. Third, when gastric acid secretion was evaluated in pylorus-ligated rats, the antisecretory effects of omeprazole, misoprostol and ranitidine showed a very poor correlation with their respective actions on ethanol-HCl-induced mucosal inju ry.…”

Section: Correlation Analysismentioning

confidence: 99%

“…route 30 min before the induction of gastric mucosal damage. Doses of omeprazole, misoprostol and ranitidine were selected on the basis of previous studies dealing with gastroprotection against necrotizing agents in rats [8,13,14].…”

Section: Animals and Drug Treatmentmentioning

confidence: 99%

Mechanisms of Protection by Omeprazole against Experimental Gastric Mucosal Damage in Rats

et al. 1995

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In the present study, the protective effect of omeprazole on gastric mucosa injury induced by ethanol •HCl in rats and the putative mechanisms involved in this action were investigated. Misoprostol and ranitidine were used as reference drugs. The morphometric analysis of histological sections showed that omeprazole caused a significant reduction of mucosal necrotic damage, this effect being associated with a marked increase in Alcian blue recovery from gastric bound mucus. In addition, omeprazole elicited a significant inhibition of gastric acid secretion from pylorus-ligated rats. Misoprostol exerted similar effects to those obtained with omeprazole, even if the Alcian blue recovery and the acid output were affected to a lesser extent. By contrast, ranitidine failed to influence both the mucosal damage and the Alcian blue recovery, while it exerted a marked inhibition on acid secretion. The present results indicate that omeprazole is effective in protecting gastric mucosa from necrotic damage induced by ethanol •HCl and suggest that an enhancement of gastric mucus barrier may account for this protective action.

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“…Rats were treated intragastrically twice daily with either 50 g/kg misoprostol or its vehicle for 3 or 6 days starting 3 days after ulcer induction. The misoprostol dose used in this study was 20 times lower than that required to significantly inhibit gastric acid output in rats (7). Therefore, any action of misoprostol on esophageal ulcer healing was entirely independent of its inhibitory effect on gastric acid secretion.…”

Section: Methodsmentioning

confidence: 99%