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Open Access Role of Cytoprotectants and Nitric Oxide Inhibition in Nonsteroidal Anti-inflammatory Drug-Induced Gastroduodenal Injury in the Rat

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Background and Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastroduodenal injury and ulceration. The pathogenesis is uncertain, although reductions in cytoprotective prostaglandins and nitric oxide (NO) have been proposed. The effects of several cytoprotective agents on inhibition of gastroduodenal ulcerogenesis induced by CI-987, a novel NSAID, were evaluated in Wistar rats.

Methods: Male Wistar rats were given CI-987 orally (PO) at a dosage of 300 or 450 mg/kg of body weight or subcutaneously (SC) (3 x 50 mg/kg), alone or with misoprostol pretreatment (2 x 1 mg/kg, PO). In a second experiment, rats were pre-treated with 2 ml of gelusil PO, 500 mg of sucralfate/kg, PO, 100 mg of ranitidine/kg SC, or 200 mg of N -nitro-L-arginine methyl ester (L-NAME)/kg, SC. Duodenal injury was induced by administration of 450 mg of CI-987/kg, PO, 3 x 50 mg of CI-987/kg, SC, or 300 mg of cysteamine/kg, SC. Animals were euthanized within 24 to 48 hours, and the gastrointestinal tract was examined for evidence of gross or microscopic change. Results: The L-NAME significantly reduced the incidence and severity of gastroduodenal injury induced by CI987 and cysteamine. Prostaglandin ameliorated duodenal lesions induced by CI-987 given SC, and Gelusil, ranitidine, and sucralfate were without effect on duodenal lesions induced by NSAID. Conclusions: Preemptive blockade of NO synthase is important in preventing NSAID-induced duodenal injury in rats. Inhibition of cytoprotective prostaglandins and enhanced acid-induced damage are unlikely to be primary mechanisms underlying NSAID-induced duodenal injury in rats.

Document Type: Research Article

Publication date: April 1, 2000

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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