No abstract

This study describes the model of chronic gastric and duodenal ulcerations induced by the application of acetic acid on a strictly defined area of the serosal surface of the stomach and duodenum for 10 and 20 s, respectively. Acetic acid applied for longer (20–60 s) or on a larger area (28–64 mm²) resulted in the formation of severe ulcerations which penetrated into the surrounding organs and had very prolonged healing time. Ulcers induced by the application of acetic acid for 10–20 s on a smaller area (7–13.8 mm²) healed spontaneously within 2–3 weeks, thus constituting a model suitable for evaluation of drugs affecting the process of ulcer healing. Our preliminary results of 7- to 14-day treatment with certain drugs indicate that sucralfate and De-Nol, at the dose which does not affect gastric acid secretion, accelerated the healing rate of both gastric and duodenal ulcers so that the observed ulcer healing effect could be attributed to their ulcer healing property. In contrast, 16, 16-dimethyl PGE₂ (dmPGE₂) in cytoprotective dose was completely ineffective in enhancing ulcer healing. Higher, gastric inhibitory dose of dmPGE₂ accelerated the healing of duodenal but not gastric ulcerations, indicating that the inhibition of gastric secretion rather that cytoprotective activity is responsible for ulcer healing effect of this prostaglandin.

This study was designed to determine the role of mucosal generation of prostaglandins (PGs) in the ability of mild irritants (20% ethanol or 5% NaCl) to protect against the formation of mucosal lesions caused by necrotizing agents (100% ethanol or 25% NaCl) or acidified aspirin (ASA). Mild irritants protected damage from necrotizing agents but not from ASA. This protection was accompanied by increased mucosal generation of PGE2 and PGI2-like substances. Exogenous PGE2 and PGI2 applied topically to the gastric mucosa in a nonantisecretory dose greatly inhibited the formation of lesions induced by either necrotizing agents or ASA. Pretreatment with indomethacin, which suppressed the generation of mucosal PGs augmented formation of lesions by necrotizing agents and partly counteracted the protective effect of mild irritants. We conclude that mild irritants, and exogenous PGs inhibit the formation of gastric lesions by necrotizing agents, at least in part, by mucosal generation of PGs.

No abstract

This study was designed to compare the influence of omeprazole, a potent inhibitor of H⁺/K⁺-ATP-ase involved in the final step of H⁺ secretion and prostaglandin (PG) I₂ on the formation of gastric mucosal lesions induced by absolute ethanol or acidified aspirin (ASA). Omeprazole given intragastrically in both inhibitory (20 or 200 μmol/kg) and nonin-hibitory doses (2 μmol/kg) prevented dose dependently ASA- and ethanol-induced gastric lesions. The protective effect of omeprazole against ASA-induced lesions occurred when mucosal generation of PGs was completely suppressed and that against ethanol lesions when PG generation was increased above normal values. Pretreatment with PGI₂ given intragastrically or subcutaneously both in inhibitory and noninhibitory doses prevented almost completely the formation of gastric mucosal lesions caused by both absolute ethanol and acidified ASA. This study indicates that omeprazole is capable of protecting gastric mucosa against ASA- and ethanol-induced injury and that this protection is unrelated to gastric inhibition or the biosynthesis of mucosal PGs.