Gastric mucosal protection by spizofurone.
The protective effect of spizofurone (AG-629) on the rat gastric mucosa was studied in the presence of various stimuli. Spizofurone given orally markedly inhibited gastric lesions induced by ethanol (ED50 = 6.5 mg/kg). Spizofurone inhibited ethanol-induced gastric lesions even when administered intraperitoneally (i.p.), but the onset of action after oral administration was shorter. Spizofurone given orally or i.p. in a dose range of 25-200 mg/kg inhibited indomethacin-induced gastric antral ulcers in re-fed rats. Furthermore, spizofurone potentiated the inhibitory effect of prostaglandin E2 on indomethacin-induced gastric antral ulcers. Spizofurone given i.p. prevented a decrease in potential difference and the formation of gastric lesions induced by intragastric instillation of 30 mM aspirin in 0.1 N HCl. Spizofurone given i.p. inhibited the increase in net fluxes of H+ and Na+ caused by intragastric instillation of 15% ethanol in 0.1 N HCl. These findings indicate that spizofurone, like prostaglandin E2, exerts gastric mucosal protection and even potentiates the anti-ulcer effect of prostaglandin E2. The gastric mucosal protection by spizofurone is ascribed in part to preservation of the mucosal barrier.
D000818:Animals; D000897:Anti-Ulcer Agents; D001241:Aspirin; D001572:Benzofurans / Q000494:pharmacology*; D015232:Dinoprostone; D004573:Electrolytes / Q000378:metabolism; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects*; D007213:Indomethacin; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced
D000897:Anti-Ulcer Agents; D001572:Benzofurans; D004573:Electrolytes; D011458:Prostaglandins E; D000431:Ethanol; C045902:spizofurone; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin