Effects of absolute ethanol, misoprostol, cimetidine, and phosphate buffer on the morphology of rat gastric mucosae

Fasted rats were given a single oral dose of one of the following: a synthetic prostaglandin E1 analog, misoprostol (low dose = 100 micrograms/kg, or high dose = 1 mg/kg), cimetidine (low dose = 100 micrograms/kg, or high dose = 50 mg/kg), phosphate buffer, or absolute ethanol. A second group of rats received a single oral dose of misoprostol, cimetidine, or phosphate buffer intragastrically, followed 30 min later by a second oral dose of absolute ethanol. Stomachs were either surgically removed and examined grossly or were fixed in situ and prepared for histological observation 15 or 30 min after the initial dose, or 15 or 30 min after the second dose. Absolute ethanol alone produced grossly visible hemorrhagic lesions and extensive hyperemia and microscopic damage to the glands, which was largely confined to the crests of the rugae. Microscopic examination of nonhemorrhagic areas showed extensive damage of the superficial and gastric pit epithelial cells as well as some endothelial cells and adjacent structures in the lamina propria. Pretreatment with phosphate buffer, or either dose of cimetidine, did not obviate the gross hemorrhagic lesions or the histologic damage produced by absolute ethanol. Both the low and high doses of misoprostol protected the stomach against ethanol-induced gross hemorrhagic lesions but did not completely protect against microscopic damage to the superficial mucosa.

the protective action of misoprostol involves mechanisms that prevent hemorrhagic lesions but do not completely shield the superficial mucosa from damage. These mechanisms appear to be independent of misoprostol's antisecretory effects.