Protection of gastric epithelial cell monolayers from a human cell line by omeprazole in vitro.
Omeprazole has an anti-ulcerogenic effect and protects rat gastric mucosa against drug-induced damage in vivo. We have evaluated omeprazole protection against damage induced by sodium taurocholate to gastric epithelial cell monolayers, an experimental model that completely excludes the influence of systemic factors. Furthermore, since our model consists of mucus-producing cells, the acid inhibitory effect of the drug in any protection is negligible. The role of prostaglandin and sulfhydryls in any such protection has also been evaluated. Monolayers of gastric cells from a well-differentiated human cell line were studied. A chromium-51 release assay was used to assess cell damage. Sodium taurocholate damaged cells dose-dependently (r = 0.97, p less than 0.01). Pretreatment with omeprazole significantly reduced the amount of cell damage brought about by sodium taurocholate (p less than 0.001). Indomethacin did not prevent the protection afforded by omeprazole, nor did incubation with omeprazole increase the amount of prostaglandin E2 produced by cultured cells. Omeprazole did not increase the amount of sulfhydryl compounds in cultured cells. These results indicate that omeprazole protects gastric cells independently of systemic factors and of inhibition of gastric acid secretion. This protection is not related to stimulation of prostaglandin synthesis nor is it associated with an increase of endogenous sulfhydryl compounds.
Dept. of Medicine, Veterans Administration Medical Center, Long Beach, California 90822.
M
M
Romano
M
M
Razandi
K J
KJ
Ivey
D002460:Cell Line; D002860:Chromium Radioisotopes; D015232:Dinoprostone / Q000096:biosynthesis; D004341:Drug Evaluation; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013656:Taurocholic Acid / Q000494:pharmacology
D002860:Chromium Radioisotopes; D013438:Sulfhydryl Compounds; D013656:Taurocholic Acid; D015232:Dinoprostone; D009853:Omeprazole; D007213:Indomethacin