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.

[1]  M. Razandi,et al.  Human cell line for study of damage to gastric epithelial cells in vitro. , 1988, The Journal of laboratory and clinical medicine.

[2]  A. Tarnawski,et al.  Prostaglandin protection of human isolated gastric glands against indomethacin and ethanol injury. Evidence for direct cellular action of prostaglandin. , 1988, The Journal of clinical investigation.

[3]  K. Sewing,et al.  Effect of omeprazole on eicosanoid formation in and release from guinea‐pig gastric mucosal cells , 1987, British journal of pharmacology.

[4]  A. Terano,et al.  Prostaglandin protects against taurocholate-induced damage to rat gastric mucosal cell culture. , 1987, Gastroenterology.

[5]  B. Peskar,et al.  Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa. , 1986, Prostaglandins.

[6]  D. Carter,et al.  Effect of cimetidine and omeprazole on aspirin- and taurocholate-induced gastric mucosal damage in the rat. , 1985, Gut.

[7]  L. Harker,et al.  Glutathione redox cycle protects cultured endothelial cells against lysis by extracellularly generated hydrogen peroxide. , 1984, The Journal of clinical investigation.

[8]  A. Terano,et al.  Effect of 16,16 dimethyl prostaglandin E2 on aspirin induced damage to rat gastric epithelial cells in tissue culture. , 1984, Gut.

[9]  H. Mattsson,et al.  Omeprazole provides protection against experimentally induced gastric mucosal lesions. , 1983, European journal of pharmacology.

[10]  U. Haglund,et al.  Effect of omeprazole--a gastric proton pump inhibitor--on pentagastrin stimulated acid secretion in man. , 1983, Gut.

[11]  S. Ito,et al.  Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin. , 1982, Gastroenterology.

[12]  S. Szabó,et al.  Sulfhydryl compounds may mediate gastric cytoprotection. , 1981, Science.

[13]  G. Sachs,et al.  Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+) ATPase , 1981, Nature.

[14]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[15]  H. Wigzell.  QUANTITATIVE TITRATIONS OF MOUSE H‐2 ANTIBODIES USING Cr51‐LABELLED TARGET CELLS , 1965, Transplantation.

[16]  E. Beutler,et al.  Improved method for the determination of blood glutathione. , 1963, The Journal of laboratory and clinical medicine.

[17]  D. B. Duncan.  MULTIPLE RANGE AND MULTIPLE F TESTS , 1955 .

[18]  K. Takeuchi,et al.  16,16-Dimethyl prostaglandin E2 protects gastric mucosal surface epithelial cells from indomethacin-induced damage in rats. , 1987, Japanese journal of pharmacology.

[19]  H. Mattsson.  Protective Effects of Omeprazole in the Gastric Mucosa , 1986 .

[20]  S. Okabe,et al.  Cytoprotective effects of NC-1300 and omeprazole on Hcl . ethanol-induced gastric lesions in rats. , 1986, Japanese journal of pharmacology.

[21]  J. Stachura,et al.  Prostaglandin protection of the gastric mucosa against alcohol injury--a dynamic time-related process. Role of the mucosal proliferative zone. , 1985, Gastroenterology.

[22]  B. Rush,et al.  Timoprazole is a unique cytoprotective agent in the rat. , 1984, Digestion.

[23]  T. Brzozowski,et al.  Protective action of omeprazole, a benzimidazole derivative, on gastric mucosal damage by aspirin and ethanol in rats. , 1983, Digestion.