Skip to main content
Log in

Effects of Omeprazole and Ascorbate on Gastric Emptying and Antioxidant Levels in a Mouse Model of Glutathione Depletion

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Increased free radical production with depletion of the antioxidant, glutathione, is a suggested mechanism for the development of ulcer disease in patients with Helicobacter pylori. The effects of ascorbate and omeprazole as potential gut antioxidants are incompletely understood. We hypothesized that as antioxidants, ascorbate and omeprazole protect against glutathione depletion. This study was designed to determine the effects of ascorbate and omeprazole on gastric emptying and gastric antioxidant levels in a mouse model of glutathione depletion. In an acute (10-day) mouse model, glutathione depletion was induced by inhibiting the rate limiting enzyme, γ-glutamylcysteine synthetase. Enzymatic blockade produced depletion of gastric glutathione (P < 0.05) without increasing gastric lipid hydroperoxides. Glutathione depletion was associated with accelerated liquid gastric emptying. These effects were not prevented by supplementation with ascorbate or omeprazole. Omeprazole induced increased (P < 0.05) gastric and colonic total antioxidant capacity. One of the beneficial effects of omeprazole in patients may involve increased total antioxidant capacity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Khaleld MA, Sarker SA: Changes of oxidant and antioxidant status in humans due to H. pylori infection. Nutr Res 18(9):1463–1468, 1998

    Google Scholar 

  2. Drake IM, Mapstone NP, Schorah CJ, White KLM, Chalmers DM, Dixon MF, Axon ATR: Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication. Gut 42:768–771, 1998

    Google Scholar 

  3. Farinati F, Libera GD, Cardin R, Molari A, Plebani M, Rugge M, Di Mario F, Naccaroto R: Gastric antioxidant, nitrites, and mucosal lipoperoxidation in chronic gastritis and Helicobacter pylori infection. J Clin Gastroenterol 22(4):275–281, 1996

    Google Scholar 

  4. Verhulst M-L, Van Oijen AHAM, Roelofs HMJ, Peters WHM, Jansen JBMJ: Antral glutathione concentration and glutathione S-transferase activity in patients with and without Helicobacter pylori. Dig Dis Sci 45:629–632, 2000

    Google Scholar 

  5. Beil W, Obst B, Sewing K-F, Wagner S: Helicobacter pylori reduces intracellular glutathione in gastric epithelial cells. Dig Dis Sci 45:1769–1773, 2000

    Google Scholar 

  6. Martensson J, Jain A, Meister A: Glutathione is required for intestinal function. Proc Natl Acad Sci USA 87:1715–1719, 1990

    Google Scholar 

  7. White AC, Thannickal VJ, Fanburg BL: Glutathione deficiency in human disease. J Nutr Biochem 5:218–226, 1994

    Google Scholar 

  8. Shibata A, Paganini-Hill A, Ross RK, Henderson BE: Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer 66:673–679, 1992

    Google Scholar 

  9. Mowat C, Carswell A, Wirz A, McColl KEL: Omeprazole and dietary nitrate independently affect levels of vitamin C and nitrite in gastric juice. Gastroenterology 116:813–822, 1999

    Google Scholar 

  10. Lapenna D, de Gioia S, Ciofani G, Festi D, Cuccurullo F: Antioxidant properties of omeprazole. FEBS Lett 382:189–192, 1996

    Google Scholar 

  11. Kawamura T, Miyaji C, Toyabe S, Fukuda M, Watanabe H, Abo T: Suppressive effect of antiulcer agents on granulocytes-a role for granulocytes in gastric ulcer formation. Dig Dis Sci 45:1786–1791, 2000

    Google Scholar 

  12. Wandall JH. Effects of omeprazole on neutrophil chemotaxis, super oxide production, degranulation, and translocation of cytochrome b 245: Gut 33:617–621, 1992

    Google Scholar 

  13. Suzuki M, Mori M, Miura S, Suematsu M, Fukumura D, Kimura H, Ishii H: Omeprazole attenuates oxygen-derived free radical production from human neutrophils. Free Radic Biol & Med 21:727–731, 1996

    Google Scholar 

  14. Martensson J, Jain A, Stole E, Frayer W, Auld PAM, Meister A: Inhibition of glutathione synthesis in the newborn rat: A model for endogenously produced oxidative stress. Proc Natl Acad Sci USA 88:9360–9364, 1991

    Google Scholar 

  15. Carlsson E, Larsson H, Mattsson H, Ryberg B, Sundell G: Pharmacology and toxicology of omeprazole-with special reference to the effects on the gastric mucosa. Scand J Gastroenterol 21(suppl 118):31–38, 1986

    Google Scholar 

  16. Koch TR, Yuan L-X, Fink JG, Petro A, Opara EC: Induction of enlarged intestinal lymphoid aggregates during acute glutathione depletion in a murine model. Dig Dis Sci 45:2115–2121, 2000

    Google Scholar 

  17. Ballard TC, Farag A, Branum GD, Akwari OE, Opara EC: Effect of L-glutamine supplementation on impaired glucose regulation during intravenous lipid administration. Nutrition 12:349–354, 1996

    Google Scholar 

  18. Abdella N, Al Awadi F, Salman A, Armstrong D: Thiobarbituric acid test as a measure of lipid peroxidation in Arab patients with NIDDM. Diabetes Res 15:173–177, 1990

    Google Scholar 

  19. Bicheler V, Cherbut C, Ropert A, Roze C, Galmiche JP: Peptide YY increases gastric emptying in rats. Gastroenterology 114(4):A721, 1998

    Google Scholar 

  20. Matsuda M, Aono M, Moriga M, Okuma M: Centrally administered neuropeptide Y (NPY) inhibits gastric emptying and intestinal transit in the rat. Dig Dis Sci 38:845–850, 1993

    Google Scholar 

  21. Pellegrini N, Re R, Yang M, Rice-Evans C: Screening of dietary carotenoids and carotenoids-rich fruit extracts for antioxidant activities applying 2,2'-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid radical cation decolorization assay. Methods Enzymol 299:379–389, 1998

    Google Scholar 

  22. Koch TR, Yuan L-X, Stryker SJ, Ratliff P, Telford GL, Opara EC: Total antioxidant capacity of colon in patients with chronic ulcerative colitis. Dig Dis Sci 45:1814–1819, 2000

    Google Scholar 

  23. Zar JH. Biostatistical Analysis, 2nd ed. Englewood Cliffs, New Jersey, Prentice-Hall, 1984, pp 171–176

    Google Scholar 

  24. Fordtran JS, Walsh JH: Gastric acid secretion rate and buffer content of the stomach after eating. J Clin Invest 52:645–657, 1973

    Google Scholar 

  25. Howlett PJ, Sheiner HJ, Barber DC, Ward AS, Perez-Avila CA, Duthie HL: Gastric emptying in control subjects and patients with duodenal ulcer before and after vagotomy. Gut 17:542–550, 1976

    Google Scholar 

  26. Cucchiara S, Minella R, Campanozzi A, Salvia G, Borrelli O, Ciccimarra E, Emiliano M: Effects of omeprazole on mechanisms of gastroesophageal reflux in childhood. Dig Dis Sci 42:293–299, 1997

    Google Scholar 

  27. Koskenpato J, Korppi-Tommola T, Kairemo K, Farkkila M: Long-term follow up study of gastric emptying and Helicobacter pylori eradication among patients with functional dyspepsia. Dig Dis Sci 45:1763–1768, 2000

    Google Scholar 

  28. Parkman HP, Urbain J-LC, Knight LC, Brown KL, Trate DM, Miller MA, Maurer AH, Fisher RS: Effect of gastric acid suppressants on human gastric motility. Gut 42:243–250, 1998

    Google Scholar 

  29. Rasmussen L, Oster-Jorgensen E, Qvist N, Pedersen SA: The effects of omeprazole on intragastric pH, intestinal motility, and gastric emptying rate. Scand J Gastroenterol 34:671–675, 1999

    Google Scholar 

  30. Suzuki M, Nakamura M, Mori M, Miura S, Tsuchiya M, Ishii H: Lansoprazole inhibits oxygen-derived free radical production from neutrophils activated by Helicobacter pylori. J Clin Gastroenterol 20(suppl. 2):S93–S96, 1995

    Google Scholar 

  31. Yu BP: Cellular defenses against damage from reactive oxygen species. Physiol Rev 74:139–162, 1994

    Google Scholar 

  32. Van den Berg R, Haenen GRMM, Van den Berg H, Bast A: Applicability of an improved Trolox equivalent antioxidant capacity measurements of mixtures. Food Chem 66:511–517, 1999

    Google Scholar 

  33. Wetscher GJ, Hinder RA, Bagchi D, Hinder PR, Bagchi M, Perdikis G, McGinn T: Reflux esophagitis in humans is mediated by oxygen-derived free radicals. Am J Surg 170:552–557, 1995

    Google Scholar 

  34. Ovrebo KK, Sorbye H, Svardal A, Grong K, Svanes K: Glutathione and N-acetylcysteine reduce gastric mucosal blood flow in rats. Dig Dis Sci 42:1765–1774, 1997

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koch, T.R., Yuan, LX., Petro, A. et al. Effects of Omeprazole and Ascorbate on Gastric Emptying and Antioxidant Levels in a Mouse Model of Glutathione Depletion. Dig Dis Sci 47, 2486–2492 (2002). https://doi.org/10.1023/A:1020555925142

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020555925142

Navigation