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Protection by nitecapone against sodium taurocholate-induced damage to cultured gastric cells

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Abstract

The goal of this study was to observe if nitecapone protected against taurocholate-induced damage in primary cultured rat gastric mucosal cells, as well as in a well-differentiated human gastric epithelial cell line (MKN 28). Prostaglandins were measured to analyze the protection mechanism. In primary rat gastric mucosal cell culture, nitecapone 125–250 μM protected the cells significantly against damage induced by sodidum taurocholate, increasing cell viability by 31–38%. In the human gastric epithelial cell line, in which mitochondrial activity was measured as an indication of cell viability, nitecapone (62.5–250 μM) protected the cells against sodium taurocholate-induced damage by 12–20%. Prostaglandin E2, thromboxane B2, and 6-keto-prostaglandin F1α measurements in the primary cultured rat gastric mucosal cells showed that nitecapone (125 μM and 250 μM) significantly stimulated prostaglandin E2 production (84.7% and 61.0%, respectively), and inhibited thromboxane B2 formation (50% at 250 μM), while the 6-keto-prostaglandin F1α formation was unaffected. Nitecapone had no effect on prostaglandin E2 production in the MKN 28 epithelial cell line. Indomethacin or aspirin, at concentrations that did not affect cell viability, antagonized the stimulative effect of nitecapone on prostaglandin E2 formation in the primary cultured rat gastric mucosal cells. Although the prostaglandin E2 synthesis was blocked, nitecapone still protected against cell damage induced by taurocholate. These results demonstrated the direct and efficacious protection of nitecapone on gastric cell level and suggest that the “cytoprotection” by nitecapone against taurocholate may not be mediated through the mechanism of stimulated synthesis of prostaglandin E2.

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References

  1. Aho P, Lindén I-B: Role of gastric mucosal eicosanoid production in the cytoprotection induced by nitecapone. Scand J Gastroenterol (in press)

  2. Pohto P, Aho P, Lindén I-B: Prevention of gastric and duodenal ulcer in rat models by nitecapone. Eur J Pharmacol 183:314, 1990 (abstract)

    Google Scholar 

  3. Aho P, Savolainen P, Lindén I-B, Pohto P: Duodenal stimulation of bicarbonate by nitecapone. Eur J Pharmacol 183:2190, 1990 (abstract)

    Google Scholar 

  4. Korkolainen T, Nissinen E, Aho P, Lotta T, Lindén I-B: Gastroprotective agent nitecapone reacts with sulfhydryl groups. Eur J Pharmacol 183:315–316, 1990 (abstract)

    Google Scholar 

  5. Nissinen E, Lindén I-B, Schultz E, Kaakkola S, Männistö PT, Pohto P: Inhibition of catechol-O-methyltransferase activity by two novel disubstituted catechols in the rat. Eur J Pharmacol 153:263–269, 1988

    Google Scholar 

  6. Piotrowski J, Slomiany A, Liu J, Fekete Z, Slomiany BL: Effect of nitecapone on the proteolytic and lipolytic activities ofHelicobacter pylori. Life Sci Adv Biochem Pharmacol (in press)

  7. Bennett A, Murray JG, Wyllie JH: Occurrence of prostaglandin E2 in the human stomach, and a study of its effects on human isolated gastric muscle. Br J Pharmacol 32:339–349, 1968

    Google Scholar 

  8. Pace-Asciak C, Wolfe LS: A novel prostaglandin derivative formed from arachidonic acid by rat stomach homogenates. Biochemistry 10:3657–3664, 1971

    Google Scholar 

  9. Pace-Asciak C: Catecholamine induced increase in prostaglandin E biosynthesis in homogenates of the rat stomach fundus.In Advances in the Biosciences. S Bergström, S Bernhard (eds). Oxford, Pergamon-Vieweg, 1973, pp 29–33

    Google Scholar 

  10. Vahi R, Guttman FM, Mitmaker B: Mechanism of cytoprotective effects of PGE2. Surg Forum 30:332–334, 1979

    Google Scholar 

  11. Tarnawski A, Hollander D, Stachura J, Krause WJ, Gergely H: Prostaglandin protection of the gastric mucosa against alcohol injury—a dynamic time-related process; role of the mucosal proliferative zone. Gastroenterology 88:334–352, 1985

    Google Scholar 

  12. Szabo S, Hollander D: Pathways of gastrointestinal protection and repair. Am J Med 86(6A):23–31, 1989

    Google Scholar 

  13. Lacy ER, Ito S: Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin. Gastroenterology 83:619–625, 1982

    Google Scholar 

  14. Guth PH, Paulsen G, Nagata H: Histologic and microciruculatory changes in alcohol-induced gastric lesions in the rat: Effect of prostaglandin cytoprotection. Gastroenterology 87:1083–1090, 1984

    Google Scholar 

  15. Terano A, Ota S, Mach T, Hiraishi H, Stachura J, Tarnawski A, Ivey KJ: Prostaglandin protects against taurocholate-induced damage to rat gastric mucosal cell culture. Gastroenterology 92:669–677, 1987

    Google Scholar 

  16. Konturek SJ, Brzozowski T, Radecki T, Dobrzanska M: Generation of endogenous prostaglandins and thromboxanes in taurocholate-induced gastric mucosal lesions. Scand J Gastroenterol 19:91–96, 1984

    Google Scholar 

  17. Terano A, Ivey KJ, Stachura J, Sekhon S, Hosojima H, McKenzie WN, Krause WJ, Wyche JH: Cell culture of rat gastric fundic mucosa. Gastroenterology 83:1280–1291, 1982

    Google Scholar 

  18. Hojo H: Establishmment of cultured lines of human stomach cancer. Origin and their morphological characteristics. Niigata Igakukai Zassi 91:737–763, 1977

    Google Scholar 

  19. Romano M, Razandi M, Sekhon S, Krause WJ, Ivey KJ: Human cell line for study of damage to gastric epithelial cellsin vitro. J Lab Clin Med 111:430–440, 1988

    Google Scholar 

  20. Nachlas MM, Tsou KC, Souza ED, Cheng CS, Seligman AM: Cytochemical demonstration of succinic dehydrogenase by the use of a newp-nitrophenyl substituted ditetrazolo. J Histochem Cytochem 5:420–436, 1957

    Google Scholar 

  21. Bowie DJ: A method for staining the pepsinogen granules in gastric glands. Anat Rec 64(3):357–367, 1935

    Google Scholar 

  22. Phillips HJ: Dye exclusion tests for cell viability.In Tissue Culture Methods and Applications. PF Krause, MK Patterson (eds). New York, Academic Press, 1973, pp 406–408

    Google Scholar 

  23. Hansen MB, Nielsen SE, Berg K: Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 119:203–210, 1989

    Google Scholar 

  24. Romano M, Razandi M, Ivey KJ: Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture. Dig Dis Sci 35(4):467–476, 1990

    Google Scholar 

  25. Romano M, Razandi M, Ivey KJ: Acetaminophen directly protects human gastric epithelial cell monolayers against damage induced by sodium taurocholate. Digestion 40:181–190, 1988

    Google Scholar 

  26. Ota S, Razandi M, Terano A, Hiraishi H, Ivey KJ: Arachidonic acid does not protect against sodium taurocholate damage to rat gastric epithelial cell cultures. Gastroenterol Jpn 22(3):285–291, 1987

    Google Scholar 

  27. Poon YK, Cho CH, Ogle CW: The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage in rats. J Pharm Pharmacol 41:563–565, 1989

    Google Scholar 

  28. Szabo S, Brown A: Prevention of ethanol-induced vascular injury and gastric mucosal lesions by sucralfate and its components: possible role of endogenous sulfhydryls. Proc Soc Exp Biol Med 185:493–497, 1987

    Google Scholar 

  29. Carlin G, Arfors KE: Peroxidation of liposomes promoted by human polymorphonuclear leukocytes. Free Radic Biol Med 1:437–442, 1985

    Google Scholar 

  30. Gough DB, Boyle B, Joyce WP, Delaney CP, McGeeney KF, Gorey TF, Fitzpatrick JM: Free radical inhibition and serial chemiluminescence in evolving experimental pancreatitis. Br J Surg 77:1256–1259, 1990

    Google Scholar 

  31. Nissinen E, Lindén I-B, Penttila KE, Ranta S, Pohto P: Antioxidant properties of the gastropotective agent nitecapone. Gastroenterology 100:131, 1991 (abstract)

    Google Scholar 

  32. Slomiany BL, Piotrowski J, Ismail A, Rajiyah G, Tamura S, Bielanski W, Slomiany A: Protection against alcohol-induced gastric mucosal injury by nitecapone. Gen Pharmacol 22:1055–1062, 1991

    Google Scholar 

  33. Bighley D, Giesing D: Mechanism of action studies of sucralfate.In Duodenal Ulcer, Gastric Ulcer: Sucralfate. A New Therapeutic Concept. WF Caspary (ed). Baltimore, Urban & Schwarzenberg, 1981, pp 3–12

    Google Scholar 

  34. Kiviluoto T, Voipio J, Kivilaakso E: Subepithelial tissue pH of rat gastric mucosa exposed to luminal acid, barrier breaking agents, and hemorrhagic shock. Gastroenterology 94(3):695–702, 1988

    Google Scholar 

  35. Kiviluoto T, Mustonen H, Kivilaakso E: Effect of barrier-breaking agents on intracellular pH and epithelial membrane resistances: Studies in isolatedNectures antral mucosa exposed to luminal acid. Gastroenterology 96(6):1410–1418, 1989

    Google Scholar 

  36. Postius S, Ruoff H-J, Szelenyi I: Prostaglandin formation by isolated gastric parietal and nonparietal cells of the rat. Br J Pharmacol 84:871–877, 1985

    Google Scholar 

  37. Schepp W, Steffen B, Schusdziarra V, Classen M: Calcium, calmodulin, and cyclic adenosine monophosphate modulate prostaglandin E2 release from isolated human gastric mucosal cells. J Clin Endocrinol Metab 63:886–891, 1986

    Google Scholar 

  38. Mosmann T: Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63, 1983

    Google Scholar 

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Authors and Affiliations

  1. Orion-Farmos Pharmaceuticals, Orion Research Center, P.O. Box 65, SF-02101, Espoo, Finland

    Yahong Tu MD, Sirpa Ranta MSc, Erkki Nissinen PhD &  Inge-Britt Lindén PhD

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  1. Yahong Tu MD
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  2. Sirpa Ranta MSc
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  3. Erkki Nissinen PhD
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  4. Inge-Britt Lindén PhD
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Tu, Y., Ranta, S., Nissinen, E. et al. Protection by nitecapone against sodium taurocholate-induced damage to cultured gastric cells. Digest Dis Sci 38, 701–707 (1993). https://doi.org/10.1007/BF01316803

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  • DOI: https://doi.org/10.1007/BF01316803

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