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Intragastrically Administered Lysophosphatidic Acids Protect Against Gastric Ulcer in Rats Under Water-Immersion Restraint Stress

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Abstract

Background and Aim

Lysophosphatidic acid exerts important physiological effects on many types of animal cells through its specific binding to several G protein-coupled receptors. In particular, its potent wound-healing effect has attracted much attention. To determine whether lysophosphatidic acids in a foodstuff and Chinese medicine are effective in protecting against gastric ulcer, we subjected rats to water-immersion restraint stress.

Methods and Results

Three direct administrations of a solution of lysophosphatidic acid with a C18 fatty acyl group to the rat stomach in a concentration range of 0.001–0.1 mM resulted in a significant reduction in the number of gastric ulcers induced during water-immersion restraint stress, and the potencies were as follows: linoleoyl species = α-linolenoyl species > oleoyl species. Intragastric administrations of a solution of highly purified lysophosphatidic acid from soybean lecithin significantly protected against the stress-induced gastric ulcers at lower concentrations than partially purified lysophosphatidic acid from soybean lecithin did. In addition, administration of a decocted solution of antyu-san, and lysophosphatidic acid-rich Chinese medicine, to the stomach was more effective in protecting against stress-induced ulcer than decoctations of antyu-san lacking the corydalis tuber component that is rich in lysophosphatidic acid.

Conclusions

These results clearly show that lysophosphatidic acid is the effective component of soybean lecithin and antyu-san in protection against stress-induced gastric ulcer in the rat model, and suggest that daily intake of lysophosphatidic acid-rich foods or Chinese medicines may be beneficial for prevention of stress-induced gastric ulcer in human subjects.

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Notes

  1. The fatty acyl moieties of phospholipids are designated in terms of the number of carbon atoms and double bonds: 16:0, palmitoyl group; 16:1, palmitoleoyl group; 18:0, stearoyl group; 18:1, oleoyl group; 18:2, linoleoyl group; and 18:3, α-linolenoyl group.

References

  1. Tokumura A, Fukuzawa K, Akamatsu Y, Yamada S, Suzuki T, Tsukatani H. Identification of vasopressor phospholipid in crude soybean lecithin. Lipids. 1978;13:468–472.

    Article  PubMed  CAS  Google Scholar 

  2. Funk-Archelta MA, Foeh MW, Tomei LD, Hennebold KL, Bathurst IC. Soy-derived antiapoptotic fraction decreases methotrexate toxicity in the gastrointestinal tract of the rat. Nutr Cancer. 1997;29:217–221.

    Article  Google Scholar 

  3. Logvinova AV, Foeh MW, Pemberton PA, et al. Soy-derived antiapoptotic fractions protect gastrointestinal epithelium from damage caused by methotrexate treatment in the rats. Nutr Cancer. 1999;33:33–39.

    Article  PubMed  CAS  Google Scholar 

  4. Sturm A, Sudermann T, Schulte K-M, Goebell H, Dignass AU. Modulation of intestinal epithelial wound healing in vitro and in vivo by lysophosphatidic acid. Gastroenterology. 1999;117:368–377.

    Article  PubMed  CAS  Google Scholar 

  5. Sturm A, Zeeh J, Sudermann T, Rath H, Gerken G, Dignass AU. Lisofylline and lysophospholipids ameliorate experimental colitis in rats. Digestion. 2002;66:23–29.

    Article  PubMed  CAS  Google Scholar 

  6. Deng W, Balazs L, Wang D, Van Middlesworth L, Tigyi G, Johnson LR. Lysophosphatidic acid protects and rescues intestinal epithelial cells from radiation- and chemotherapy-induced apoptosis. Gastroenterology. 2002;123:206–216.

    Article  PubMed  CAS  Google Scholar 

  7. Deng W, Shuyu E, Tsukahara R, et al. The lysophosphatidic acid type 2 receptor is required for protection against radiation-induced intestinal injury. Gastroenterology. 2007;132:1834–1851.

    Article  PubMed  CAS  Google Scholar 

  8. Sturm A, Dignass AU. Modulation of gastrointestinal wound repair and inflammation by phospholipids. Biochim Biophys Acta. 2002;1582:282–288.

    PubMed  CAS  Google Scholar 

  9. Minami T, Tojo H, Zushi S, Shinomura Y, Matsuzawa Y. Phospholipase A2 stimulates rat gastric epithelial cell line (RGM-1) migration. Inflamm Res. 1997;46:103–107.

    Article  PubMed  CAS  Google Scholar 

  10. Bhowmik A, Paimela H, Mustonen H, Kivilaakso E. Roles of cytoskeleton and tyrosine receptor mediated signal transduction in the restitution of isolated guinea pig gastric mucosa. Scan J Gastroenterol. 2002;37:759–764.

    Article  CAS  Google Scholar 

  11. Tanaka T, Horiuchi G, Matsuoka M, et al. Formation of lysophosphatidic acid, a wound-healing lipid, during digestion of cabbage leaves. Biosci Biotechnol Biochem. 2009;73:1293–1300.

    Article  PubMed  CAS  Google Scholar 

  12. Moody FG, Cheung LY, Simons MA, Zalewsky C. Stress and the acute gastric mucosal lesion. Am J Dig Dis. 1976;21:148–154.

    Article  PubMed  CAS  Google Scholar 

  13. Brodie DA, Hanson HM. A study of the factors involved in the production of gastric ulcers by the restraint technique. Gastroenterology. 1960;38:353–360.

    PubMed  CAS  Google Scholar 

  14. Takagi K, Okabe S. The effects of drugs on the production and recovery processes of the stress ulcer. Jpn J Pharmacol. 1968;18:9–18.

    Article  PubMed  CAS  Google Scholar 

  15. Shimbo K. High performance liquid chromatography of phospholipids on aminopropyl silica column. Agric Biol Chem. 1986;50:2643–2645.

    Article  CAS  Google Scholar 

  16. Tokumura A, Iimori M, Nishioka Y, Kitahara M, Sakashita M, Tanaka S. Lysophosphatidic acids induce proliferation of cultured vascular smooth muscle cells from rat aorta. Am J Physiol Cell Physiol. 1994;267:C204–C210.

    CAS  Google Scholar 

  17. Tanaka T, Tsutsui H, Hirano K, Koike T, Tokumura A, Satouchi K. Quantitative analysis of lysophosphatidic acid by time-of-flight mass spectrometry using a phosphate-capture molecule. J Lipid Res. 2004;45:2145–2150.

    Article  PubMed  CAS  Google Scholar 

  18. Tokumura A, Carbone LD, Yoshioka Y, et al. Elevated serum levels of arachidonoyl-lysophosphatidic acid and sphingosine 1-phosphate in systemic sclerosis. Int J Med Sci. 2009;6:168–176.

    PubMed  CAS  Google Scholar 

  19. Morishige J, Urikura M, Takagi H, et al. A clean-up technology for the simultaneous determination of lysophosphatidic acid and sphingosine-1-phosphate by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using a phosphate-capture molecule, Phos-tag. Rapid Commun Mass Spectrom. 2010;24:1075–1084.

    Article  PubMed  CAS  Google Scholar 

  20. Oblozinsky M, Schoeps R, Ulbrich-Hofmann R, Bezakova L. Two uncommon phospholipase D isoenzymes from poppy seedlings (Papaver somniferum L.). Biochim Biophys Acta. 2003;1631:153–159.

    PubMed  CAS  Google Scholar 

  21. Marrone GC, Silen W. Pathogenesis, diagnosis and treatment of acute gastric mucosal lesions. Clin Gastroenterol. 1984;13:635–650.

    PubMed  CAS  Google Scholar 

  22. Kitagawa H, Fujiwara M, Osumi Y. Effects of water-immersion stress on gastric secretion and mucosal blood flow in rats. Gastroenterology. 1979;77:298–302.

    PubMed  CAS  Google Scholar 

  23. Harada N, Okajima K, Liu W. Rebamipide decreases the susceptibility of gastric mucosa to acid-induced injury in rats by inhibiting neutrophil activation. Dig Dis Sci. 2005;50:S56–S62.

    Article  PubMed  CAS  Google Scholar 

  24. Hamajima E, Sugiyama S, Hoshino H, Goto H, Tsukamoto Y, Ozawa T. Effect of FK506, an immunosuppressive agent, on genesis of water-immersion stress-induced gastric lesions in rats. Dig Dis Sci. 1994;39:713–720.

    Article  PubMed  CAS  Google Scholar 

  25. Kitagawa H, Takeda F, Kohei H. A simple method for estimation of gastric mucus and effects of antiulcerogenic agents on the decrease in mucus during water-immersion stress in rats. Arzneimittelforschung. 1986;36:1240–1244.

    PubMed  CAS  Google Scholar 

  26. Li J, Takeda H, Inazu M, et al. Protective effects of Hange-shashin-to on water-immersion restraint stress induced gastric ulcer. Methods Find Exp Clin Pharmacol. 1998;20:31–37.

    Article  PubMed  CAS  Google Scholar 

  27. Yoshikawa T, Naito Y, Ueda S, et al. Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats. J Clin Gastroenterol. 1990;12(Suppl 1):S65–S71.

    Article  PubMed  Google Scholar 

  28. Liu W, Okajima K, Murakami K, Harada N, Isobe H, Irie T. Role of neutrophil elastase in stress-induced gastric mucosal injury in rats. J Lab Clin Med. 1998;132:432–439.

    Article  PubMed  CAS  Google Scholar 

  29. Harada N, Okajima K, Murakami K, Isobe H, Liu W. Gastric prostacyclin (PGI2) prevents stress-induced gastric mucosal injury in rats primarily by inhibiting leukocyte activation. Prostaglandins Other Lipid Mediat. 1999;57:291–303.

    Article  PubMed  CAS  Google Scholar 

  30. Domirbilek S, Gürses I, Sezgin N, Karaman A, Gürbüz N. Protective effect of polyunsaturated phosphatidylcholine pretreatment on stress ulcer formation in rats. J Pediatr Surg. 2004;39:57–62.

    Article  Google Scholar 

  31. Dunjic BS, Axelson J, Ar’Rajab A, Larsson K, Bengmark S. Gastroprotective capability of exogenous phosphatidylcholine in experimentally induced chronic gastric ulcers in rats. Scan J Gastroenterol. 1993;28:89–94.

    Article  CAS  Google Scholar 

  32. Goggin PM, Northfield TC, Spychal RT. Factors affecting gastric mucosal hydrophobicity in man. Scan J Gastroenterol Suppl. 1991;181:65–73.

    Article  CAS  Google Scholar 

  33. Watanabe T, Ohara S, Ichikawa T, Saigenji K, Hotta K. Mechanisms for cytoprotection by vitamin U from ethanol-induced gastric mucosal damage in rats. Dig Dis Sci. 1996;41:49–54.

    Article  PubMed  CAS  Google Scholar 

  34. Ichikawa T, Ito Y, Saegusa Y, et al. Effects of combination treatment with famotidine and methylmethionine sulfonium chloride on the mucus barrier of rat gastric mucus. J Gastroenterol Hepatol. 2009;24:488–492.

    Article  PubMed  CAS  Google Scholar 

  35. Akhatar MS, Munir M. Evaluation of the gastric antiulcerogenic effects of Solanum nigrum, Brassica oleracea and Ocimum basilicum in rats. J Ethnophramacol. 1989;27:163–176.

    Article  Google Scholar 

  36. Shida D, Kitayama J, Yamaguchi H, et al. Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells. Exp Cell Res. 2004;301:168–178.

    Article  PubMed  CAS  Google Scholar 

  37. Kim MH, Park JS, Chang HJ, et al. Lysophosphatidic acid promotes cell invasion by up-regulating the urokinase-type plasminogen activator receptor in human gastric cancer cells. J Cell Biochem. 2008;104:1102–1112.

    Article  PubMed  CAS  Google Scholar 

  38. Mori K, Kitayama J, Aoki J, et al. Submucosal connective tissue-type mast cells contribute to the production of lysophosphatidic acid (LPA) in the gastrointestinal tract through the secretion of autotaxin (ATX)/lysophospholipase D (lysoPLD). Virchows Arch. 2007;451:47–56.

    Article  PubMed  CAS  Google Scholar 

  39. Rosam AC, Wallace JL, Whittle BJ. Potent ulcerogenic actions of platelet-activating factor on the stomach. Nature. 1986;319:54–56.

    Article  PubMed  CAS  Google Scholar 

  40. Sugatani J, Miwa K, Fujimura K, Suzuki Y, Saito K. The role of endogenous platelet-activating factor in the stomach. Jpn J Inflammation. 1992;12:447–452.

    Google Scholar 

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Acknowledgments

We thank Drs. T. Yamaguchi. K. Fujimura, and H. Sakakibara, for their kind advice on evaluation of gastric ulcer in water-immersion stress loaded rat, and Y. Adachi for providing dried components of AS for preparation of hot water decoctions of AS with and without corydalis tuber. This study was supported in part by a research for Promotion Technological Seeds 13-042 from JST (AT).

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Authors and Affiliations

  1. Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, 1-78-1 Shomachi, Tokushima, 770-8505, Japan

    Mika Adachi, Tamotsu Tanaka & Akira Tokumura

  2. Faculty of Life Science and Biotechnology, Fukuyama University, 1 Gakuencho, Fukuyama, 729-0292, Japan

    Gou Horiuchi, Natsuki Ikematsu & Kiyoshi Satouchi

  3. Department of Food Chemistry, Graduate School of Nutrition and Bioscience, Institute of Health Biosciences, University of Tokushima, 3-18 Kuramot-ocho, Tokushima, 770-8503, Japan

    Junji Terao

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  1. Mika Adachi
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Correspondence to Akira Tokumura.

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Adachi, M., Horiuchi, G., Ikematsu, N. et al. Intragastrically Administered Lysophosphatidic Acids Protect Against Gastric Ulcer in Rats Under Water-Immersion Restraint Stress. Dig Dis Sci 56, 2252–2261 (2011). https://doi.org/10.1007/s10620-011-1595-0

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  • DOI: https://doi.org/10.1007/s10620-011-1595-0

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