Digestive Diseases and Sciences

, Volume 58, Issue 4, pp 950–958 | Cite as

Orally Administered Phosphatidic Acids and Lysophosphatidic Acids Ameliorate Aspirin-Induced Stomach Mucosal Injury in Mice

  • Tamotsu Tanaka
  • Katsuya Morito
  • Masafumi Kinoshita
  • Mayumi Ohmoto
  • Mai Urikura
  • Kiyoshi Satouchi
  • Akira Tokumura
Original Article



Recent investigations revealed that lysophosphatidic acid (LPA), a phospholipid with a growth factor-like activity, plays an important role in the integrity of the gastrointestinal tract epithelium.


This paper attempts to clarify the effect of orally administered phosphatidic acid (PA) and LPA on aspirin-induced gastric lesions in mice.

Materials and Methods

Phospholipids, a free fatty acid, a diacylglycerol and a triglyceride at 1 mM (5.7 μmol/kg body weight) or 0.1 mM were orally administered to mice 0.5 h before oral administration of aspirin (1.7 mmol/kg). The total length of lesions formed on the stomach wall was measured as a lesion index. Formation of LPA from PA in the mouse stomach was examined by in vitro (in stomach lavage fluid), ex vivo (in an isolated stomach) and in vivo (in the stomach of a living mouse) examinations of phospholipase activity.


Palmitic acid, dioleoyl-glycerol, olive oil and lysophosphatidylcholine did not affect the aspirin-induced lesions. In contrast, phosphatidylcholine (1 mM), LPA (1 mM) and PA (0.1, 1 mM) significantly reduced the lesion index. Evidence for formation of LPA from PA in the stomach by gastric phospholipase A2 was obtained by in vitro, ex vivo and in vivo experiments. An LPA-specific receptor, LPA2, was found to be localized on the gastric surface-lining cells of mice.


Pretreatment with PA-rich diets may prevent nonsteroidal anti-inflammatory drug-induced stomach ulcers.


Lysophosphatidic acid Phosphatidic acid Non-steroidal anti-inflammatory drug-induced ulcer Phospholipase A2 Dietary lipids 







Free fatty acid


Hematoxylin and eosin




Lysophosphatidic acid




Mammalian target of rapamycin


Matrix-assisted laser desorption ionization time-of-flight mass spectrometry


Sodium deoxycholate


Nonsteroidal anti-inflammatory drugs


Phosphatidic acid










Tris-buffered saline






Thin-layer chromatography


Phospholipase A2


Phospholipase D



This work was partly supported by grants-in-aid from the Ministry of Education, Science, Sports, and Culture of Japan (21580141) and by a grant from the Kiei-kai Research Foundation in 2011.

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Tamotsu Tanaka
    • 1
  • Katsuya Morito
    • 1
  • Masafumi Kinoshita
    • 1
  • Mayumi Ohmoto
    • 1
  • Mai Urikura
    • 2
  • Kiyoshi Satouchi
    • 2
  • Akira Tokumura
    • 1
  1. 1.Institute of Health BiosciencesUniversity of Tokushima Graduate SchoolTokushimaJapan
  2. 2.Department of Nutrition and Life ScienceFukuyama UniversityFukuyamaJapan

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