Orally Administered Phosphatidic Acids and Lysophosphatidic Acids Ameliorate Aspirin-Induced Stomach Mucosal Injury in Mice
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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.
KeywordsLysophosphatidic acid Phosphatidic acid Non-steroidal anti-inflammatory drug-induced ulcer Phospholipase A2 Dietary lipids
Free fatty acid
Hematoxylin and eosin
Mammalian target of rapamycin
- MALDI-TOF MS
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
Nonsteroidal anti-inflammatory drugs
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
- 26.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.PubMedCrossRefGoogle Scholar