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

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Abstract

Background

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.

Aim

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.

Results

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.

Conclusion

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

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Abbreviations

COX:

Cyclooxygenase

CMC:

Carboxymethylcellulose

FFA:

Free fatty acid

HE:

Hematoxylin and eosin

GI:

Gastrointestinal

LPA:

Lysophosphatidic acid

LPC:

Lysophosphatidylcholine

mTOR:

Mammalian target of rapamycin

MALDI-TOF MS:

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

NaDOC:

Sodium deoxycholate

NSAIDs:

Nonsteroidal anti-inflammatory drugs

PA:

Phosphatidic acid

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PG:

Prostaglandin

PI:

Phosphatidylinositol

TBS:

Tris-buffered saline

TG:

Triglyceride

THAP:

2,4,6-Trihydroxyacetophenone

TLC:

Thin-layer chromatography

PLA2 :

Phospholipase A2

PLD:

Phospholipase D

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Acknowledgments

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

None.

Author information

Authors and Affiliations

  1. Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, 770-8505, Japan

    Tamotsu Tanaka, Katsuya Morito, Masafumi Kinoshita, Mayumi Ohmoto & Akira Tokumura

  2. Department of Nutrition and Life Science, Fukuyama University, Fukuyama, 729-0292, Japan

    Mai Urikura & Kiyoshi Satouchi

Authors
  1. Tamotsu Tanaka
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  2. Katsuya Morito
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  3. Masafumi Kinoshita
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  4. Mayumi Ohmoto
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  5. Mai Urikura
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  6. Kiyoshi Satouchi
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  7. Akira Tokumura
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Corresponding author

Correspondence to Tamotsu Tanaka.

Additional information

The fatty acyl moieties of lipids are designated in terms of the number of carbon atoms and double bonds: 16:0, palmitoyl group; 18:1, oleoyl group; 18:2, linoleoyl group.

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Tanaka, T., Morito, K., Kinoshita, M. et al. Orally Administered Phosphatidic Acids and Lysophosphatidic Acids Ameliorate Aspirin-Induced Stomach Mucosal Injury in Mice. Dig Dis Sci 58, 950–958 (2013). https://doi.org/10.1007/s10620-012-2475-y

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  • DOI: https://doi.org/10.1007/s10620-012-2475-y

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