title: Orally administered phosphatidic acids and lysophosphatidic acids ameliorate aspirin-induced stomach mucosal injury in mice.
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.
  
  
  OBJECTIVE
  This paper attempts to clarify the effect of orally administered phosphatidic acid (PA) and LPA on aspirin-induced gastric lesions in mice.
  
  
  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.
  
  
  CONCLUSIONS
  Pretreatment with PA-rich diets may prevent nonsteroidal anti-inflammatory drug-induced stomach ulcers.
authors.affiliation: Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8505, Japan. tanaka.tamotsu@tokushima-u.ac.jp
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Tanaka
authors.forename: Katsuya
authors.initials: K
authors.lastname: Morito
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ohmoto
authors.forename: Mai
authors.initials: M
authors.lastname: Urikura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Satouchi
authors.forename: Akira
authors.initials: A
authors.lastname: Tokumura
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D008246:Lysophospholipids / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010712:Phosphatidic Acids / Q000378:metabolism / Q000627:therapeutic use*; D054467:Phospholipases A2 / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D013270:Stomach / Q000201:enzymology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008246:Lysophospholipids; D010712:Phosphatidic Acids; D049368:Receptors, Lysophosphatidic Acid; D054467:Phospholipases A2; C032881:lysophosphatidic acid; D001241:Aspirin