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Endotoxin-induced changes in phospholipid dynamics of the stomach
Elizabeth J Dial1, Duy M Tran, Ari Hyman
1Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USA. elizabeth.j.dial@uth.tmc.edu
Background:
The gastric mucosa is protected in part by a hydrophobic layer of phosphatidylcholine (PC) that overlies the mucus gel on the stomach. Endotoxin treatment (i.e., lipopolysaccharide [LPS]) results in an apparent disruption of this layer, as evidenced by a reduction in surface hydrophobicity and an increase in transmural permeability. The current studies compared PC and lyso-PC levels in mucus and gastric mucosa before and after LPS treatment, and examined potential mechanisms for surface phospholipid changes.
Methods:
Rats were administered LPS (5 mg//kg, intraperitoneally) and samples were collected after 5 h for analysis of PC and its primary degradant, lyso-PC, in the loosely and firmly adherent mucus layers and the mucosa. The dependence of LPS-induced effects on gastric alkalinization, PC synthetic activity, and intestinal reflux material was assessed.
Results:
The gastric contents after LPS, which also contained duodenal reflux material, had greatly increased amounts of PC and lyso-PC. The firmly adherent mucus layer was unchanged. The gastric mucosa after LPS revealed significant reductions of PC levels and no change in lyso-PC content. These phospholipid changes were not caused by alkalinization of the stomach or altered PC synthesis. Prevention of duodenogastric reflux by pylorus ligation blocked the LPS-induced increase in luminal lyso-PC and the reduction in mucosal PC.
Conclusions:
LPS appears to induce a release of PC from gastric mucosa into the lumen, along with degradation of PC to lyso-PC, without an effect on PC synthesis. Component(s) of intestinal reflux material appear to be required for these effects. The lowered PC levels in gastric mucosa after LPS may contribute to reduced barrier properties of this tissue.
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