References:
- Dial, E.J., Doyen, J.R., Lichtenberger, L.M., Phospatidylcholine-associated non steroidal anti-inflammtory drugs (NSAIDS) Inhibit DNA synthesis and growth of colon cancer cells. Cance Chemother. Pharmacol. 57:295-300, 2006.
- Dial, E.J., Dohrman, A.J., Romero, J.J., Lichtenberger, L.M. Recombinant human lactoferrin prevents NSAID-induced intestinal bleeding in rodents. J. Pharm. Pharmacol. 57:93-99, 2005.
- Darling. R.L.., Romero, J.J., Dial, E.J., Akunda, J.K., Langenbach, R., Lichtenberger, L.M. Effects of aspirin on gastric mucosal integrity, hydrophobicity and prostaglandins in cyclooxygenase knockout mice. Gastroenterology 127:94-104, 2004.
Lenard M. Lichtenberger, Ph.D.
Professor
UTHSC, Medical School, (713) 500 - 6320
Lenard.M.Lichtenberger@uth.tmc.edu
Mechanism of peptic ulcer disease
The gastrointestinal mucosa is constituted by a population of highly differentiated epithelial cells that have secretary, absorptive and endocrine function. The luminal surface of this polarized epithelial cells, interface with a hostile proteolytic environment that will readily digest dietary nutrients. To prevent autolysis, the gastrointestinal mucosa developed intricate barrier properties that prevent the back – diffusion of luminal acid, bacterial toxins and other agents (e.g. bile salts). This barrier property is compromised in disease states leading to peptic ulcer disease and other erosive diseases of the GI tract. Our laboratory has been studying the surface barrier properties of the stomach in health and disease states both in clinical tissue and in animal models of peptic ulcer disease and colitis. We have determined that the mucus gel later of both the gastric and colonic mucosa have unique hydrophobic or non-wettable properties that protect the underlying tissue from noxious water-soluble agents in the lumen. Furthermore, we have demonstrated that this biophysical property is attributable to the ability of surface mucus cells to biosynthesize and secrete surfactant-like phospholipids that recruit to the air/liquid interface of the mucus gel layer.
We have also demonstrated that this hydrophobic phospholipid later is attenuated in conditions associated with peptic ulcer disease (intake of aspirin and other non-steroidal anti-inflammatory drugs/NSAIDs and infection with Helicobacter pylori in both man and animal models). We are presently utilizing this information to develop strategies to fortify the barrier to treat/prevent peptic ulcer disease.
