- Dial EJ, Tran DM, Hyman A, Lichtenberger LM. (2012) Endotoxin-induced changes in phospholipid dynamics of the stomach. J Sug Res 30: 1-7.
- Lichtenberger LM, Zhou Y, Jayaraman V, Doyen JR, O’Neil RG, Dial EJ, Volk DE, Gorenstein DG, Boggara MB, Krishnamoorti R. (2012) Insight into NSAID-induced membrane alterations: pathogenesis and therapeutics: Characterization of interaction of NSAIDs with phosphatiylcholine. Biochim Biophysica Acta 1821: 994-1002.
- Lim YJ, Dial EJ, Lichtenberger LM. (2012) Advent of novel phosphatidylcholine-associated nonsteroidal antiinflammatory drugs with improved gastrointestinal safety. Gut and Liver (Nov 2).
- Lim YJ, Phan TM, Dial EJ, Graham DY, Lichtenberger LM. (2012) In vitro and in vivo protection against indomethacin-induced small intestinal injury by proton pump inhibitors, acid pump antagonists or Indomethacin-phosphatidylcholine. Digestion 86: 171-177.
- Prakash P, Sayyed-Ahmad A, Zhou Y, Volk DE, Gorenstein DG, Dial EJ, Lichtenberger LM, Gorfe AA. (2012) Aggregation behanvior of ibuprofen, cholic acid and didecylphosphatidylcholine micelles. Biochim Biophysica Acta 1818: 3040-3047.
- Cryer B, Bhatt DL, Lanza FL, Dong J-F, Lichtenberger LM, Marathi UK. (2011) Low dose aspirin induced ulceration is attenuated by Aspirin-Phosphatidylcholine: A randomized clinical trial. Amer J Gastro 106: 272-277.
- Lichtenberger LM, Phan T, Okabe S. (2011) Aspirin’s ability to induce intestinal injury is dependent on bile and can be reversed of pre-associated with phosphatidylcholine. J Physiol Pharmacol 62: 491-496.
- Sayyed-Ahmad, A, Lichtenberger, LM and Gorfe, AA. (2010) Structure and Dynamics of Cholic Acid and Dodecylphosphocholine−Cholic Acid Aggregates. Langmuir 26, 13407-13414.
- Cryer B, Bhatt DL, Lanza FL, Dong J-F, Lichtenberger LM, Marathi UK. (2010). Low dose aspirin induced ulceration is attenuated by Aspirin-Phosphaidylcholine: A randomized clinical trial. Amer J Gastro 16 Nov [Epub ahead of print].
- Darkoh C, Lichtenberger LM, Ajami N, Dial EJ, Jiang Z-D and Dupont HL. (2010). Bile acids improve the antimicrobial effect of Rifaximin. Antimicrobial Agents Chemotherapy 54, 3618-3624.
- Dial EJ, Tran DM, Romero JJ, Zayat M and Lichtenberger LM. (2010). A direct role for secretory phospholipase A2 and lysophosphatidylcholine in the mediation of LPS induced gastric injury. Shock 33, 634-8.
- Zhou Y, Dial EJ, Doyen R and Lichtenberger LM. (2010). Effect of indomethacin on bile acid-phospholipid interactions: implication for small intestinal injury induced by nonsteroidal anti-inflammatory drugs. Am J Physiol Gastrointest Liver Physiol 298, G722-G731.
- Zhou Y, Hancock JF and Lichtenberger L. (2010). Nonsteroidal anti-inflammatory drug indomethacin induces phase heterogeneity in mixed lipid membranes: potential implication for its diverse biological actions. PLoS One 5, e8811.
- Zhou Y, Lichtenberger L and Hancock JF. (2010). The anti-inflammatory drug indomethacin alters nanoclustering in synthetic and cell plasma membranes. J Biol Chem 285, 35188-35195.
- Zhou Y, Doyen R, Lichtenberger LM. The role of membrane cholesterol in determining bile acid cytotoxicity and cytoprotection of ursodeoxycholic acid. Biochim Biophys Acta, 1788, 507-527 (2009).
- Lichtenberger LM, Romero, JJ, Dial EJ, Moore JE. Naproxen-PC: a GI safe and highly effective anti-inflammatory. Inflammopharmacology 16: 1-5 (2009).
- Lichtenberger LM, Romero JJ, Dial EJ. Evaluation of the GI safety and therapeutic efficacy of parenterally administered phosphatidylcholine-associated indomethacin in rodent model systems. Brit J Pharmacol, 157, 252-7(2009).
- Dial EJ, Tran DM, Romero JJ, Zayat M, Lichtenberger LM. A direct role of secretory phospholipase A2 and lysophosphatidylcholine in the mediation of lipopolysaccharide-induce gastric injury. Shock, [Nov 20 Epub ahead of print] (2009).
- Dial EJ, Darling RL, Lichtenberger LM. Importance of biliary excretion of indomethacin in gastrointestinal and hepatic injury. J Gastroenterol Hepatol in press: 2008
- Dial EJ, Rooijakkers SH, Darling RL, Romero JJ, Lichtenberger LM. Role of phosphatidylcholine saturation in preventing bile salt toxicity to gastrointestinal epithelia and membranes. J Gastroenterol Hepatol in press: 2008.
- Doyen JR, Yucer N, Lichtenberger LM, Kulmacz RJ. Phospholipid actions on PGHS-1 and -2 cyclooxygenase kinetics. Prostaglandins & other Lipid Mediators in press: 2008.
- Lichtenberger LM, Zhou Y, Dial EJ, Raphael RM. NSAID injury to the gastrointestinal tract: Evidence that NSAIDs interact with phospholipids to weaken the hydrophobic surface barrier and induce the formation of unstable pores in membranes. J Pharm Pharmacol 58: 1421-1428, 2007.
- Lichtenberger LM, Romero JJ, Dial EJ. Surface phospholipids in gastric injury and protection when a selective cyclooxygenase-2 inhibitor (coxib) is used in combination with aspirin. Br J Pharmacol 150:913-919, 2007.
- Dial EJ, Doyen JR, Lichtenberger LM, Phosphatidylcholine-associated non steroidal anti-inflammtory drugs (NSAIDS) Inhibit DNA synthesis and growth of colon cancer cells. Cancer Chemother Pharmacol 57:295-300, 2006.
- Darling RL, Romero JJ, Dial EJ, Akunda JK, Langenbach R, Lichtenberger LM. Effects of aspirin on gastric mucosal integrity, hydrophobicity and prostaglandins in cyclooxygenase knockout mice. Gastroenterology 127:94-104, 2004
Lenard M. Lichtenberger, Ph.D.
UTHSC, Medical School, (713) 500 - 6320
Mechanism of GI ulcer disease
The gastrointestinal (GI) mucosa is constituted by a population of highly differentiated epithelial cells that have secretary, absorptive and endocrine function. The luminal surface of these polarized epithelial cells, interfaces with a hostile proteolytic environment that will readily digest dietary nutrients. To prevent autolysis, the GI 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 layer 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 layer 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) and colitis 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 and inflammatory bowel disease. A start-up company, PLx Pharma Inc. (http://www.plxpharma.com/) was formed in 2003 to commercialize a novel class of NSAIDs that have been pre-associated with soy phospholipids to reduce the drugs’ GI toxicity.