Advent of novel phosphatidylcholine-associated nonsteroidal anti-inflammatory drugs with improved gastrointestinal safety

Gut and Liver

Volumn 7, Issue 1, 2013, Pages 7-15

  Lim, Yun Jeong ^a,b   Dial, Elizabeth J ^b   Lichtenberger, Lenard M ^b  

^a Dongguk University   (South Korea)

^b UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

Bile; Non steroidal anti inflammatory agents; Phosphatidylcholines; Phospholipids

Indexed keywords

ACETYLSALICYLIC ACID; AMPHOPHILE; BILE SALT; CELECOXIB; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITOR; DEOXYCHOLIC ACID; FAMOTIDINE; GLYCODEOXYCHOLIC ACID; HISTAMINE H2 RECEPTOR ANTAGONIST; IBUPROFEN; INDOMETACIN; MEMBRANE PHOSPHOLIPID; NONSTEROID ANTIINFLAMMATORY AGENT; OMEPRAZOLE; PHOSPHATIDYLCHOLINE; PL 1100; PL 2200; PROSTAGLANDIN; PROSTAGLANDIN E2; PROTON PUMP INHIBITOR; RANITIDINE; TAURODEOXYCHOLIC ACID; UNCLASSIFIED DRUG;

BILE ACID SYNTHESIS; BILE DUCT LIGATION; BILE SECRETION; BLOOD VESSEL PERMEABILITY; CYTOTOXICITY; DIGESTIVE SYSTEM INJURY; DRUG ABSORPTION; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG FORMULATION; DRUG SAFETY; ENTERIC COATED TABLET; ENTEROHEPATIC CIRCULATION; ENZYME INHIBITION; GASTROINTESTINAL MUCOSA; HEMOLYSIS; HUMAN; HYDROPHOBICITY; INTESTINE INJURY; MICELLE; NONHUMAN; OSTEOARTHRITIS; PHOSPHOLIPID BILAYER; PROSTAGLANDIN SYNTHESIS INHIBITION; PROTECTION; REVIEW; SMALL INTESTINE PERFORATION; STOMACH HEMORRHAGE; STOMACH INJURY; STOMACH ULCER; ULCER HEALING; ULCEROGENESIS;

EID: 84875092945     PISSN: 19762283     EISSN: None     Source Type: Journal    
DOI: 10.5009/gnl.2013.7.1.7     Document Type: Review

References (64)

1. Scarpignato C, Hunt RH. Nonsteroidal antiinflammatory drug-related injury to the gastrointestinal tract: clinical picture, pathogenesis, and prevention. Gastroenterol Clin North Am 2010;39:433-464.
2. Watson DJ, Harper SE, Zhao PL, Quan H, Bolognese JA, Simon TJ. Gastrointestinal tolerability of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib compared with nonselective COX-1 and COX-2 inhibitors in osteoarthritis. Arch Intern Med 2000;160:2998-3003.
3. Lichtenberger LM, Wang ZM, Romero JJ, et al. Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospholipids: insight into the mechanism and reversal of NSAID-induced gastrointestinal injury. Nat Med 1995;1:154-158.
4. Lichtenberger LM. The hydrophobic barrier properties of gastrointestinal mucus. Annu Rev Physiol 1995;57:565-583.
5. Lichtenberger LM. Where is the evidence that cyclooxygenase inhibition is the primary cause of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal injury? Topical injury revisited. Biochem Pharmacol 2001;61:631-637.
6. Lichtenberger LM, Romero JJ, Gibson GW, Blank MA. Effect of bisphosphonates on surface hydrophobicity and phosphatidylcholine concentration of rodent gastric mucosa. Dig Dis Sci 2000;45:1792-1801.
7. Barrios JM, Lichtenberger LM. Role of biliary phosphatidylcholine in bile acid protection and NSAID injury of the ileal mucosa in rats. Gastroenterology 2000;118:1179-1186.
8. Giraud MN, Motta C, Romero JJ, Bommelaer G, Lichtenberger LM. Interaction of indomethacin and naproxen with gastric surface-active phospholipids: a possible mechanism for the gastric toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs). Biochem Pharmacol 1999;57:247-254.
9. Lichtenberger LM, Ulloa C, Romero JJ, Vanous AL, Illich PA, Dial EJ. Nonsteroidal anti-inflammatory drug and phospholipid prodrugs: combination therapy with antisecretory agents in rats. Gastroenterology 1996;111:990-995.
10. Lichtenberger LM, Zhou Y, Jayaraman V, et al. Insight into NSAID-induced membrane alterations, pathogenesis and therapeutics: characterization of interaction of NSAIDs with phosphatidylcholine. Biochim Biophys Acta 2012;1821:994-1002.
11. Kao YC, Lichtenberger LM. Localization of phospholipid-rich zones in rat gastric mucosa: possible origin of a protective hydrophobic luminal lining. J Histochem Cytochem 1987;35:1285-1298.
12. Anand BS, Romero JJ, Sanduja SK, Lichtenberger LM. Phospholipid association reduces the gastric mucosal toxicity of aspirin in human subjects. Am J Gastroenterol 1999;94:1818-1822.
13. Lanza FL, Marathi UK, Anand BS, Lichtenberger LM. Clinical trial: comparison of ibuprofen-phosphatidylcholine and ibuprofen on the gastrointestinal safety and analgesic efficacy in osteoarthritic patients. Aliment Pharmacol Ther 2008;28:431-442.
14. Lichtenberger LM. Gastroduodenal mucosal defense. Curr Opin Gastroenterol 1999;15:463-472.
15. Kao YC, Goddard PJ, Lichtenberger LM. Morphological effects of aspirin and prostaglandin on the canine gastric mucosal surface. Analysis with a phospholipid-selective cytochemical stain. Gastroenterology 1990;98:592-606.
16. Goddard PJ, Kao YC, Lichtenberger LM. Luminal surface hydrophobicity of canine gastric mucosa is dependent on a surface mucous gel. Gastroenterology 1990;98:361-370.
17. Dial EJ, Lichtenberger LM. Surface hydrophobicity of the gastric mucosa in the developing rat. Effects of corticosteroids, thyroxine, and prostaglandin E2. Gastroenterology 1988;94:57-61.
18. Kao YC, Lichtenberger LM. Phospholipid- and neutral lipid-containing organelles of rat gastroduodenal mucous cells. Possible origin of the hydrophobic mucosal lining. Gastroenterology 1991;101:7-21.
19. Lichtenberger LM, Romero JJ, Kao YC, Dial EJ. Gastric protective activity of mixtures of saturated polar and neutral lipids in rats. Gastroenterology 1990;99:311-326.
20. Kao YC, Lichtenberger LM. A method to preserve extracellular surfactant-like phospholipids on the luminal surface of rodent gastric mucosa. J Histochem Cytochem 1990;38:427-431.
21. Ottlecz A, Romero JJ, Lichtenberger LM. Helicobacter infection and phospholipase A2 enzymes: effect of Helicobacter felis-infection on the expression and activity of sPLA2 enzymes in mouse stomach. Mol Cell Biochem 2001;221:71-77.
22. Lichtenberger LM, Dial EJ, Ottlecz A, Romero JJ, Lechago J, Fox JG. Attenuation of hydrophobic phospholipid barrier is an early event in Helicobacter felis-induced gastritis in mice. Dig Dis Sci 1999;44:108-115.
23. Giraud MN, Sanduja SK, Felder TB, Illich PA, Dial EJ, Lichtenberger LM. Effect of omeprazole on the bioavailability of unmodified and phospholipid-complexed aspirin in rats. Aliment Pharmacol Ther 1997;11:899-906.
24. Serna JH, Genta RM, Lichtenberger LM, Graham DY, el-Zaatari FA. Invasive Helicobacter-like organisms in feline gastric mucosa. Helicobacter 1997;2:40-43.
25. Lichtenberger LM, Romero JJ. Effect of ammonium ion on the hydrophobic and barrier properties of the gastric mucus gel layer: implications on the role of ammonium in H. pylori-induced gastritis. J Gastroenterol Hepatol 1994;9 Suppl 1:S13-S19.
26. Ottlecz A, Romero JJ, Hazell SL, Graham DY, Lichtenberger LM. Phospholipase activity of Helicobacter pylori and its inhibition by bismuth salts. Biochemical and biophysical studies. Dig Dis Sci 1993;38:2071-2080.
27. Go MF, Lew GM, Lichtenberger LM, Genta RM, Graham DY. Gastric mucosal hydrophobicity and Helicobacter pylori: response to antimicrobial therapy. Am J Gastroenterol 1993;88:1362-1365.
28. Dial EJ, Tran DM, Romero JJ, Zayat M, Lichtenberger LM. A direct role for secretory phospholipase A2 and lysophosphatidylcholine in the mediation of LPS-induced gastric injury. Shock 2010;33:634-638.
29. Dial EJ, Zayat M, Lopez-Storey M, Tran D, Lichtenberger L. Oral phosphatidylcholine preserves the gastrointestinal mucosal barrier during LPS-induced inflammation. Shock 2008;30:729-733.
30. Zayat M, Lichtenberger LM, Dial EJ. Pathophysiology of LPS-induced gastrointestinal injury in the rat: role of secretory phospholipase A2. Shock 2008;30:206-211.
31. Dial EJ, Romero JJ, Villa X, Mercer DW, Lichtenberger LM. Lipopolysaccharide-induced gastrointestinal injury in rats: role of surface hydrophobicity and bile salts. Shock 2002;17:77-80.
32. 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 2008;23:430-436.
33. Schmitz MG, Renooij W. Phospholipids from rat, human, and canine gastric mucosa. Composition and metabolism of molecular classes of phosphatidylcholine. Gastroenterology 1990;99:1292-1296.
34. Zhou Y, Doyen R, Lichtenberger LM. The role of membrane cholesterol in determining bile acid cytotoxicity and cytoprotection of ursodeoxycholic acid. Biochim Biophys Acta 2009;1788:507-513.
35. Dial EJ, Darling RL, Lichtenberger LM. Importance of biliary excretion of indomethacin in gastrointestinal and hepatic injury. J Gastroenterol Hepatol 2008;23(8 Pt 2):e384-e389.
36. Zhou Y, Dial EJ, Doyen R, Lichtenberger LM. 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 2010;298:G722-G731.
37. Graham DY, Opekun AR, Willingham FF, Qureshi WA. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol 2005;3:55-59.
38. Maiden L, Thjodleifsson B, Theodors A, Gonzalez J, Bjarnason I. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology 2005;128:1172-1178.
39. Lanas A, Sopena F. Nonsteroidal anti-inflammatory drugs and lower gastrointestinal complications. Gastroenterol Clin North Am 2009;38:333-352.
40. Bjarnason I, Hayllar J, MacPherson AJ, Russell AS. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 1993;104:1832-1847.
41. Wallace JL, Syer S, Denou E, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology 2011;141:1314-1322.
42. Watanabe T, Higuchi K, Kobata A, et al. Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent. Gut 2008;57:181-187.
43. Lichtenberger LM, Phan T, Okabe S. Aspirin's ability to induce intestinal injury in rats is dependent on bile and can be reversed if pre-associated with phosphatidylcholine. J Physiol Pharmacol 2011;62:491-496.
44. 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 2006;58:1421-1428.
45. Zhou Y, Plowman SJ, Lichtenberger LM, Hancock JF. The anti-inflammatory drug indomethacin alters nanoclustering in synthetic and cell plasma membranes. J Biol Chem 2010;285:35188-35195.
46. Zhou Y, Hancock JF, Lichtenberger LM. The nonsteroidal anti-inflammatory drug indomethacin induces heterogeneity in lipid membranes: potential implication for its diverse biological action. PLoS One 2010;5:e8811.
47. Lichtenberger LM, Barron M, Marathi U. Association of phosphatidylcholine and NSAIDs as a novel strategy to reduce gastrointestinal toxicity. Drugs Today (Barc) 2009;45:877-890.
48. Yamada T, Hoshino M, Hayakawa T, et al. Bile secretion in rats with indomethacin-induced intestinal inflammation. Am J Physiol 1996;270(5 Pt 1):G804-G812.
49. Cryer B, Bhatt DL, Lanza FL, Dong JF, Lichtenberger LM, Marathi UK. Low-dose aspirin-induced ulceration is attenuated by aspirin- phosphatidylcholine: a randomized clinical trial. Am J Gastroenterol 2011;106:272-277.
50. Lichtenberger LM, Romero JJ, Dial EJ. Gastrointestinal safety and therapeutic efficacy of parenterally administered phosphatidylcholine-associated indomethacin in rodent model systems. Br J Pharmacol 2009;157:252-257.
51. Lichtenberger LM, Ulloa C, Vanous AL, et al. Zwitterionic phospholipids enhance aspirin's therapeutic activity, as demonstrated in rodent model systems. J Pharmacol Exp Ther 1996;277:1221-1227.
52. Kurinets A, Lichtenberger LM. Phosphatidylcholine-associated aspirin accelerates healing of gastric ulcers in rats. Dig Dis Sci 1998;43:786-790.
53. Lichtenberger LM, Romero JJ, Dial EJ, Moore JE. Naproxen-PC: a GI safe and highly effective anti-inflammatory. Inflammopharmacology 2009;17:1-5.
54. Billiau A, Matthys P. Modes of action of Freund's adjuvants in experimental models of autoimmune diseases. J Leukoc Biol 2001;70:849-860.
55. Lichtenberger LM, Romero JJ, de Ruijter WM, et al. Phosphatidylcholine association increases the anti-inflammatory and analgesic activity of ibuprofen in acute and chronic rodent models of joint inflammation: relationship to alterations in bioavailability and cyclooxygenase-inhibitory potency. J Pharmacol Exp Ther 2001;298:279-287.
56. Wallace JL, Ferraz JG. New pharmacologic therapies in gastrointestinal disease. Gastroenterol Clin North Am 2010;39:709-720.
57. Scheiman JM. Prevention of damage induced by aspirin in the GI tract. Best Pract Res Clin Gastroenterol 2012;26:153-162.
58. Darling RL, Romero JJ, Dial EJ, Akunda JK, Langenbach R, Lichtenberger LM. The effects of aspirin on gastric mucosal integrity, surface hydrophobicity, and prostaglandin metabolism in cyclooxygenase knockout mice. Gastroenterology 2004;127:94-104.
59. Laine L, Maller ES, Yu C, Quan H, Simon T. Ulcer formation with low-dose enteric-coated aspirin and the effect of COX-2 selective inhibition: a double-blind trial. Gastroenterology 2004;127:395-402.
60. 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 2007;150:913-919.
61. Mizuno H, Sakamoto C, Matsuda K, et al. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology 1997;112:387-397.
62. Schmassmann A, Zoidl G, Peskar BM, et al. Role of the different isoforms of cyclooxygenase and nitric oxide synthase during gastric ulcer healing in cyclooxygenase-1 and -2 knockout mice. Am J Physiol Gastrointest Liver Physiol 2006;290:G747-G756.
63. Rahme E, Bernatsky S. NSAIDs and risk of lower gastrointestinal bleeding. Lancet 2010;376:146-148.
64. Hackelsberger A, Platzer U, Nilius M, et al. Age and Helicobacter pylori decrease gastric mucosal surface hydrophobicity independently. Gut 1998;43:465-469.