Intestinal permeability in the pathogenesis of NSAID-induced enteropathy

Journal of Gastroenterology

Volumn 44, Issue SUPPL. 19, 2009, Pages 23-29

  Bjarnason, Ingvar ^a   Takeuchi, Ken ^b  

^a KING S COLLEGE HOSPITAL   (United Kingdom)

^b Hamamatsu South Hospital   (Japan)

Author keywords

Intestinal inflammation; Intestinal permeability; Intestinal toxicity; NSAIDs

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTIBIOTIC AGENT; CARBOMER; CELECOXIB; CYCLOOXYGENASE 2 INHIBITOR; DICLOFENAC; HISTAMINE H2 RECEPTOR ANTAGONIST; INDOMETACIN; LACTOFERRIN; LUMIRACOXIB; METRONIDAZOLE; MISOPROSTOL; NABUMETONE; NAPROXEN; NICOTINE; NIMESULIDE; NITRIC OXIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN DERIVATIVE; REBAMIPIDE; RECOMBINANT LACTOFERRIN; ROFECOXIB; SALAZOSULFAPYRIDINE; SULINDAC; TRACE ELEMENT; UNCLASSIFIED DRUG;

ARTICLE; DISEASE SEVERITY; DRUG EFFICACY; HUMAN; INTESTINE FLORA; INTESTINE MUCOSA PERMEABILITY; LACTOBACILLUS; MEDLINE; MITOCHONDRIAL RESPIRATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PATHOGENESIS; PRIORITY JOURNAL; SMALL INTESTINE DISEASE; STOMACH PH; STOMACH ULCER;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CYCLOOXYGENASE 2 INHIBITORS; HUMANS; INTESTINAL ABSORPTION; INTESTINAL DISEASES; MICRONUTRIENTS; PERMEABILITY; PROSTAGLANDINS;

EID: 58849111794     PISSN: 09441174     EISSN: 14355922     Source Type: Journal    
DOI: 10.1007/s00535-008-2266-6     Document Type: Article

References (89)

1. Tympner F. Gastroscopic findings after therapy with nonsteroidal anti-inflammatory drugs. J Rheumatol 1981;40:179-181.
2. Roth SH, Bennett RE. Non-steroidal anti-inflammatory drug gastropathy recognition and response. Arch Intern Med 1987;147:2093-2100.
3. Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: Multicenter double blind, placebo-controlled trial. Lancet 1988;ii:1277-1280.
4. Quinn CM, Bjarnason I, Price AB. Gastritis in patients on nonsteroidal anti-inflammatory drugs. Histopathology (Oxf) 1993;23:341-348.
5. Morgan RW. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999;341:1397.
6. Lakari EN, Lacey Smith J, Lidsky MD, Graham DY. Gastroduodenal damage and dyspeptic symptoms in arthritis patients during chronic nonsteroidal anti-inflammatory drug use. Am J Gastroenterol 1987;82:1153-1158.
7. Graham DY, Lidsky MD, Cox AM, Evans DJ, Evans DG, Alpert L, et al. Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection. Gastroenterology 1991;100:1653-1657.
8. Collins AJ, Davies J, Dixon ASJ. Contrasting presentation and findings between patients with rheumatic complaints taking non-steroidal anti-inflammatory drugs and a general population referred to endoscopy. Br J Rheumatol 1986;25:50-53.
9. Walt R. Drug therapy: Misoprostol for the treatment of peptic ulcer and antiinflammatory drug-induced gastroduodenal ulceration. N Engl J Med 1992;327:1575-1580.
10. Ladwa M, Takeuchi K, Bjarnason I. Non-steroidal antiinflammatory drugs request parity with Helicobacter pylori. Scand J Gastroenterol 2006;41:373-375.
11. Bardhan KD, Bjarnason I, Scott DL, Griffin WM, Fenn GC, Shield MJ, et al. The prevention and healing of acute NSAID-associated gastroduodenal mucosal damage by misoprostol. Br J Rheumatol 1993;32:990-995.
12. Hawkey CJ, Laine L, Harper SE, Quan HU, Bolognese JA, Mortensen E. Influence of risk factors on endoscopic and clinical ulcers in patients taking rofecoxib or ibuprofen in two randomized controlled trials. Aliment Pharmacol Ther 2001;15:1593-1601.
13. Bjarnason I, Hayllar J, Macpherson AJ, Russell AS. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine. Gastroenterology 1993;104:1832-1847.
14. Bjarnason I, Zanelli G, Prouse P, Smethurst P, Levi S, Gumpel MJ, et al. Blood and protein loss via small intestinal inflammation induced by nonsteroidal anti-inflammatory drugs. Lancet 1987;2:711-714.
15. Bjarnason I, Zanelli G, Smethurst P, Burke M, Gumpel MJ, Price AB, et al. Clinico-pathological features of nonsteroidal antiinflammatory drug induced small intestinal strictures. Gastroenterology 1988;94:1070-1074.
16. Langman MJS, Morgan L, Worrall A. Use of anti-inflammatory drugs by patients with small or large bowel perforation and haemorrhage. Br Med J 1985;290:347-349.
17. Laine L, Connors LG, Reicin A, Hawkey CJ, Burgos-Vargas R, Schnitzer TJ, et al. Serious lower gastrointestinal clinical events with nonselective NSAID or coxib use. Gastroenterology 2003;124:288-292.
18. Vane JR, Botting RM. Overview: Mechanisms of action of antiinflammatory drugs. In: Vane J, Botting J, Botting R, editors. Improved non-steroidal anti-inflammatory drugs. COX-2 enzyme inhibitors. Dordrecht: Kluwer; 1996. 1-27.
19. Hawkey CJ. COX-2 inhibitors. Lancet 1999;353:307-314.
20. Somasundaram S, Hayllar J, Rafi S, Wrigglesworth J, Macpherson A, Bjarnason I. The biochemical basis of NSAID-induced damage to the gastrointestinal tract: A review and a hypothesis. Scand J Gastroenterol 1995;30:289-299.
21. Scarpignato C. NSAID-induced intestinal damage: Are luminal bacteria the therapeutic target? Gut 2008;57:145-148.
22. Somasundaram S, Macpherson AJ, Hayllar J, Saratchandra P, Bjarnason I. Enterocyte mitochondrial damage due to NSAID in the rat. Gut 1992;33(suppl 1):S5.
23. Somasundaram S, Sadique J. The effect of peripheral inflammation and the action of anti-inflammatories on the intestinal transport of l4 C-leucine in rats. Acta Biol Med Exp 1985;10:35-39.
24. Somasundaram S, Rafi S, Hayllar J, Sigthorsson G, Jacob M, Price AB, et al. Mitochondrial damage: A possible mechanism of the "topical" phase of NSAID-induced injury to the rat intestine. Gut 1997;41:344-353.
25. Somasundaram S, Rafi S, Jacob M, Sigthorsson G, Mahmud T, Sherwood R, et al. Intestinal tolerability of nitroxybutylflurbiprofen in rats. Gut 1997;40:608-613.
26. Somasundaram S, Sigthorsson G, Price AB, Tavares IA, Rafi S, Mahmud T, et al. The relative importance of inhibition of cyclooxygenase and uncoupling of oxidative phosphorylation in the gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2000;14:639-650.
27. Bjarnason I, Macpherson AJM, Hollander D. Intestinal permeability: An overview. Gastroenterology 1995;108:1566-1581.
28. Travis S, Menzies IS. Intestinal permeability: Functional assessment and significance. Clin Sci 1992;82:471-488.
29. Bjarnason I, Takeuchi K, Bjarnason A, Adler SN, Teahon K. The G.U.T. of gut. Scand J Gastroenterol 2004;39:807-815.
30. Robert A, Asano T. Resistance of germ free rats to indomethacin-induced intestinal lesions. Prostaglandins 1977;14:331-341.
31. Melrange R, Moore G, Blower PR, Coates ME, Ward FW, Ronaasen V. A comparison of indomethacin with ibuprofen on gastrointestinal mucosal integrity in conventional and germ free rats. Aliment Pharmacol Ther 1992;6:67-77.
32. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs. Nature (Lond) 1971;231:232-235.
33. Vane JR. Towards a better aspirin. Nature (Lond) 1994;367:215-216.
34. Vane JR. NSAIDs, Cox-2 inhibitors, and the gut. Lancet 1995;346:1105-1106.
35. Langenbach R, Morham SG, Tiano HF, Loftin CD, Ghanayem BI, Chulada PC, et al. Prostaglandin synthase 1 gene disruption in mice reduced arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell 1995;83:483-492.
36. Sigthorsson G, Simpson RJ, Walley M, Anthony A, Foster R, Hotz-Behoftsitz C, et al. COX-1 and 2, intestinal integrity and pathogenesis of NSAID-enteropathy in mice. Gastroenterology 2002;122:1913-1923.
37. Bjarnason I, Scarpignato C, Takeuchi J, Rainsford KD. Determinants of the short-term gastric damage caused by NSAIDs in man. Aliment Pharmacol Ther 2007;26:95-106.
38. Wallace JL, McKnight W, Reuter BK, Vergnolle N. NSAID-induced gastric damage in rats: Requirement for inhibition of both cyclooxygenase 1 and 2. Gastroenterology 2000;119:706-714.
39. Morham SG, Langenbach R, Loftin CD, Tiano HF, Vouloumanos N, Jennette JC, et al. Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell 1995;83:473-482.
40. Maiden L, Thjodleifsson B, Seigal A, Bjarnason II, Scott D, Birgisson S, et al. Long-term effects of nonsteroidal antiinflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: A cross-sectional capsule enteroscopy study. Clin Gastroenterol Hepatol 2007;5:1040-1045.
41. Brune K, Dietzel K, Nurnberg B, Schneider H-T. Recent insight into the mechanism of gastrointestinal tract ulceration. Scand J Rheumatol 1987;Suppl 65:135-140.
42. Brune K, Schwietzer A, Eckert H. Parietal cells of the stomach trap salicylates during absorption. Biochem Pharmacol 1977;26:1735-1740.
43. Gullikson GW, Cline WS, Lorenzson V, Benz L, Olsen WA, Bass P. Effects of anionic surfactants on hamster small intestinal membrane structure and function: Relationship to surface activity. Gastroenterology 1977;73:501-511.
44. Gullikson GW, Sender M, Bass P. Laxative-like effects of nonsteroidal anti-inflammatory drugs on intestinal fluid movement and membrane integrity. J Pharmacol Exp Ther 1981;220:236-252.
45. Lichtenberger LM, Romero JJ, Wang ZM. ASA forms an ionic complex with phosphatidylcholine: Possible molecular explanation for its ulcerogenic action. Gastroenterology 1994;106:A134.
46. Lichtenberger LM, Wang Z-M, Romero JJ, Ulloa C, Perez JC, Giraud M-N, 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.
47. Lichtenberger LM, Graziani LA, Dial EJ, Butler BD, Hills BA. Role of surfact-active phospholipids in gastric cytoprotection. Science 1983;219:1327-1329.
48. 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.
49. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal safety of nonsteroidal antiinflammatory drugs. N Engl J Med 1999;340:1888-1899.
50. 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.
51. Mahmud T, Rafi SS, Scott DL, Wrigglesworth JM, Bjarnason I. Nonsteroidal antiinflammatory drugs and uncoupling of mitochondrial oxidative phosphorylation. Arthritis Rheum 1996;39:1998-2003.
52. Rafi S. Studies on the pathogenesis of NSAID enteropathy, with special reference to mitochondria. PhD thesis. London: University of London. 1999.
53. Hotz-Behofsits C, Walley M, Sigthorsson G, Simpson R, Bjarnasson I. NSAID enteropathy with normal mucosal prostaglandins. Gastroenterology 2004;126 17 Suppl S417.
54. Bjarnason I, Williams P, Smethurst P, Peters TJ, Levi AJ. The effect of NSAIDs and prostaglandins on the permeability of the human small intestine. Gut 1986;27:1292-1297.
55. Bjarnason I, Smethurst P, Menzies IS, Peters TJ. The effect of polyacrylic acid polymers (carbopol) on small intestinal function and permeability changes caused by indomethacin. Scand J Gastroenterol 1991;26:685-688.
56. Bjarnason I, Smethurst P, Macpherson A, Walker F, McElnay JC, Passmore AP, et al. Glucose and citrate reduce the permeability changes caused by indomethacin in humans. Gastroenterology 1992;102:1546-1550.
57. Bjarnason I, Smethurst P, Fenn GC, Lee CF, Menzies IS, Levi AJ. Misoprostol reduces indomethacin induced changes in human small intestinal permeability. Dig Dis Sci 1989;34:407-411.
58. Bjarnason I, Smethurst P, Clarke P, Menzies IS, Levi AJ, Peters TJ. Effect of prostaglandins on indomethacin induced increased intestinal permeability in man. Scand J Gastroenterol 1989;29(suppl 164):97-103.
59. Bjarnason I, Fehilly B, Smethurst P, Menzies IS, Levi AJ. The importance of local versus systemic effects of non-steroidal antiinflammatory drugs to increase intestinal permeability in man. Gut 1991;32:275-277.
60. Bjarnason I, Williams P, So A, Zanelli G, Levi AJ, Gumpel MJ, et al. Intestinal permeability and inflammation in rheumatoid arthritis; effects of non-steroidal anti-inflammatory drugs. Lancet 1984;ii:1171-1174.
61. Sigthorsson G, Tibble J, Hayllar J, Menzies I, Macpherson A, Moots R, et al. Intestinal permeability and inflammation in patients on NSAIDs. Gut 1998;43:506-511.
62. Smecuol E, Bai JC, Sugai E, Vazquez H, Niveloni S, Pedreira S, et al. Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs. Gut 2001;49:650-655.
63. Jenkins AP, Trew DR, Nukajam WS, Crump BJ, Menzies IS, Creamer B. Do nonsteroidal anti-inflammatory drugs increase colonic permeability? Gut 1991;32:66-69.
64. Davies GR, Rampton DS. The pro-drug sulindac may reduce the risk of intestinal damage associated with the use of conventional non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 1991;5:593-598.
65. Davies GR, Wilkie ME, Rampton DS. Effects of metronidazole and misoprostol on indomethacin-induced changes in intestinal permeability. Dig Dis Sci 1993;38:417-425.
66. Aabakken L, Larsen S, Osnes K. Sucralfate for prevention of naproxen-induced mucosal lesions. Scand J Rheumatol 1989;18:361-368.
67. Aabakken L, Osnes M. 51Cr-Ethylenediaminetetraacetic acid absorption test. Effects of naproxen, a non-steroidal, antiinflammatory drug. Scand J Gastroenterol 1990;25:917-924.
68. Aabakken L. 51Cr-Ethylenediaminetetraacetic acid absorption test. Methodological aspects. Scand J Gastroenterol 1989;24:351-358.
69. Aabakken L, Larsen S, Osnes M. Cimetidine tablets or suspension in the prevention of gastrointestinal mucosal lesions caused by nonsteroidal anti-inflammatory drugs. Scand J Rheumatol 1989;18:647-655.
70. Hawkey CJ, Jones IJ, Atherton CT, Slelly MM, Bebb JR, Fagerholm U, et al. Gastrointestinal safety of AZD3582, a cyclooxygenase inhibiting nitric oxide donator: Proof of concept study in humans. Gut 2003;52:1537-1542.
71. Shah AA, Thjodleifsson B, Murray FE, Sigthorsson G, Oddson E, Gudjonsson H, et al. A randomised, double blind, double dummy, crossover study of the effects of nimesulide and naproxen on the gastrointestinal tract and an in vivo assessment of their selectivity for cyclooxygenase 1 and 2. Gut 2001;48:339-348.
72. Hond ED, Hiele M, Peeters M, Ghoos Y, Rutgeers P. Effect of long-term oral glutamine supplements on small intestinal permeability in Crohn's disease. J Parenter Enteral Nutr 1999;23:7-11.
73. Krause MM, Brand MD, Krauss S, Meisel C, Vergin H, Burmester GR, et al. Nonsteroidal antiinflammatory drugs and a selective cyclooxygenase 2 inhibitor uncouple mitochondria in intact cells. Arthritis Rheum 2003;48:1438-1444.
74. Atherton C, Jones J, KcKaig B, Bebb J, Cunliffe R, Burdsall J, et al. Pharmacology and gastrointestinal safety of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor: An integrated study. Clin Gastroenterol Hepatol 2004;2:113-120.
75. Sigthorsson G, Crane R, Simon T, Hoover M, Quan H, Bolognese J, et al. COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: A double blind crossover study comparing rofecoxib with placebo and indomethacin. Gut 2000;47:527-532.
76. Bjarnason I, Peters TJ, Levi AJ. Intestinal permeability: Clinical correlates. Dig Dis 1986;4:83-92.
77. Aabakken L, Bjørnbeth BA, Weberg R, Viksmoen L, Larsen S, Osnes M. NSAID-associated gastroduodenal damage: Does famotidine protection extend into the mid- and distal duodenum? Aliment Pharmacol Ther 1990;4:295-303.
78. Aabakken L, Bjørnbeth BA, Hofstad B, Olaussen B, Larsen S, Osnes M. Comparison of the gastrointestinal side effects of naproxen formulated as plain tablets, enteric-coated tablets, or enteric-coated granules in capsules. Scand J Gastroenterol 1989;163:65-73.
79. Morris AJ, Murray L, Sturrock RD, Madhok R, Capell HA, Mackenzie JF. Short report: The effect of misoprostol on the anaemia of NSAID enteropathy. Aliment Pharmacol Ther 1994;8:343-346.
80. Park SH, Cho CS, Lee OY, Jun JB, Lin SR, Zhou LY, et al. Comparison of prevention of NSAID-induced gastrointestinal complications by rebamipide and misoprostol: A randomized, multicenter, controlled trial-STORM Study. J Clin Biochem Nutr 2007;40:148-155.
81. Bjarnason I, Hayllar J, Smethurst P, Price AB, Menzies IS, Gumpel MJ. Metronidazole reduces inflammation and blood loss in NSAID enteropathy. Gut 1992;33:1204-1208.
82. Hayllar J, Price AB, Smith T, Macpherson A, Gumpel MJ, Bjarnason I. Nonsteroidal antiinflammatory drug-induced small intestinal inflammation and blood loss: Effect of sulphasalazine and other disease modifying drugs. Arthritis Rheum 1994;37:1146-1150.
83. Gotteland M, Cruchet S, Verbeke S. Effect of Lactobacillus ingestion on the gastrointestinal mucosal barrier alterations induced by indometacin in humans. Aliment Pharmacol Ther 2001;15(1):11-17.
84. Playford RJ, MacDonald CE, Calnan DP, Floyd DN, Podas T, Johnson W, et al. Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal antiinflammatory drug-induced increase in intestinal permeability. Clin Sci 2001;100:627-633.
85. Hawkey CJ. Future treatments for arthritis: New NSAIDs, NO NSAIDs, or no NSAIDs? Gastroenterology 1995;109:614-616.
86. Bours MJ, Bos HJ, Meddings JB, Brummer RJ, van den Brandt PA, Dagnelie PC. Effects of oral adenosine 5′-triphosphate and adenosine in enteric-coated capsules on indomethacin-induced permeability changes in the human small intestine: A randomized cross-over study. BMC Gastroenterol 2007;7:23.
87. Leite AZ, Sipahi AM, Damião AO, Coelho AM, Garcez AT, Machado MC, et al. Protective effect of metronidazole on uncoupling mitochondrial oxidative phosphorylation induced by NSAID: A new mechanism. Gut 2001;48:163-167.
88. Suenaert P, Bulteel V, Den Hond E, Geypens B, Monsuur F, Luypaerts A, et al. In vivo influence of nicotine on human basal and NSAID-induced gut barrier function. Scand J Gastroenterol 2003;38:399-408.
89. Troost FJ, Saris WH, Brummer RJ. Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers. Eur J Clin Nutr 2003;57:1579-1585.