Энтеропатия, ассоциированная с применением нестероидных противовоспалительных препаратов (НПВП-энтеропатия)

1. Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects ofnon-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24:121-32. doi: 10.1016/j.bpg.2009.11.005
2. Ливзан М.А., Лялюкова Е.А., Костенко М.Б. Нестероидные противовоспалительные препараты: оценка рисков и пути повышения безопасности терапии. Лечащий врач. 2016;(5):78-82 [Livzan MA, Lyalyukova EA, Kostenko MB. Non-steroid anti-inflammatory preparations: risk assessment and ways of the therapy safety enhancement. Lechashchiy Vrach. 2016;(5):78-82 (In Russ.)].
3. Шостак Н.А., Рябкова А.А., Савельев В.С., Малярова Л.Н. Желудочно-кишечное кровотечение как осложнение гастропатий, связанных с приемом нестероидных противовоспалительных препаратов. Терапевтический архив. 2003;75(5):70-4 [Shostak NA, Ryabkova AA, Savelyev VS, Malyarova LP. Gastrointestinal hemorrhages as complications of gastropathies associated with intake of nonsteroid anti-inflammatory drugs. Therapeutic Archive. 2003;75(5):70-4 (In Russ.)].
4. Montalto M, Gallo A, Gasbarrini A, Landolfi R. NSAID enteropathy: could probiotics prevent it? J Gastroenterol. 2013;48:689-97. doi: 10.1007/s00535-012-0648-2
5. Maiden L. Capsule endoscopic diagnosis of nonsteroidal anti-inflammatory drug-induced enteropathy. J Gastroenterol. 2009;19:64-71. doi: 10.1007/s00535-008-2248-8
6. Свистунов А.А., Осадчук М.А., Киреева Н.В., Хударова А.А., Ачкасов Е.Е. НПВП-индуцированная энтеропатия: современное состояние проблемы. Терапевтический архив. 2018;90(8):95-100 [Svistunov AA, Osadchuk MA, Kireeva NV, Hudarova AA, Achkasov EE. NSAID-induced enteropathy: the current state of the problem. Therapeutic Archive. 2018;90(8):95-100 (In Russ.)]. doi: 10.26442/terarkh201890895-100
7. Graham DY, Opekun AR, Willingham FF, Qureshi WA. Visiblesmall-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol. 2005;3:55-9. 
8. Zeino Z, Sisson G, Bjarnason I. Adverse effects of drugs on small intestine and colon. Best Pract Res Clin Gastroenterol. 2010;24:133-41. doi: 10.1016/j.bpg.2010.02.008
9. Gallo A, Passaro G, Gasbarrini A, Landolfi R, Montalto M. Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate. World J Gastroenterol. 2016;22(32):7186-202. doi: 10.3748/wjg.v22.i32.7186
10. Shimada S, Tanigawa T, Watanabe T, Nakata A, Sugimura N, Itani S, et al. Involvement of gliadin, a component of wheat gluten, in increased intestinal permeability leading to non-steroidal anti-inflammatory drug-induced small-intestinal damage. PLoS One. 2019;14(2):e0211436. doi: 10.1371/journal.pone.0211436. eCollection 2019.
11. Otani K, Tanigawa T, Watanabe T, Shimada S, Nadatani Y, Tanaka F, et al. Microbiota plays a key role in non-steroidal anti-inflammatory drug-induced small intestinal damage. Digestion. 2017;95:22-8. doi: 10.1159/000452356
12. Парфенов А.И., Белостоцкий Н.И., Хомерики С.Г., Ахмадуллина О.В., Быкова С.В. Сабельникова Е.А., Дбар С.Р. Ребамипид повышает активность дисахаридаз у больных энтеропатией с нарушением мембранного пищеварения. Пилотное исследование. Терапевтический архив. 2019;91(2):25-31 [Parfenov AI, Belostotsky NI, Khomeriki SG, Akhmadullina OV, Bykova SV, Sabelnikova EA, Dbar SR. Rebamipide increases the disaccharidases activity in patients with enteropathy with impaired membrane digestion. Pilot study. Therapeutic Archive. 2019;91(2):25-31 (In Russ.)]. doi: 10.26442/00403660.2019.02.000123
13. Robert A, Asano T. Resistance of germfree rats to indomethacin-induced intestinal lesions. Prostaglandins. 1977;14(2):333-41. 
14. Uejima M, Kinouchi T, Kataoka K, Hiraoka I, Ohnishi Y. Role of intestinal bacteria in ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug. Microbiol Immunol. 1996;40:553-60. 
15. Konaka A, Kato S, Tanaka A, Kunikata T, Korolkiewicz R, Takeuchi K. Roles of enterobacteria, nitric oxide and neutrophil in pathogenesis of indomethacin-induced small intestinal lesions in rats. Pharmacol Res. 1999;40(6):517-24. doi: 10.1006/phrs.1999.0550
16. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R: Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57(6):1470-81. doi: 10,2337/DB07-1403
17. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022-3. doi: 10.1038/4441022a
18. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482(7384):179-85. doi: 10.1038/nature10809
19. Donaldson RM Jr. Normal bacterial populations of the intestine and their relation to intestinal function. N Engl J Med. 1964;270:1050-6. doi: 10.1056/NEJM196405142702007
20. Muraki M, Fujiwara Y, Machida H, Okazaki H, Sogawa M, Yamagami H, et al. Role of small intestinal bacterial overgrowth in severe small intestinal damage in chronic non-steroidal anti-inflammatory drug users. Scand J Gastroenterol. 2014;49(3):267-73. doi: 10.3109/00365521.2014.880182
21. Wallace JL, Syer S, Denou E, de Palma G, Vong L, McKnight W, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology. 2011;141(4):1314-22, e1-5. doi: 10.1053/j.gastro.2011.06.075
22. Watanabe T, Tanigawa T, Nadatani Y, Nagami Y, Sugimori S, Okazaki H, et al. Risk factors for severe nonsteroidal anti-inflammatory drug-induced small intestinal damage. Dig Liver Dis. 2013;45(5):390-5. doi: 10.1016/j.dld.2012.12.005
23. Endo H, Sakai E, Taniguchi L, Kessoku T, Komiya Y, Ezuka A, et al. Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users: data from a prospective multicenter capsule endoscopy registry. Gastrointest Endosc. 2014;80(5):826-34. doi: 10.1016/j.gie.2014.03.024
24. Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11(5):483-90. doi: 10.1016/j.cgh.2012.12.011
25. Higuchi K, Umegaki E, Watanabe T, Yoda Y, Morita E, Murano M, et al. Present status and strategy of NSAIDs-induced smallbowel injury. J Gastroenterol. 2009;44(9):879-88. doi: 10.1007/s00535-009-0102-2
26. Somasundaram S, Hayllar H, Rafi S, Wrigglesworth JM, Macpherson AJ, Bjarnason I. The biochemical basis of non-steroidalanti-inflammatory drug-induced damage to the gastrointestinaltract: a review and a hypothesis. Scand J Gastroenterol. 1995;30(4):289-99. doi: 10.3109/00365529509093280
27. Petruzzelli M, Vacca M, Moschetta A, CinziaSasso R, PalascianoG, van Erpecum KJ, et al. Intestinal mucosal damage causedby non-steroidal anti-inflammatory drugs: role of bile salts. ClinBiochem. 2007;40(8):503-10. doi: 10.1016/j.clinbiochem.2007.01.015
28. Watanabe T, Tanigawa T, Nadatani Y, Otani K, Machida H, Okazaki H, et al. Mitochondrial disorders in NSAIDs-induced small bowel injury. J Clin Biochem Nutr. 2011;48(2):117-21. 
29. Wallace JL. Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy. World J Gastroenterol. 2013;19(12):1861-76. doi: 10.3748/wjg.v19.i12.1861
30. Adebayo D, Bjarnason I. Is non-steroidal anti-inflammatory drug (NSAID) enteropathy clinically more important than NSAID gastropathy? Postgrad Med J. 2006;82(965):186-91. doi: 10.1136/pgmj.2005.039586
31. Ливзан М.А., Осипенко М.Ф., Лялюкова Е.А. Поражение органов пищеварения у пациентов, принимающих нестероидные противовоспалительные препараты: факторы риска, тактика ведения. Лечащий врач. 2013;(7):27-34 [Livzan MA, Osipenko MF, Lyalyukova EA. Affection of digestion organs in patients taking non steroid antipyretic preparations: the factors of risk, strategy of conducting the patients. Lechashchiy Vrach. 2013;(7):27-34 (In Russ.)]. Available at: https://www.lvrach.ru/2013/07/15435749/
32. Вахрушев Я.М., Загребина E.A. Энтеропатия, индуцированная нестероидными противовоспалительными препаратами (патогенез, диагностика, лечение). Терапевтический архив. 2012;84(5):74-9 [Vakhrushev YaM, Zagrebina EA. Enteropathy induced by nonsteroid anti-inflammatory drugs: pathogenesis, diagnosis, treatment. Terapeutic Archive. 2012;84(5):74-9 (In Russ.)]. 
33. Fujimori S, Seo T, Gudis K, Ehara A, Kobayashi T, Mitsui K, et al. Prevention of nonsteroidal anti-inflammatory drug-induced small-intestinal injury by prostaglandin: a pilot randomized controlled trial evaluated by capsule endoscopy. Gastrointest Endosc. 2009;69(7):1339-46. doi: 10.1016/j.gie.2008.08.017
34. Niwa Y, Nakamura M, Ohmiya N, Maeda O, Ando T, Itoh A, et al. Efficacy of rebamipide for diclofenac-induced small-intestinal mucosal injuries in healthy subjects: a prospective, randomized, double-blinded, placebo-controlled, cross-over study. J Gastroenterol. 2008;43(2):270-6. doi: 10.1007/s00535-007-2155-4
35. Mizukami K, Murakami K, Abe T, Inoue K, Uchida M, Okimoto T, et al. Aspirin-induced small bowel injuries and the preventive effect of rebamipide. World J Gastroenterol. 2011;17(46):5117-22. doi: 10.3748/wjg.v17.i46.5117
36. Fujimori S, Takahashi Y, Gudis K, Seo T, Ehara A, Kobayashi T, et al. Rebamipide has the potential to reduce the intensity of NSAID-induced small intestinal injury: a double-blind, randomized, controlled trial evaluated by capsule endoscopy. J Gastroenterol. 2011;46(1):57-64. doi: 10.1007/s00535-010-0332-3
37. Lanas A, Scarpignato C. Microbial flora in NSAID-induced intestinal damage: a role for antibiotics? Digestion. 2006;73(1):136-50. doi: 10.1159/000089789
38. Davies GR, Wilkie ME, Rampton DS. Effects of metronidazole and misoprostol on indomethacin-induced changes in intestinal permeability. Dig Dis Sci. 1993;38(3):417-25. doi: 10.1007/bf01316493
39. Bjarnason I, Hayllar J, Smethurst P, Price A, Gumpel MJ. Metronidazole reduces intestinal inflammation and blood loss in nonsteroidal anti-inflammatory drug induced enteropathy. Gut. 1992;33(9):1204-8. doi: 10.1136/gut.33.9.1204
40. Reuter BK, Davles NM, Wallace JL. Nonsteroidal anti-inflammatory drug enteropathy in rats: role of permeability, bacteria, and enterohepatic circulation. Gastroenterology. 1997;112(1):109-17. doi: 10.1016/s0016-5085(97)70225-7
41. Hagiwara M, Kataoka K, Arimochi H, Kuwahara T, Ohnishi Y. Role of unbalanced growth of gram-negative bacteria in ileal ulcer formation in rats treated with a nonsteroidal anti-inflammatory drug. J Med Invest. 2004;51(1-2):43-51. 
42. Watanabe T, Higuchi K, Kobata A, Nishio H, Tanigawa T, Shiba M, et al. Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent. Gut. 2008;57(2):181-7. doi: 10.1136/gut.2007.125963 
43. Scarpignato C. NSAID-induced intestinal damage: are luminal bacteria the therapeutic target? Gut. 2008;57(2):145-8. doi: 10.1136/gut.2007.134502
44. Eun CS, Kim YS, Han DS, Choi JH, Lee AR, Park YK. Lactobacillus casei prevents impaired barrier function in intestinal epithelial cells. Apmis. 2011;119(1):49-56. doi: 10.1111/j.1600-0463.2010.02691.x
45. Gu S, Chen D, Zhang JN, Lv X, Wang K, Duan LP, et al. Bacterial community mapping of the mouse gastrointestinal tract. PLoS One. 2013;8(10):e74957. doi: 10.1371/journal.pone.0074957
46. Otte JM, Podolsky DK. Functional modulation of enterocytes bygram-positive and gram-negative microorganisms. Am J Physiol Gastrointest Liver Physiol. 2004;286(4):G613-G626. doi: 10.1152/ajpgi.00341.2003
47. Fuller R. Probiotics in human medicine. Gut. 1991;32(4):439-42. doi: 10.1136/gut.32.4.439
48. Sherman PM, Johnson-Henry KC, Yeung HP, Ngo PS, Goulet J, Tompkins TA. Probiotics reduce enterohemorrhagic Escherichia coli O157:H7- and enteropathogenic E. coli O127:H6-inducedchanges in polarized T84 epithelial cell monolayers by reducingbacterial adhesion and cytoskeletal rearrangements. Infect Immun. 2005;73(8):5183-8. doi: 10.1128/IAI.73.8.5183-5188.2005 
49. Watanabe T, Nishio H, Tanigawa T, Yamagami H, Okazaki H, Watanabe K, et al. Probiotic Lactobacillus case is train Shirotaprevents indomethacin-induced small intestinal injury: involvement of lactic acid. Am J Physiol Gastrointest Liver Physiol. 2009;297(3):G506-G513. doi: 10.1152/ajpgi.90553.2008
50. Sood A, Midha V, Makharia GK, Ahuja V, Singal D, Goswami P, et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2009;7(11):1202-9. doi: 10.1016/j.cgh.2009.07.016
51. McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Moyer KA, Melcher SA, et al. Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo. Am J Gastroenterol. 1995;90(3):439-48. 
52. Montalto M, Maggiano N, Ricci R, Curigliano V, Santoro L, DiNicuolo F, et al. Lactobacillus acidophilus protects tight junctions from aspirin damage in HT-29 cells. Digestion. 2004;69(4):225-8. doi: 10.1159/000079152
53. Kamil R, Geier MS, Butler RN, Howarth GS. Lactobacillus rhamnosus GG exacerbates intestinal ulceration in a model of indomethacin-induced enteropathy. Dig Dis Sci. 2007;52(2):1247-52. doi: 10.1007/s10620-006-9443-3
54. Zoetendal EG, Raes J, van den Bogert B, Arumugam M, Booijink CC, Troost FJ, et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J. 2012;6(7):1415-26. doi: 10.1038/ismej.2011.212
55. 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):11-7. 
56. Montalto M, Gallo A, Curigliano V, D’Onofrio F, Santoro L, Covino M, et al. Clinical trial: the effects of a probiotic mixtureon non-steroidal anti-inflammatory drug Enteropathy – a randomized, double-blind, cross-over, placebo-controlled study. Aliment Pharmacol Ther. 2010;32(2):209-14. doi: 10.1111/j.1365-2036.2010.04324.x
57. Cheng W, Lu J, Li B, et al. Effect of Functional Oligosaccharides and Ordinary Dietary Fiber on Intestinal Microbiota Diversity. Front Microbiol. 2017;8:1750. doi: 10.3389/fmicb.2017.01750 

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1. Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects ofnon-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24:121-32. doi: 10.1016/j.bpg.2009.11.005
2. Livzan MA, Lyalyukova EA, Kostenko MB. Non-steroid anti-inflammatory preparations: risk assessment and ways of the therapy safety enhancement. Lechashchiy Vrach. 2016;(5):78-82 (In Russ.)
3. Shostak NA, Ryabkova AA, Savelyev VS, Malyarova LP. Gastrointestinal hemorrhages as complications of gastropathies associated with intake of nonsteroid anti-inflammatory drugs. Therapeutic Archive. 2003;75(5):70-4 (In Russ.)
4. Montalto M, Gallo A, Gasbarrini A, Landolfi R. NSAID enteropathy: could probiotics prevent it? J Gastroenterol. 2013;48:689-97. doi: 10.1007/s00535-012-0648-2
5. Maiden L. Capsule endoscopic diagnosis of nonsteroidal anti-inflammatory drug-induced enteropathy. J Gastroenterol. 2009;19:64-71. doi: 10.1007/s00535-008-2248-8
6. Svistunov AA, Osadchuk MA, Kireeva NV, Hudarova AA, Achkasov EE. NSAID-induced enteropathy: the current state of the problem. Therapeutic Archive. 2018;90(8):95-100 (In Russ.) doi: 10.26442/terarkh201890895-100
7. Graham DY, Opekun AR, Willingham FF, Qureshi WA. Visiblesmall-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol. 2005;3:55-9. 
8. Zeino Z, Sisson G, Bjarnason I. Adverse effects of drugs on small intestine and colon. Best Pract Res Clin Gastroenterol. 2010;24:133-41. doi: 10.1016/j.bpg.2010.02.008
9. Gallo A, Passaro G, Gasbarrini A, Landolfi R, Montalto M. Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate. World J Gastroenterol. 2016;22(32):7186-202. doi: 10.3748/wjg.v22.i32.7186
10. Shimada S, Tanigawa T, Watanabe T, Nakata A, Sugimura N, Itani S, et al. Involvement of gliadin, a component of wheat gluten, in increased intestinal permeability leading to non-steroidal anti-inflammatory drug-induced small-intestinal damage. PLoS One. 2019;14(2):e0211436. doi: 10.1371/journal.pone.0211436. eCollection 2019.
11. Otani K, Tanigawa T, Watanabe T, Shimada S, Nadatani Y, Tanaka F, et al. Microbiota plays a key role in non-steroidal anti-inflammatory drug-induced small intestinal damage. Digestion. 2017;95:22-8. doi: 10.1159/000452356
12. Parfenov AI, Belostotsky NI, Khomeriki SG, Akhmadullina OV, Bykova SV, Sabelnikova EA, Dbar SR. Rebamipide increases the disaccharidases activity in patients with enteropathy with impaired membrane digestion. Pilot study. Therapeutic Archive. 2019;91(2):25-31 (In Russ.) doi: 10.26442/00403660.2019.02.000123
13. Robert A, Asano T. Resistance of germfree rats to indomethacin-induced intestinal lesions. Prostaglandins. 1977;14(2):333-41. 
14. Uejima M, Kinouchi T, Kataoka K, Hiraoka I, Ohnishi Y. Role of intestinal bacteria in ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug. Microbiol Immunol. 1996;40:553-60. 
15. Konaka A, Kato S, Tanaka A, Kunikata T, Korolkiewicz R, Takeuchi K. Roles of enterobacteria, nitric oxide and neutrophil in pathogenesis of indomethacin-induced small intestinal lesions in rats. Pharmacol Res. 1999;40(6):517-24. doi: 10.1006/phrs.1999.0550
16. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R: Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57(6):1470-81. doi: 10,2337/DB07-1403
17. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022-3. doi: 10.1038/4441022a
18. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482(7384):179-85. doi: 10.1038/nature10809
19. Donaldson RM Jr. Normal bacterial populations of the intestine and their relation to intestinal function. N Engl J Med. 1964;270:1050-6. doi: 10.1056/NEJM196405142702007
20. Muraki M, Fujiwara Y, Machida H, Okazaki H, Sogawa M, Yamagami H, et al. Role of small intestinal bacterial overgrowth in severe small intestinal damage in chronic non-steroidal anti-inflammatory drug users. Scand J Gastroenterol. 2014;49(3):267-73. doi: 10.3109/00365521.2014.880182
21. Wallace JL, Syer S, Denou E, de Palma G, Vong L, McKnight W, et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology. 2011;141(4):1314-22, e1-5. doi: 10.1053/j.gastro.2011.06.075
22. Watanabe T, Tanigawa T, Nadatani Y, Nagami Y, Sugimori S, Okazaki H, et al. Risk factors for severe nonsteroidal anti-inflammatory drug-induced small intestinal damage. Dig Liver Dis. 2013;45(5):390-5. doi: 10.1016/j.dld.2012.12.005
23. Endo H, Sakai E, Taniguchi L, Kessoku T, Komiya Y, Ezuka A, et al. Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users: data from a prospective multicenter capsule endoscopy registry. Gastrointest Endosc. 2014;80(5):826-34. doi: 10.1016/j.gie.2014.03.024
24. Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11(5):483-90. doi: 10.1016/j.cgh.2012.12.011
25. Higuchi K, Umegaki E, Watanabe T, Yoda Y, Morita E, Murano M, et al. Present status and strategy of NSAIDs-induced smallbowel injury. J Gastroenterol. 2009;44(9):879-88. doi: 10.1007/s00535-009-0102-2
26. Somasundaram S, Hayllar H, Rafi S, Wrigglesworth JM, Macpherson AJ, Bjarnason I. The biochemical basis of non-steroidalanti-inflammatory drug-induced damage to the gastrointestinaltract: a review and a hypothesis. Scand J Gastroenterol. 1995;30(4):289-99. doi: 10.3109/00365529509093280
27. Petruzzelli M, Vacca M, Moschetta A, CinziaSasso R, PalascianoG, van Erpecum KJ, et al. Intestinal mucosal damage causedby non-steroidal anti-inflammatory drugs: role of bile salts. ClinBiochem. 2007;40(8):503-10. doi: 10.1016/j.clinbiochem.2007.01.015
28. Watanabe T, Tanigawa T, Nadatani Y, Otani K, Machida H, Okazaki H, et al. Mitochondrial disorders in NSAIDs-induced small bowel injury. J Clin Biochem Nutr. 2011;48(2):117-21. 
29. Wallace JL. Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy. World J Gastroenterol. 2013;19(12):1861-76. doi: 10.3748/wjg.v19.i12.1861
30. Adebayo D, Bjarnason I. Is non-steroidal anti-inflammatory drug (NSAID) enteropathy clinically more important than NSAID gastropathy? Postgrad Med J. 2006;82(965):186-91. doi: 10.1136/pgmj.2005.039586
31. Livzan MA, Osipenko MF, Lyalyukova EA. Affection of digestion organs in patients taking non steroid antipyretic preparations: the factors of risk, strategy of conducting the patients. Lechashchiy Vrach. 2013;(7):27-34 (In Russ.) Available at: https://www.lvrach.ru/2013/07/15435749/
32. Vakhrushev YaM, Zagrebina EA. Enteropathy induced by nonsteroid anti-inflammatory drugs: pathogenesis, diagnosis, treatment. Terapeutic Archive. 2012;84(5):74-9 (In Russ.)
33. Fujimori S, Seo T, Gudis K, Ehara A, Kobayashi T, Mitsui K, et al. Prevention of nonsteroidal anti-inflammatory drug-induced small-intestinal injury by prostaglandin: a pilot randomized controlled trial evaluated by capsule endoscopy. Gastrointest Endosc. 2009;69(7):1339-46. doi: 10.1016/j.gie.2008.08.017
34. Niwa Y, Nakamura M, Ohmiya N, Maeda O, Ando T, Itoh A, et al. Efficacy of rebamipide for diclofenac-induced small-intestinal mucosal injuries in healthy subjects: a prospective, randomized, double-blinded, placebo-controlled, cross-over study. J Gastroenterol. 2008;43(2):270-6. doi: 10.1007/s00535-007-2155-4
35. Mizukami K, Murakami K, Abe T, Inoue K, Uchida M, Okimoto T, et al. Aspirin-induced small bowel injuries and the preventive effect of rebamipide. World J Gastroenterol. 2011;17(46):5117-22. doi: 10.3748/wjg.v17.i46.5117
36. Fujimori S, Takahashi Y, Gudis K, Seo T, Ehara A, Kobayashi T, et al. Rebamipide has the potential to reduce the intensity of NSAID-induced small intestinal injury: a double-blind, randomized, controlled trial evaluated by capsule endoscopy. J Gastroenterol. 2011;46(1):57-64. doi: 10.1007/s00535-010-0332-3
37. Lanas A, Scarpignato C. Microbial flora in NSAID-induced intestinal damage: a role for antibiotics? Digestion. 2006;73(1):136-50. doi: 10.1159/000089789
38. Davies GR, Wilkie ME, Rampton DS. Effects of metronidazole and misoprostol on indomethacin-induced changes in intestinal permeability. Dig Dis Sci. 1993;38(3):417-25. doi: 10.1007/bf01316493
39. Bjarnason I, Hayllar J, Smethurst P, Price A, Gumpel MJ. Metronidazole reduces intestinal inflammation and blood loss in nonsteroidal anti-inflammatory drug induced enteropathy. Gut. 1992;33(9):1204-8. doi: 10.1136/gut.33.9.1204
40. Reuter BK, Davles NM, Wallace JL. Nonsteroidal anti-inflammatory drug enteropathy in rats: role of permeability, bacteria, and enterohepatic circulation. Gastroenterology. 1997;112(1):109-17. doi: 10.1016/s0016-5085(97)70225-7
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Е.Н. Карева1,2

1 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБОУ ВО «Российский научно-исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия

________________________________________________

E.N. Kareva1,2

1 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russiа;
2 Pirogov Russian National Research Medical University, Moscow, Russia