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New Prospects of Cytoprotection in the Treatment and Prevention of Gastric and Intestinal Diseases (Resolution of an Expert Council and Literature Review)

https://doi.org/10.22416/1382-4376-2020-30-2-7-14

Abstract

Aim. To generalize up-to-date information on the possibilities of cytoprotection in the treatment and prevention of gastric and intestinal diseases, as well as to present the materials of an Expert Council meeting held on February 8, 2020 in Moscow under the support of the Alium company.

General provisions. The conducted Expert Council meeting was aimed at discussing the importance of improving the cytoprotective properties of the gastric and intestinal mucous membrane in the treatment of its lesions. It was shown that Rebamipide exhibits positive effects on various parts of the protective barrier of the gastrointestinal tract (GIT), primarily due to its stimulating action on the production of prostaglandins playing a key role in maintaining the cytoprotective properties of the gastrointestinal mucosa. The possibilities of applying Rebamipide for the treatment and prevention of erosive and ulcerative gastrointestinal lesions caused by non-steroidal anti-inflammatory (NSAIDs) and antithrombotic drugs were demonstrated. In the treatment of gastroesophageal reflux disease, Rebamipide is recommended for patients refractory to therapy with proton pump inhibitors (PPIs) and for those with non-acid reflux. The efficacy of Rebamipide in the treatment of Helicobacter pylori (H. pylori) infection, as well as functional dyspepsia and chronic gastritis, was confirmed.

Conclusions. Rebamipid is a highly effective drug positively affecting various cytoprotection links, thus being suitable for the treatment and prevention of erosive and ulcerative lesions of the gastrointestinal tract, as well as gastroenterological diseases of various etiologies.

Conflict of interest: The Expert Council meeting was supported by the Alium company.

About the Authors

A. I. Martynov
A.I. Yevdokimov Moscow State University of Medicine and Dentistry
Russian Federation

Anatoliy I. Martynov — Dr. Sci. (Med.), RAS Academician., Prof. of the Department of Hospital Therapy

127473, Moscow, Delegatskaya str., 20, build. 1.



A. A. Sheptulin
I.M. Sechenov First Moscow State Medical University
Russian Federation

Arkadiy A. Sheptulin — Dr. Sci. (Med.), Prof., Department of Internal Disease Propedeutics, Gastroenterology and Hepatology

19435, Moscow, Pogodinskaya str., 1, build. 1.



I. V. Mayev
A.I. Yevdokimov Moscow State University of Medicine and Dentistry
Russian Federation

Igor V. Maev — Dr. Sci. (Med.), RAS Academician. Prof., Head of the Department of Propedeutics of Internal Disease and Gastroenterology

127473, Moscow, Delegatskaya str., 20, build. 1.



A. N. Kazyulin
A.I. Yevdokimov Moscow State University of Medicine and Dentistry
Russian Federation

Alexander N. Kazyulin — Dr. Sci. (Med.), Prof. of the Department of Propedeutics of Internal Disease and Gastroenterology

127473, Moscow, Delegatskaya str., 20, build. 1.



A. Ye. Karateev
V.A. Nasonova Scientific Research Institute of Rheumatology
Russian Federation

Andrey Ye. Karateyev — Dr. Sci. (Med.), Prof.

115522, Moscow, Kashirskoe highway, 34A.



A. V. Melekhov
Pirogov Russian National Research Medical University
Russian Federation

Alexander V. Melekhov — Dr. Sci. (Med.), Assoc. Prof.

117997, Moscow, Ostrovityanova, 1.



L. K. Pal’gova
St. Petersburg State University
Russian Federation

Ludmila K. Palgova — Dr. Sci. (Med.), Prof., Scientific-Clinical and Educational center of Gastroenterology and Hepatology

199034, 7–9 Universitetskaya Emb., St Petersburg.



K. L. Raikhel’son
St. Petersburg State University
Russian Federation

Karina L. Raikhelson — Dr. Sci. (Med.), Prof., Scientific-Clinical and Educational center of Gastroenterology and Hepatology

199034, 7–9 Universitetskaya Emb., St Petersburg.



References

1. Kleine A., Kluge S., Peskar B.M. Stimulation of prostaglandine biosynthesis mediates gastroprotective effect of rebamipide in rats. Dig Dis Sci. 1993;38(8):1441–9.

2. Tanigawa T., Watanabe T., Ohkawa F., Nadatani Y., Otani K., Machida H., Okazaki H., Yamagami H., Watanabe K., Tominaga K., Fujiwara Y., Takeuchi K., Arakawa T. Rebamipide, a mucoprotective drug, inhibits NSAIDs-induced gastric mucosal injury: possible involvement of the downregulation of 15-hydroxyprostaglandin dehydrogenase. J Clin Biochem Nutr. 2011;48(2):149– 53. https://doi.org/10.3164/jcbn.10-75

3. Iijima K., Ichikawa T., Okada S. Rebamipide, a cytoprotective drug, increases gastric mucus secretion in human: evaluations with endoscopic gastrin test. Dig Dis Sci. 2009;54(7):1500–7.

4. Ishihara K., Komuro Y., Nishiyama N., Yamasaki K., Hotta K. et al. Effect of rebamipide on mucus secretion by endogenous prostaglandin-independent mechanism in rat gastric mucosa. Arzneimittelforschung. 1992;42(12): 1462–6. https://doi.org/10.1067/mlc.2000.107303

5. Tarnawski A., Arakawa T., Kobayashi K. Rebamipide treatment activates epidermal growth factor and its receptor expression in normal and ulcerated gastric mucosa in rats: one mechanism for its ulcer healing action? Dig Dis Sci. 1998;43(9):90S–98S.

6. Kim H.K., Kim J.I., Kim J.K., Han J.Y., Park S.H., Choi K.Y., Chung I.S. Рreventive effects of rebamipide on NSAID-induced gastric mucosal injury and reduction of gastric mucosal blood flow in healthy volunteers. Dig Dis Sci. 2007;52(8):1776–82. https://doi.org/10.1007/s10620-006-9367-y

7. Naito Y., Yoshikawa T., Tanigawa T., Sakurai K., Yamasaki K., Uchida M., Kondo M. Hydroxil radical scavenging by rebamipide and related compounds: electron paramagnetic resonance study. Free Radic Biol Med. 1995;18(1):117–23. https://doi.org/10.1016/0891-5849(94)00110-6

8. Sakurai K., Osaka T., Yamasaki K. Rebamipide reduces recurrence of experimental gastric ulcers: role of free radicals and neutrophils. Dig Dis Sci. 2005;50(suppl.1): S90–6.

9. Diao L., Mei Q., Xu J.M., Liu X.C., Hu J., Jin J., Yao O., Chen M.L. Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice. World J Gastrenterol. 2012;18(10):1059–66. https://doi.org/10.3748/wjg.v18.i10.1059

10. Yoshida N., Kamada K., Tomatsuri N., Tomatsuri N., Suzuki T., Takagi T., Ichikawa H., Yoshikawa T. Management of recurrence of symptoms of gastroesophageal reflux disease: synergestic effect of rebamipide with 15 mg lanxoprazole. Dig Dis Sci. 2010;55(12):3393–8. https://doi.org/10.1007/s10620-010-1166-9

11. Hong S.J., Park S.H., Moon J.S., Shin W.G., Kim J.G., Lee Y.C., Lee D.H., Jang J.Y., Kim J.J., Lee H.L., Lee S.W., Hwangbo Y., Xu J., Wang B., Xue Z., Liu F., Yuan Y., Leelakusolvong S., Dy F. The benefits of combination therapy with esomeprazole and rebamipide in symptom improvement in reflux esophagitis: An international multicenter study. Gut Liver. 2016;10(6):910–916. https://doi.org/10.5009/gnl15537

12. Nishizawa T., Nishizawa Y., Yahagi N., Kanai T., Takahashi M., Suzuki H. Effect of supplementation with rebamipide for Helicobacter pylori eradication therapy: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2014;29(suppl.4):20–4. https://doi.org/10.1111/jgh.12769

13. Andreev D.N., Maev I.V., Dicheva D.T. Efficiency of the inclusion of rebamipide in the eradication therapy for Helicobacter pylori infection. J Clin Med. 2019;8(9). pii:E1498.

14. Jaafar M.H., Safi S.Z., Tan M.P., Rampal S., Mahadeva S. Efficacy of rebamipide in organic and functional dyspepsia: a systematic review and meta-analysis. Dig Dis Sci. 2018;63(5):1250–60. https://doi.org/10.1007/s10620-017-4871-9

15. Terano A., Arakawa T., Sugiyama T., Suzuki H., Joh T., Yoshikawa T., Higuchi K., Haruma K., Murakami K., Kobayashi K. Rebamipide, a gastro-protective and antiinflammatory drug, promotes gastric ulcer healing following eradication therapy for Helicobacter pylori in a Japanese population: a randomized, double-blind, placebo-controlled trial. J Gastroenterol. 2007;42(8):690–3. https://doi.org/10.1007/s00535-007-2076-2

16. Tsukamoto H., Mizoshita T., Katano T., Hayashi N., Ozeki K., Ebi M., Shimura T., Mori Y., Tanida S., Kataoka H., Tsukamoto T., Tatematsu M., Joh T. Preventive effect of rebamipide on N-methyl-N’-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats. Exp Toxicol Pathol. 2015;67(3):271–7. https://doi.org/10.1016/j.etp.2015.01.003

17. Tanigawa T., Pai R., Arakawa T., Tarnawski A.S Rebamipide inhibits gastric cancer cell growth. Dig Dis Sci. 2007;52(8):240–7.

18. Kang D.W., Min G., Park D.Y., Hong K.W., Min D.S. Rebamipide-induced down-regulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells. Exp Mol Med. 2010;42(8):555–64. https://doi.org/10.3858/emm.2010.42.8.056

19. Mayev I.V., Kazyulin A.N. New opportunities for the prevention of gastric cancer. Terapevticheskiy arkhiv. 2017;89(4):101–9 (In Russ.)

20. Yan B., Lu Z., Ge Z., Liu S., Guo X., Tian D., Yang Y., Li X., Gong W., Liu Z., Liu M., Zhou B., Zhao K., Pan F., Yang J., Yang Y. A multicenter, randomized, controlled trial of rebamipide plus lansoprazole for the treatment of postendoscopic submucosal dissection ulcers. Clin Transl Gastroenterol. 2019;10(1):e00008. https://doi.org/10.14309/ctg.0000000000000008

21. Xiong J., Lai S., Zhang P., Li Q., Wei Y., Yang Y., Wang T., Liu L., Ma X., Chen D. Rebamipide plus proton pump inhibitor versus proton pump inhibitor alone in the treatment of endoscopic submucosal dissection-induced gastric ulcer: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2014;93(12):e64. https://doi.org/10.1097/MD.0000000000000064

22. Wang J., Guo X., Ye C., Yu S., Zhang J., Song J., Cao Z., Wang J., Liu M., Dong W. Efficacy and safety of proton pump inhibitors (PPIs) plus rebamipide for endoscopic submucosal dissection-induced ulcers: a meta-analysis. Intern Med. 2014;53(12):1243–8. https://doi.org/10.2169/internalmedicine.53.2160

23. Nishizawa T., Suzuki H., Kanai T., Yahagi N. Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective agents for endoscopic submucosal dissection-induced ulcer: a systematic review and meta-analysis. J Clin Biochem Nutr. 2015;56(2):85–90.

24. Gao F., Chen X., Zhang J. Prevalence of gastric and small-intestinal mucosal injury in elderly patients taking enteric-coated aspirin by magnetically controlled capsule endoscopy. Gastroenterol Res Pract. 2019:1582590. https://doi.org/10.1155/2019/1582590

25. Tziatzios G., Gkolfakis P., Papanikolaou I.S., Triantafyllou K. Antithrombotic treatment is associated with small-bowel video capsule endoscopy positive findings in obscure gastrointestinal bleeding: A systematic review and meta-analysis. Dig Dis Sci. 2019;64(1):15–24.

26. Cheung K.S., Leung W.K. Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management. World J Gastroenterol. 2017;23(11): 1954–63.

27. Fawzy A.M., Yang W.Y., Lip G.Y. Safety of direct oral anticoagulants in real-world clinical practice: translating the trials to everyday clinical management. Expert Opin Drug Saf. 2019;18(3):187–209.

28. Watanabe T., Takeuchi T., Handa O., Sakata Y., Tanigawa T., Shiba M., Naito Y., Higuchi K., Fujimoto K., Yoshikawa T., Arakawa T. A multicenter, randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage. PLoS One. 2015;10(4): e0122330.

29. Hasegawa M., Horiki N., Tanaka K., Wakabayashi H., Tano S., Katsurahara M., Uchida A., Takei Y., Sudo A. The efficacy of rebamipide add-on therapy in arthritic patients with COX-2 selective inhibitor-related gastrointestinal events: a prospective, randomized, open-label blinded-endpoint pilot study by the GLORIA study group. Mod Reumatol. 2013;23(6):1172–8. https://doi.org/10.1007/s10165-012-0819-2

30. Kim T.J., Kim E.R., Hong S.N., Kim Y.H., Lee Y.C., Kim H.S., Kim K., Chang D.K. Effectiveness of acid suppressants and other mucoprotective agents in the reducing the risk of occult gastrointestinal bleeding in non-steroidal anti-inflammatory drug users. Sci Rep. 2019;9(1):11696. https://doi.org/10.1038/s41598-019-48173-6

31. Zhang S., Qing Q., Bai Y., Mao H., Zhu W., Chen Q., Zhang Y., Chen Y. Rebamipide helps defend against non-steroidal anti-inflammatory drugs induced gastroenteropathy: a systemic review and meta-analysis. Dig Dis Sci. 2013;58(7):1991–2000. https://doi.org/10.1007/s10620-013-2606-0

32. Kim J.H., Park S.H., Cho C.S., Lee S.T., Yoo W.H., Kim S.K., Kang Y.M., Rew J.S., Park Y.W., Lee S.K., Lee Y.C., Park W., Lee D.H. Preventive efficacy and safety of rebamipide in nonsteroidal anti-inflammatory drug-induced mucosal toxicity. Gut Liver. 2014;8(4): 371–9. https://doi.org/10.5009/gnl.2014.8.4.371

33. Niwa Y., Nakamura M., Ohmiya N., Maeda O., Ando T., Itoh A., Hirooka Y., Goto H. Efficacy of rebamipide for dichlofenac-induced small-intestinal mucosal injures in healthy subjects: a prospective, randomized, double-blinded, placebo-controlled, cross-over study. J Gastroenterol. 2008;43(4):270–6. https://doi.org/10.1007/s00535-007-2155-4

34. Nasonov Ye. L., Ivashkin V.T., Yakhno N.N., Martynov A.I., Arutyunov G.P., Karateev A.E., Alexeyeva L.I., Chichasova N.V., Evseyev M.A., Kukushkin M.L., Lila A.M., Rebrov A.P., Novikova D.S., Kopenkin S.S., Abuzarova G.R., Scorobogatykh K.V., Lapina T.L., Popkova T.V. National clinical guidelines (summary) of Association of rheumatologists of Russia, Russian gastroenterological association, Russian Association for the study of pain “Rational treatment by non-steroidal anti-inflammatory drugs”: the draft. (Data of expert board meeting, Moscow, 01.04.2017). Rus J Gastroenterol Hepatol Coloproctol. 2017;27(5):69-75.

35. Ratelle M., Perreault S., Villeneuve J.P., Tremblay L. Association between proton pump inhibitor use and spontaneous bacterial peritonitis in cirrhotic patients with ascites. Can J Gastroenterol Hepatol. 2014;28(6):330–4.

36. Dultz G., Piiper A., Zeuzem S., Kronenberger B., Waidmann O. Proton pump inhibitor treatment is associated with the severity of liver disease and increased mortality in patients with cirrhosis. Aliment Pharmacol Ther. 2015;41(5):459–66.

37. Kinjo N., Kawanaka H., Akahoshi T., Yamaguchi S., Yoshida D., Anegawa G., Konishi K., Tomikawa M., Tanoue K., Tarnawski A., Hashizume M., Maehara Y. Significance of ERK nitration in portal hypertensive gastropathy and its therapeutic implications. Am J Physiol Gastrointest Liver Physiol. 2008;295:G1016-G1024. https://doi.org/10.1152/ajpgi.90329.2008

38. Ali S. I. Use of rebamipide and /or propranolol for treatment of portal hypertensive gastropathy in patients with liver cirrhosis [dissertation]? Beni-Suef, Beni-Suef University; 2017.

39. Karim A.S.S. Effect of rebamipide on portal hypertensive gastropathy and proliferating cell nuclear antigen in patients with liver cirrhosis. [dissertation]. Alexandria: University of Alexandria; 2012.

40. Soliman G. M. Mostafa, S. Comparative study between the efficacy of rebamipide, sucralfate and pantoprazole in treatment of post banding variceal ulcers. Al-Azhar Assiut Med. 2015;13(1)(Suppl 2):28–35.

41. Zakaria S., El-Sisi A. Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2. J Immunotoxicol. 2016;13(4):453–62.

42. Hong K.W., Kim K.E., Rhim B.Y., Lee W.S., Kim C.D. Effect of rebamipide on liver damage and increased tumor necrosis factor in a rat model of endotoxin shock. Dig Dis Sci. 1998;43(9)(Suppl):154S–159S.

43. Gendy A.M., Abdallah D.M., El-Abhar H.S. The potential curative effect of rebamipide in hepatic ischemia/reperfusion injury. Naunyn Schmiedebergs Arch Pharmacol. 2017;390(7):691–700.


Review

For citations:


Martynov A.I., Sheptulin A.A., Mayev I.V., Kazyulin A.N., Karateev A.Ye., Melekhov A.V., Pal’gova L.K., Raikhel’son K.L. New Prospects of Cytoprotection in the Treatment and Prevention of Gastric and Intestinal Diseases (Resolution of an Expert Council and Literature Review). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(2):7-14. (In Russ.) https://doi.org/10.22416/1382-4376-2020-30-2-7-14

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