Skip to main content
SpringerLink
Log in

Preventive Effects of Rebamipide on NSAID-Induced Gastric Mucosal Injury and Reduction of Gastric Mucosal Blood Flow in Healthy Volunteers

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The precise mechanisms of acute damage and the role of gastric mucosal blood flow in gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) remain uncertain. The aim of this study was to evaluate the preventive effect of rebamipide on gastric mucosal injury and reduction of gastric mucosal blood flow (GMBF) after ibuprofen administration. Twenty healthy volunteers were randomized two groups. The rebamipide group took ibuprofen, 1800 mg/day, and rebamipide, 100 mg t.i.d., for 7 days. The placebo group took ibuprofen, 1800 mg/day. The numbers of gastric ulcer subjects were three in the placebo group and zero in the rebamipide group. The mean modified Lanza score after ibuprofen administration was significantly higher in the placebo group than the rebamipide group (2.9±1.7 vs. 1.3±1.0, respectively; P=0.032). The GMBF of the placebo group was significantly decreased at antrum from baseline, from 2.8±0.5 to 2.0±0.5 tissue perfusion units (P=0.005). There was no difference in GMBF change in the rebamipide group. Gastric mucosal injury was correlated with GMBF reduction in antrum (r=−0.677, P=0.001). In conclusion, it is suggested that the decrease in GMBF may have been associated with NSAID-induced gastric mucosal injury, and rebamipide may have prevented NSIAD-induced gastric mucosal injury by maintaining GMBF in healthy subjects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Anonymous (1992) Anti-arthritis medication usage: United States 199l. Stat Bull Metrop Insur Co 73:25–34

    Google Scholar 

  2. Henry D, Lim LL, Garcia Rodriguez LA et al (1996) Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. BMJ 312:1563–1566

    PubMed  CAS  Google Scholar 

  3. Gabriel SE, Jaakkimainen L, Bombardier C (1991) Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis. Ann Intern Med 115:787–796

    CAS  Google Scholar 

  4. Bollini P, Garcia Rodriguez LA, Perez Gutthann S, Walker AM (1992) The impact of research quality and study design on epidemiologic estimates of the effect of nonsteroidal anti-inflammatory drugs on upper gastrointestinal tract disease. Arch Intern Med 152:1289–1295

    Article  PubMed  CAS  Google Scholar 

  5. Ashley SW, Sonnenschein LA, Cheung LY (1985) Focal gastric mucosal blood flow at the site of aspirin-induced ulceration. Am J Surg 149:53–59

    Article  PubMed  CAS  Google Scholar 

  6. Kitahora T, Guth PH (1987) Effect of aspirin plus hydrochloric acid on the gastric mucosal microcirculation. Gastroenterology 93:810–817

    PubMed  CAS  Google Scholar 

  7. Gana TJ, Huhlewych R, Koo J (1987) Focal gastric mucosal blood flow in aspirin-induced ulceration. Ann Surg 205:399–403

    Article  PubMed  CAS  Google Scholar 

  8. Del Soldato P, Foschi D, Benoni G, Scarpignato C (1985) Oxygen free radicals interact with indomethacin to cause gastrointestinal injury. Agents Actions 17:484–488

    Article  CAS  Google Scholar 

  9. Vaananen PM, Meddings JB, Wallace JL (1991) Role of oxygen-derived free radicals in indomethacin-induced gastric injury. Am J Physiol 261:G470–G475

    PubMed  CAS  Google Scholar 

  10. Murakami K, Okajima K, Uchiba M et al (1997) Rebamipide attenuates indomethacin-induced gastric mucosal lesion formation by inhibiting activation of leukocytes in rats. Dig Dis Sci 42:319–325

    Article  PubMed  CAS  Google Scholar 

  11. Kleine A, Kluge S, Peskar BM (1993) Stimulation of prostaglandin biosynthesis mediates gastroprotective effect of rebamipide in rats. Dig Dis Sci 38:1441–1449

    Article  PubMed  CAS  Google Scholar 

  12. Oka S, Ogino K, Hobara T et al (1991) Effects of various mucosal protective drugs on diethyldithiocarbamate-induced antral ulcer in rats. Eur J Pharmacol 197:99–102

    Article  PubMed  CAS  Google Scholar 

  13. Lanza FL, Royer GL Jr, Nelson RS et al (1981) A comparative endoscopic evaluation of the damaging effects of nonsteroidal anti-inflammatory agents on the gastric and duodenal mucosa. Am J Gastroenterol 75:17–21

    PubMed  CAS  Google Scholar 

  14. Lanza FL (1984) Endoscopic studies of gastric and duodenal injury after the use of ibuprofen, aspirin, and other nonsteroidal anti-inflammatory agents. Am J Med 77:19–24

    PubMed  CAS  Google Scholar 

  15. Naito Y, Yoshikawa T, Iinuma S, Yagi N et al (1998) Rebamipide protects against indomethacin-induced gastric mucosal injury in healthy volunteers in a double-blind, placebo-controlled study. Dig Dis Sci 43 (Suppl 9):83S–89S

    PubMed  CAS  Google Scholar 

  16. Murakami K, Okajima K, Harada N, Isobe H, Okabe H (1998) Rebamipide prevents indomethacin-induced gastric mucosal lesion formation by inhibiting activation of neutrophils in rats. Dig Dis Sci 43(Suppl 9):139S–142S

    PubMed  CAS  Google Scholar 

  17. Konturek JW, Dembinski A, Stoll R, Domschke W, Konturek SJ (1994) Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth and neutrophil activation. Gut 35:1197–1204

    PubMed  CAS  Google Scholar 

  18. Konturek SJ, Konturek JW (1994) Gastric adaptation: basic and clinical aspects. Digestion 55:131–138

    Article  PubMed  CAS  Google Scholar 

  19. Lipscomb GR, Wallis N, Armstrong G, Goodman MJ, Rees WD (1995) Gastric mucosal adaptation to etodolac and naproxen. Aliment Pharmacol Ther 9:379–385

    Article  PubMed  CAS  Google Scholar 

  20. Lipscomb GR, Rees WDW (1996) Gastric mucosal injury and adaptation to oral and rectal administration of naproxen. Aliment Pharmacol Ther 10:133–138

    Article  PubMed  CAS  Google Scholar 

  21. Wallace JL, Granger DN (1992) Pathogenesis of NSAID-gastropathy: are neutrophils the culprits? Trends Pharmacol Sci 13:129–131

    Article  PubMed  CAS  Google Scholar 

  22. Wallace JL (1997) Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroeterology 112:1000–1016

    Article  CAS  Google Scholar 

  23. Guslandi M, Foppa L, Fanti L, Sorghi M (1999) Nonsteroidal anti-Inflammatory drugs and gastric mucosal blood flow. J Clin Gastroenterol 28:258–260

    Article  PubMed  CAS  Google Scholar 

  24. Shorrock CJ, Rees WD (1992) Mucosal adaptation to indomethacin induced gastric damage in man: studies on morphology, blood flow and PGE2 metabolism. Gut 33:164–169

    PubMed  CAS  Google Scholar 

  25. Chan FK, Sung JJ (2000) How does Helicobacter pylori infection interact with non-steroidal anti-inflammatory drugs? Baillieres Clin Gastroenterol 14:161–172

    Article  Google Scholar 

  26. Wu CY, Poon SK, Chen GH, Chang CS, Yeh HZ (1999) Interaction between Helicobacter pylori and non-steroidal anti-inflammatory drugs in peptic ulcer bleeding. Scand J Gastroenterol 34:234–237

    Article  PubMed  CAS  Google Scholar 

  27. Okan A, Tankurt E, Aslan BU, Akpinar H, Simsek I, Gonen O (2003) Relationship between non-steroidal anti-inflammatory drug use and Helicobacter pylori infection in bleeding or uncomplicated peptic ulcers: A case-control study. J Gastroenterol Hepatol 18:18–25

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This research was supported by a Fujinon Grant from the Korean Society of Gastrointestinal Endoscopy.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, and Uijeongbu St. Mary’s Hospital, Uijeongbu City, Korea

    Hyung-Keun Kim

  2. Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea and St. Mary’s Hospital, 62 Yeouido-dong, Yeongdeungpo-gu, Seoul, 150-713, Korea

    Jin-Il Kim, Jae-Kwang Kim, Joon-Yeol Han & Soo-Heon Park

  3. Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea and Our Lady of Mercy Hospital, Incheon, Korea

    Kyu-Yong Choi

  4. Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea and Kangnam St. Mary’s Hospital, Seoul, Korea

    In-Sik Chung

Authors
  1. Hyung-Keun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin-Il Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jae-Kwang Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joon-Yeol Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Soo-Heon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kyu-Yong Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. In-Sik Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Soo-Heon Park.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, HK., Kim, JI., Kim, JK. et al. Preventive Effects of Rebamipide on NSAID-Induced Gastric Mucosal Injury and Reduction of Gastric Mucosal Blood Flow in Healthy Volunteers. Dig Dis Sci 52, 1776–1782 (2007). https://doi.org/10.1007/s10620-006-9367-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9367-y

Keywords

Search

Navigation