Effect of long-term administration of rebamipide on Helicobacter pylori infection in mice

Ki Baik Hahm, D. H. Kim, K. M. Lee, J. S. Lee, Y. J. Surh, Y. B. Kim, B. M. Yoo, J. H. Kim, H. J. Joo, Y. K. Cho, KiTaek Nam, S. W. Cho

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: It has been suggested that chronic, persistent, uncontrolled inflammations in the stomach could provide the basic step for the beginning of carcinogenesis. One of the potential clinical applications of rebamipide is the inhibition of the immuno-inflammatory response in gastric mucosa imposed by Helicobacter pylori. Aim: To determine the implications of long-term rebamipide treatment in H. pylori infection, we studied the underlying moleculo-pathological changes in gastric lesions in mice infected with H. pylori (SS1 strain), following this treatment. Methods: C57BL/6 mice were sacrificed 24 and 50 weeks after H. pylori infection, respectively. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels of IL-1β, TNF-α IFN-γ and IL-10, mRNA transcripts of various mouse cytokines and chemokines, and NF-κB binding activities, and finally the presence of gastric adenocarcinoma were compared between an H. pylori infected group (HP), and an H. pylori infected group administered with long-term rebamipide-containing pellet diets (HPR). Results: Serum levels of IL-1β, IFN-γ and TNF-α, the gastric mucosal expression of ICAM-1, HCAM and MMP, and transcriptional regulation of NF-κB-DNA binding were all significantly decreased in the HPR group compared with the HP group. An RNase protection assay showed, in the rebamipide administered group, significantly decreased mRNA levels of apoptosis-related genes such as caspase-8, FasL, Fas, TRAIL and various cytokines genes such as IFN-γ, RANTES, TNF-α, TNFR p75, IL-1β. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not different in either group. However. long-term administration of rebamipide showed the advantage of decreasing precancerous lesions like chronic atrophic gastritis and showed molecular evidence of attenuation of proliferation. Conclusion: The long-term administration of rebamipide should be considered in the treatment of H. pylori since it demonstrated molecular and biological advantages like a lessening of gastric inflammation and a possible chemopreventive effect.

Original languageEnglish
Pages (from-to)24-38
Number of pages15
JournalAlimentary Pharmacology and Therapeutics, Supplement
Volume18
Issue number1
Publication statusPublished - 2003 Jul 1

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Helicobacter Infections
Helicobacter pylori
Stomach
Interleukin-1
Atrophic Gastritis
Inflammation
Receptors, Tumor Necrosis Factor, Type II
B-Form DNA
Cytokines
rebamipide
Chemokine CCL5
Messenger RNA
Caspase 8
Metaplasia
Intercellular Adhesion Molecule-1
Ribonucleases
Gastric Mucosa
Serum
Matrix Metalloproteinases
Inbred C57BL Mouse

All Science Journal Classification (ASJC) codes

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

Cite this

Hahm, K. B., Kim, D. H., Lee, K. M., Lee, J. S., Surh, Y. J., Kim, Y. B., ... Cho, S. W. (2003). Effect of long-term administration of rebamipide on Helicobacter pylori infection in mice. Alimentary Pharmacology and Therapeutics, Supplement, 18(1), 24-38.
Hahm, Ki Baik ; Kim, D. H. ; Lee, K. M. ; Lee, J. S. ; Surh, Y. J. ; Kim, Y. B. ; Yoo, B. M. ; Kim, J. H. ; Joo, H. J. ; Cho, Y. K. ; Nam, KiTaek ; Cho, S. W. / Effect of long-term administration of rebamipide on Helicobacter pylori infection in mice. In: Alimentary Pharmacology and Therapeutics, Supplement. 2003 ; Vol. 18, No. 1. pp. 24-38.
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abstract = "Background: It has been suggested that chronic, persistent, uncontrolled inflammations in the stomach could provide the basic step for the beginning of carcinogenesis. One of the potential clinical applications of rebamipide is the inhibition of the immuno-inflammatory response in gastric mucosa imposed by Helicobacter pylori. Aim: To determine the implications of long-term rebamipide treatment in H. pylori infection, we studied the underlying moleculo-pathological changes in gastric lesions in mice infected with H. pylori (SS1 strain), following this treatment. Methods: C57BL/6 mice were sacrificed 24 and 50 weeks after H. pylori infection, respectively. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels of IL-1β, TNF-α IFN-γ and IL-10, mRNA transcripts of various mouse cytokines and chemokines, and NF-κB binding activities, and finally the presence of gastric adenocarcinoma were compared between an H. pylori infected group (HP), and an H. pylori infected group administered with long-term rebamipide-containing pellet diets (HPR). Results: Serum levels of IL-1β, IFN-γ and TNF-α, the gastric mucosal expression of ICAM-1, HCAM and MMP, and transcriptional regulation of NF-κB-DNA binding were all significantly decreased in the HPR group compared with the HP group. An RNase protection assay showed, in the rebamipide administered group, significantly decreased mRNA levels of apoptosis-related genes such as caspase-8, FasL, Fas, TRAIL and various cytokines genes such as IFN-γ, RANTES, TNF-α, TNFR p75, IL-1β. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not different in either group. However. long-term administration of rebamipide showed the advantage of decreasing precancerous lesions like chronic atrophic gastritis and showed molecular evidence of attenuation of proliferation. Conclusion: The long-term administration of rebamipide should be considered in the treatment of H. pylori since it demonstrated molecular and biological advantages like a lessening of gastric inflammation and a possible chemopreventive effect.",
author = "Hahm, {Ki Baik} and Kim, {D. H.} and Lee, {K. M.} and Lee, {J. S.} and Surh, {Y. J.} and Kim, {Y. B.} and Yoo, {B. M.} and Kim, {J. H.} and Joo, {H. J.} and Cho, {Y. K.} and KiTaek Nam and Cho, {S. W.}",
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Hahm, KB, Kim, DH, Lee, KM, Lee, JS, Surh, YJ, Kim, YB, Yoo, BM, Kim, JH, Joo, HJ, Cho, YK, Nam, K & Cho, SW 2003, 'Effect of long-term administration of rebamipide on Helicobacter pylori infection in mice', Alimentary Pharmacology and Therapeutics, Supplement, vol. 18, no. 1, pp. 24-38.

Effect of long-term administration of rebamipide on Helicobacter pylori infection in mice. / Hahm, Ki Baik; Kim, D. H.; Lee, K. M.; Lee, J. S.; Surh, Y. J.; Kim, Y. B.; Yoo, B. M.; Kim, J. H.; Joo, H. J.; Cho, Y. K.; Nam, KiTaek; Cho, S. W.

In: Alimentary Pharmacology and Therapeutics, Supplement, Vol. 18, No. 1, 01.07.2003, p. 24-38.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of long-term administration of rebamipide on Helicobacter pylori infection in mice

AU - Hahm, Ki Baik

AU - Kim, D. H.

AU - Lee, K. M.

AU - Lee, J. S.

AU - Surh, Y. J.

AU - Kim, Y. B.

AU - Yoo, B. M.

AU - Kim, J. H.

AU - Joo, H. J.

AU - Cho, Y. K.

AU - Nam, KiTaek

AU - Cho, S. W.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - Background: It has been suggested that chronic, persistent, uncontrolled inflammations in the stomach could provide the basic step for the beginning of carcinogenesis. One of the potential clinical applications of rebamipide is the inhibition of the immuno-inflammatory response in gastric mucosa imposed by Helicobacter pylori. Aim: To determine the implications of long-term rebamipide treatment in H. pylori infection, we studied the underlying moleculo-pathological changes in gastric lesions in mice infected with H. pylori (SS1 strain), following this treatment. Methods: C57BL/6 mice were sacrificed 24 and 50 weeks after H. pylori infection, respectively. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels of IL-1β, TNF-α IFN-γ and IL-10, mRNA transcripts of various mouse cytokines and chemokines, and NF-κB binding activities, and finally the presence of gastric adenocarcinoma were compared between an H. pylori infected group (HP), and an H. pylori infected group administered with long-term rebamipide-containing pellet diets (HPR). Results: Serum levels of IL-1β, IFN-γ and TNF-α, the gastric mucosal expression of ICAM-1, HCAM and MMP, and transcriptional regulation of NF-κB-DNA binding were all significantly decreased in the HPR group compared with the HP group. An RNase protection assay showed, in the rebamipide administered group, significantly decreased mRNA levels of apoptosis-related genes such as caspase-8, FasL, Fas, TRAIL and various cytokines genes such as IFN-γ, RANTES, TNF-α, TNFR p75, IL-1β. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not different in either group. However. long-term administration of rebamipide showed the advantage of decreasing precancerous lesions like chronic atrophic gastritis and showed molecular evidence of attenuation of proliferation. Conclusion: The long-term administration of rebamipide should be considered in the treatment of H. pylori since it demonstrated molecular and biological advantages like a lessening of gastric inflammation and a possible chemopreventive effect.

AB - Background: It has been suggested that chronic, persistent, uncontrolled inflammations in the stomach could provide the basic step for the beginning of carcinogenesis. One of the potential clinical applications of rebamipide is the inhibition of the immuno-inflammatory response in gastric mucosa imposed by Helicobacter pylori. Aim: To determine the implications of long-term rebamipide treatment in H. pylori infection, we studied the underlying moleculo-pathological changes in gastric lesions in mice infected with H. pylori (SS1 strain), following this treatment. Methods: C57BL/6 mice were sacrificed 24 and 50 weeks after H. pylori infection, respectively. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels of IL-1β, TNF-α IFN-γ and IL-10, mRNA transcripts of various mouse cytokines and chemokines, and NF-κB binding activities, and finally the presence of gastric adenocarcinoma were compared between an H. pylori infected group (HP), and an H. pylori infected group administered with long-term rebamipide-containing pellet diets (HPR). Results: Serum levels of IL-1β, IFN-γ and TNF-α, the gastric mucosal expression of ICAM-1, HCAM and MMP, and transcriptional regulation of NF-κB-DNA binding were all significantly decreased in the HPR group compared with the HP group. An RNase protection assay showed, in the rebamipide administered group, significantly decreased mRNA levels of apoptosis-related genes such as caspase-8, FasL, Fas, TRAIL and various cytokines genes such as IFN-γ, RANTES, TNF-α, TNFR p75, IL-1β. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not different in either group. However. long-term administration of rebamipide showed the advantage of decreasing precancerous lesions like chronic atrophic gastritis and showed molecular evidence of attenuation of proliferation. Conclusion: The long-term administration of rebamipide should be considered in the treatment of H. pylori since it demonstrated molecular and biological advantages like a lessening of gastric inflammation and a possible chemopreventive effect.

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