Effect of Long-term Administration of Rebamipide on <em>H. pylori</em> Infection in Mice

Original

대한Helicobacter 연구학회지 2002;2(1):36-49.
Published online June 21, 2002.

Effect of Long-term Administration of Rebamipide on H. pylori Infection in Mice

Helicobacter pylori 감염 마우스에서 Rebamipide 장기 투여 효과

정재연·이은희·김도현·황재철·이기명·유병무·김영배^†·주희재^†·박해심*·김용석*·김진홍·조성원·함기백

아주대학교 의과대학 소화기내과, *간 및 소화기질환 유전체 연구센터, ^†아주대학교 의과대학 H. pylori 연구 그룹

Abstract

Background/Aim: It has been suggested that chronic, persistent, uncontrolled inflammations in the stomach could provide the basic step for the carcinogenesis. One of potential clinical applications of rebamipide is the inhibition of the immunoinflammatory response in gastric mucosa infected with Helicobacter pylori. To know the implication of long-term rebamipide treatment in H. pylori infection, we studied the underlying moleculo-pathological changes of gastric lesions in mice infected with H. pylori(SS1 strain), especially after long-term administration of rebamipide. 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, IL-10, mRNA transcripts of various mouse cytokines and chemokines, and NF-kB binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group(HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets(HPR). Results: Serum levels of IL-1β, IFN-γ, and TNF-α, gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-kB binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes like caspase-8, FasL, Fas, TRAIL and various cytokines genes like IFN-γ, RANTES, TNF-α, TNFR p75, IL-1β in rebamipide administered group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group. However, long- term administration of rebamipide showed the advantage of decreasing precancerous lesion like chronic atrophic gastritis and showed the molecular evidence of attenuating proliferation. Conclusion: Long-term administration of rebamipide should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages like lessening gastric inflammation and possible chemopreventive effect. (Korean J Helicobacter Res Prac 2002;1:36-49)

Key Words: Antiinflammation, Chemoprevention, Cytokines, Helicobacter pylori, Rebamipide