Effects of rebamipide, a gastro‐protective drug on the <i>Helicobacter pylori</i> status and inflammation in the gastric mucosa of patients with gastric ulcer: a randomized double‐blind placebo‐controlled multicentre trial

Fujioka, Toshio; Shimoyama, Takashi; Yoshikawa, Toshikazu; Itoh, Makoto; Asaka, Masahiro; Ishii, Hiromasa; Kuwayama, Hajime; Sato, Ryugo; Kawai, Shioko; Takemoto, Tadayoshi; Kobayashi, Kenzo

doi:10.1046/j.1365-2036.18.s1.20.x

Cited by 22 publications

(19 citation statements)

References 29 publications

(35 reference statements)

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“…A number of studies have shown that rebamipide, a gastroprotective agent, is effective for the treatment and prevention of gastric ulceration and mucosal damage in vivo (8,(10)(11)(12)(13)(16)(17)(18)(19). Although some reports revealed the molecular mechanism underlying the protective effect of rebamipide in vitro (14,22,23), the precise mechanism remains to be identified.…”

Section: Discussionmentioning

confidence: 96%

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Gastroprotective Agent Rebamipide Induces Cyclooxygenase-2 (COX-2) in Gastric Epithelial Cells

et al. 2005

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Cyclooxyngease-2 (COX-2) is a key enzyme in prostaglandin (PG) synthesis, and COX-2 induction plays an important role in the healing of gastric ulceration. Rebamipide is a gastro-protective agent and attenuates the activity of neutrophils. A number of reports have shown that rebamipide treatment increases PG production in the gastric mucosa {in vivo}. Although its clinical significance in ulcer healing has been demonstrated, {in vitro} evidence remains to be accumulated. Non-transformed rat gastric mucosal cells (RGM1 cells) were stimulated with rebamipide. RT-PCR and Western blot analysis revealed time and dose-dependent transcriptional and translational stimulation of COX-2. PGE(2) was also produced dose-dependently. However, marked COX-2 induction by rebamipide was transient and lasted less than 24 hr. COX-1 expression was unaltered by rebamipide. Reporter assay results confirmed the stimulation of Cox-2 promoter activity by rebamipide. In conclusion, this study provides {in vitro} evidence that rebamipide transcriptionally induces COX-2 and supports the rationale for its clinical use.

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Section: Discussionmentioning

confidence: 96%

“…Clinically, a randomized double-blind controlled study revealed that the use of rebamipide resulted in a marked decrease in inflammation in the gastric mucosa (11). Rebamipide accelerated healing and reduced re-lapse of acetic acidinduced gastric ulcer in rats (12).…”

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confidence: 99%

Gastroprotective Agent Rebamipide Induces Cyclooxygenase-2 (COX-2) in Gastric Epithelial Cells

et al. 2005

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“…Preclinical data has demonstrated various mechanisms involved in rebamipide effects on H. pylori-associated gastritis, including disturbance of the adhesion of H. pylori to gastric epithelial cells and inhibitory effects on H. pylori-induced neutrophil activation or interleukin-8 secretion [6][7][8]. A few reports have even suggested that rebamipide may have a potential anti-H. pylori role [9] while this was not confirmed in large clinical trials [10]. However, we still lack clinical data on rebamipide for the treatment of H. pylori-related gastritis.…”

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confidence: 94%

Anti-inflammatory Effects of Rebamipide According to Helicobacter pylori Status in Patients with Chronic Erosive Gastritis: A Randomized Sucralfate-Controlled Multicenter Trial in China—STARS Study

Zhan

et al. 2008

Dig Dis Sci

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The aim of the study was to investigate the effects of rebamipide on symptom, histology, endogenous prostaglandin, and mucosal oxygen free radicals in chronic erosive gastritis (CEG) patients by using sucralfate as a control. The trial also examined whether Helicobacter pylori infection would affect rebamipide-induced protection. A total of 453 endoscopy-confirmed CEG patients from 11 hospitals in China were enrolled in the study. They randomly received either rebamipide (100 mg t.i.d) or sucralfate (1.0 t.i.d) for 8 weeks with a ratio of 3:1. Per-protocol analysis (n = 415) showed the accumulated symptom score in the rebamipide group dropped from 5.54 +/- 0.97 to 0.80 +/- 0.47 after 8 weeks (P < 0.001 versus control). The endoscopic inflammation score in rebamipide group also decreased from 2.65 +/- 0.09 to 0.60 +/- 0.10, which showed better effects than sucralfate. It was shown a significant improvement (P < 0.01) in prostaglandin E2 (PGE(2)) contents in rebamipide-treated subjects mucosa (225.4 +/- 18.3 pg/g versus 266.7 +/- 14.7 pg/g) compared with that in sucralfate group after 8 weeks of treatment. Malondialdehyde (MDA) contents were significantly depressed both in the trial and control group. When Helicobacter pylori infection was considered, no statistically difference was found in the effect of rebamipide on either symptom or inflammation scores. In conclusion, Rebamipide demonstrated a stronger suppressive effect on the mucosal inflammation in chronic erosive gastritis than sucralfate. The gastroprotection induced by rebamipide is not influenced by H. pylori infection, which indicates its usage in the treatment of H. pylori-associated CEG.

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“…Kim et al [137] observed as it altered the infl ammatory response in human gastric epithelial cell lines infected with CagA+ H. pylori , inhibiting the activation of NF-B and in turn blocked both the transcription and expression of the IL-8 gene. Similarly, rebamipide which displays anti-infl ammatory gastric properties and stimulates the synthesis of endogenous prostaglandins in the gastric mucosa [138] , was shown to be capable of reducing mucosal infl ammation even in the absence of H. pylori eradication [139] . Both these drugs therefore represent potential candidates as add-on medication to eradication regimens.…”

Section: Rescue Therapies After Two or More Failuresmentioning

confidence: 99%

‘Rescue’ Therapies for the Management of <i>Helicobacter pylori </i>Infection

Mario¹,

Cavallaro²,

Scarpignato

2006

Dig Dis

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Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer and gastric cancer and should be considered as a major public health issue. According to several international guidelines, first-line therapy for treating H. pylori infection consists of proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) with any two antibiotics of amoxicillin, clarithromycin or metronidazole given for 7–14 days. However, even with the recommended treatment regimens, approximately 20% of patients will fail to obtain H. pylori eradication. The proportion of patients with first-line H. pylori therapy failure may be higher in clinical practice and it may increase thanks to diffusion of H. pylori treatment. The recommended second-line therapy is the quadruple regimen composed by tetracycline, metronidazole, bismuth salts and a PPI. However, the efficacy of this regimen is limited by poor patient’s compliance due to its side effects, number of tablets per day, and long duration. Moreover, bismuth and metronidazole are not available in all countries. Alternatively, a longer-lasting (i.e. 10–14 days) PPI or RBC triple therapy with two antibiotics has generally been used. In an empirical strategy, the choice of second line depends on the treatment initially used. If a clarithromycin-based regimen was administered in first line, a quadruple regimen or PPI (or RBC) triple therapy with metronidazole and amoxicillin (or tetracycline) should be suggested as a second line. In case of second-line treatment failure, the patient should be evaluated by a case-by-case approach. A susceptibility-guided strategy, if available, is recommended in order to choose the best third-line treatment. Culture can reveal the presence of H. pylori-sensitive strains to clarithromycin (the best effective) or other antimicrobials (such as amoxicillin, metronidazole and tetracycline). Conversely, in an empirical strategy, a third-line not yet used therapy, can reach a high success rate. PPI or RBC, amoxicillin and a new antimicrobial (e.g. rifabutin, levofloxacin or furazolidone) could be used. Several studies have obtained relatively good results with triple therapy combining PPI, rifabutin, and amoxicillin, although a reversible myelotoxicity as leukopenia and thrombocytopenia has been described. Preliminary good results were also achieved with triples PPI regimens combining levofloxacin and amoxicillin without important adverse effects. Furazolidone has also shown efficacy for H. pylori eradication, although untoward reactions could limit its use, especially when high doses are employed. Finally, in more than one H. pylori treatment failure, non-antimicrobial add-on medications (such as lactoferrin, probiotics and others) could be used with the aim either to improve the eradication rate or to minimize side effects.

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Effects of rebamipide, a gastro‐protective drug on the Helicobacter pylori status and inflammation in the gastric mucosa of patients with gastric ulcer: a randomized double‐blind placebo‐controlled multicentre trial

Cited by 22 publications

References 29 publications

Gastroprotective Agent Rebamipide Induces Cyclooxygenase-2 (COX-2) in Gastric Epithelial Cells

Gastroprotective Agent Rebamipide Induces Cyclooxygenase-2 (COX-2) in Gastric Epithelial Cells

Anti-inflammatory Effects of Rebamipide According to Helicobacter pylori Status in Patients with Chronic Erosive Gastritis: A Randomized Sucralfate-Controlled Multicenter Trial in China—STARS Study

‘Rescue’ Therapies for the Management of <i>Helicobacter pylori </i>Infection

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