Efficacy and safety of topical 2% rebamipide ophthalmic suspension in dry eye disease at tertiary care centre

Purpose: To evaluate the effect and side effects of topical 2% rebamipide ophthalmic suspension in dry eye disease. Method: This prospective randomized case control study included total 80 patients (40 cases and 40 controls) of dry eye. Symptoms were graded according to OSDI scoring system and specific tests for dry eye included Tear film breakup time (TBUT), Schirmer’s test, Fluorescein corneal staining (FCS), Rose Bengal staining) were performed. Case group received 2% rebamipide ophthalmic suspension four times daily and control group given carboxymethylcellulose 0.5% four times daily. The follow ups had done at two, six and twelve weeks. Results: The maximum numbers of patients were between 45-60 years. Patient with mild moderate and severe OSDI Score shows marked improvement. Mild TBUT score showed improvement but statistically not significant (P value-0.34). In moderate and severe TBUT Score statistically significant improvement (P value- 0.0001, 0.0001). In all grade FCS shows statistically significant improvement with p value-0.0001, 0.0001, and 0.028 respectively. Schirmer’s test score in all cases had shown improvement but statistically not significant and P value were 0.09, 0.07, and 0.07 respectively. In mild, moderate and severe Rose Bengal staining statistically significant improvement (P value -0.027, 0.0001, and 0.04) .The only side effect was dysgeusia (10% patients). Conclusion: Rebamipide 2% ophthalmic suspension showed significant improvement in symptoms and signs of dry eye. It able to modify epithelial cell function, improve tear stability, and suppress inflammation suggests that it may be a first drug of choice for severe dry eye disease.

Pharmaceutical analysis for a patient with rebamipide-induced Stevens-Johnson syndrome by clinical pharmacists / 中国药房

OBJECTIVE To provide reference for the diagnosis and treatment of Stevens-Johnson syndrome caused by rebamipide， and to explore the predisposing factors of Stevens-Johnson syndrome. METHODS Clinical pharmacists analyzed the treatment process of a patient with gastrointestinal diseases and evaluated the correlation between the drug used and adverse reactions， in order to determine the suspected allergenic drug causing Stevens-Johnson syndrome. The predisposing factors of patients with Stevens-Johnson syndrome were explored. RESULTS & CONCLUSIONS The suspected allergenic drugs that caused the patient to develop Stevens-Johnson syndrome included Ilaprazole enteric-coated tablets， Rebamipide tablets and Kangfuxin liquid. In summary， the suspect drug was identified as Rebamipide tablets according to the causality evaluation method of the National Center for Adverse Drug Reaction Monitoring， Naranjo’s scoring method and the algorithm of drug causality for epidermal necrolysis scoring criteria. Hypoproteinemia， competitive binding of plasma proteins between drugs， advanced age， bacterial and viral infections were the predisposing factors of Stevens-Johnson syndrome. Therefore， before using rebamipide in clinical practice， it is necessary to inquire about the patient’s allergy history in detail. During the use process， it is necessary to strengthen the patient’s medication monitoring and be alert to the occurrence of serious adverse reactions. If any abnormalities are found， the medication should be stopped immediately and symptomatic treatment should be given as soon as possible to ensure the safety and effectiveness of the patient’s medication.

Effect of rebamipide on the acute gouty arthritis in rats induced by monosodium urate crystals / 北京大学学报(医学版)

OBJECTIVE@#To investigate the role of rebamipide in the treatment of acute gout arthritis rats induced by monosodium urate (MSU) crystal.@*METHODS@#Forty-two male rats were randomly divided into three groups (n=14). Group A was treated with oral rebamipide, group B with oral colchicine, and group C with oral placebo. The rats were monitored for the induction of arthritis with clinical manifestations and pathological changes, and the levels of interleukin (IL)-1β、IL-6、IL-10, and tumor necrosis factor (TNF)-α in serum were measured.@*RESULTS@#In group C, the clinical score and swelling index reached the maximum in 24 h, and then gradually decreased to 72 h. After 24 h of model induced, the clinical scores in group C were significantly higher than those in group A and group B [2 (1-3) vs. 0 (0-1) vs. 1 (0-2), P < 0.01], the swelling indexes in group C were significantly higher than those in group A and group B [0.36 (0.16-0.52) vs. 0.11 (0-0.20) vs. 0.12 (0-0.16), P < 0.01]. Histologically, after 24 h of model induced, there was a large number of neutrophil infiltration in the synovium of group C [scale score: 4 (2-4)], and there was no significant inflammatory cell infiltration in group A [1 (0-2)] and group B [1 (0-2)], the difference was statistically significant (P < 0.001). After 24 h of model induced, the levels of IL-1β, IL-6, IL-10, and TNF-α in serum of group C were significantly higher than those in group A and B [IL-1β: (41.86±5.72) vs. (27.35±7.47) vs. (27.76±5.28) ng/L, IL-6: (1 575.55±167.11) vs. (963.53±90.22) vs. (964.08±99.31) ng/L, IL-10: (37.96±3.76) vs. (21.68±4.83) vs. (16.20±2.49) ng/L, TNF-α: (21.32±1.34) vs. (15.82±2.54) vs. (17.35±7.47) μg/L, P < 0.001].@*CONCLUSION@#Rebamipide has a protective effect on acute gout arthritis rats induced by MUS crystals.

The glycocalyx barrier function in ocular surface and its alteration in dry eye disease / 国际眼科杂志(Guoji Yanke Zazhi)

@#Some studies have shown that the glycocalyx barrier formed by highly glycosylated mucin and galectin-3 in the epithelial cells of the eyeball is important for the maintenance of moisturization and lubrication of the surface of the eye. The decrease in the wettability of the eye surface and the shortening of the tear film breakup time in dry eye patients are closely related to the damage of the glycocalyx barrier. This article outlines the composition of the glycocalyx barrier on ocular surface and its changes in the dry eye patients. It will also introduce a new method for assessing the damage of the glycocalyx barrier in dry eye patients. Finally, two ophthalmological drugs, which target regulating the abnoemality of transmembrane mucins in dry eye disease will be mentioned.

Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease

BACKGROUND/AIMS: The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). METHODS: GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. RESULTS: The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. CONCLUSIONS: Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms.

The Efficacy of Rebamipide or Ecabet Sodium Supplementation for Helicobacter pylori Eradication Therapy Compared with Quadruple (Concomitant) Regimen / 대한소화기학회지

BACKGROUND/AIMS: Although some previous studies reported that a treatment combined with mucoprotective agent could improve the eradication rate in dual or triple therapy, there are other reports that question the efficacy of combining these drugs in concomitant therapy (CoCTx). The aim of this study was to investigate the effects of rebamipide or ecabet on the Helicobacter pylori (H. pylori) eradication combined with CoCTx. METHODS: We retrospectively reviewed the medical records of 277 patients with proven H. pylori infection. They were assigned to one of 3 regimens for 10 days, twice daily: (a) CoCTx (n=118): lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg; (b) CoCTx+rebamipide (100 mg) (n=85); (c) CoCTx+ecabet (1 g) (n=74). RESULTS: The baseline characteristics were not significantly different. H. pylori eradication rates were 82.2% (97/118) in CoCTx, 90.6% (77/85) in CoCTx+rebamipide, and 89.2% (66/74) in CoCTx+ecabet (p=0.17), which were statistically insignificant. Overall adverse events were more frequently reported in the CoCTx+rebamipide (50.6%. 43/85) and CoCTx+ecabet (44.6%, 33/74) groups than in the CoCTx (32.2%, 38/118) (p = 0.03) group. Drug compliances were not different between three groups (CoCTx: 95.8%, 113/118; CoCT+rebamipide: 92.9%, 79/85; CoCTx+ecabet 98.6%,73/74) (p=0.209). Multivariate analysis showed that the risk of eradication failure was significantly increased with decreased drug compliance (odds ratio 3.52, 95% confidence interval 1.00–12.32; p=0.05). CONCLUSIONS: Addition of these mucoprotective agent was not superior to CoCTx alone for eradicating H. pylori infection with frequent adverse events. Rather, drug compliance is the most related factor affecting the eradication rate. Our data suggest the importance of drug compliance over the drugs used.

Rebamipide repairs injury of small intestinal epithelial barrier induced by aspirin in mice / 中国病理生理杂志

AIM:To investigate whether rebamipide repairs the small intestinal epithelial barrier in aspirin-induced small intestinal injury (SII) in mice and its mechanism.METHODS:Small intestinal injury was induced by aspirin (200 mg · kg-1 · d-1 for 5 d) in BALB/c mice.Based on the treatment with aspirin and/or rebamipide (320 mg ·kg-1 · d-1),the mice were divided into 4 groups (n =18 in each group).The living mice in each group (n =6) were sacrificed via cervical dislocation method at day 0,day 5,and day 10.The structure and function of intestinal barrier and the levels of the signaling pathway factors were measured by transmission electron microscopy,immunohistochemistry,qPCR,and Western blot.RESULTS:Tight junctions between intestinal epithelial cells improved significantly after rebamipide treatment.The expression of ZO-1 and occludin in the injured small intestine showed a gradually increasing trend after rebamipide administration (P ＜ 0.05).There was a decreased trend of D-lactate level in rebamipide-treated SII mice (P ＜ 0.05).The expression of cyolooxygenase-2 (COX-2),β-catenin,and c-Myc,and prostaglandin E2 concentration in small intestinal tissues were significantly increased in rebamipide treatment group (P ＜ 0.05).However,down-regulated COX-1 expression in the SII mice was sustained at a low level after rebamipide administration.CONCLUSION:Rebamipide repairs the injury of small intestinal mucosa and improves the structure and function of small intestinal barrier in aspirininduced SII mice by up-regulating the expression of COX-2.

Metabolomics Approach to Explore the Effects of Rebamipide on Inflammatory Arthritis Using Ultra Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry

OBJECTIVE: Rebampide is a gastroprotective agent used to treat gastritis. It possesses anti-inflammatory and anti-arthritis effects, but the mechanisms of these effects are not well understood. The objective of this study was to explore mechanisms underlying the therapeutic effects of rebamipide in inflammatory arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in DBA/1J mice. DBA/1J mice were immunized with chicken type II collagen, then treated intraperitoneally with rebamipide (10 mg/kg or 30 mg/kg) or vehicle (10% carboxymethylcellulose solution) alone. Seven weeks later, plasma samples were collected. Plasma metabolic profiles were analyzed using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics study and metabolite biomarkers were identified through multivariate data analysis. RESULTS: Low dose rebamipide treatment reduced the clinical arthritis score compared with vehicle treatment, whereas high dose rebamipide in CIA aggravated arthritis severity. Based on multivariate analysis, 17 metabolites were identified. The plasma levels of metabolites associated with fatty acids and phospholipid metabolism were significantly lower with rebamipide treatment than with vehicle. The levels of 15-deoxy-Δ¹²,¹⁴ prostaglandin J2 and thromboxane B3 decreased only in high dose-treated groups. Certain peptide molecules, including enterostatin (VPDPR) enterostatin and bradykinin dramatically increased in rebamipide-treated groups at both doses. Additionally, corticosterone increased in the low dose-treated group and decreased in the high dose-treated group. CONCLUSION: Metabolomics analysis revealed the anti-inflammatory effects of rebamipide and suggested the potential of the drug repositioning in metabolism- and lipid-associated diseases.

Clinical Observation of Rebamipide Triple Therapy in the Treatment of Gastric Ulcer with Bleeding / 中国药房

OBJECTIVE:To observe the efficacy and safety of rebamipide triple therapy in the treatment of gastric ulcer with bleeding. METHODS:130 patients with gastric ulcer with bleeding were randomly divided into control group(65 cases)and obser-vation group(65 cases). Control group received Omeprazole enteric-coated capsule 20 mg,orally,twice a day+Aluminum magne-sium carbonate tablet 500 mg,orally,once a day;observation group was additionally received Rebamipide tablet 0.1 g,orally,3 times a day. They were treated for 12 weeks. Clinical efficacy,remission time of belching,abdominal pain,bloating,hematemesis/hematochezia,clinical symptom score before and after treatment,rebleeding and the incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,remission time of symptoms and signs were significantly shorter than control group,the incidence of rebleeding was significantly lower than con-trol group,with statistical significances (P0.05). After treatment,the clinical symptom scores in 2 groups were significantly lower than before,and observation group was lower than control group,with statistical significances (P0.05). CONCLUSIONS:Rebamipide triple therapy shows obvious short-term efficacy in the treat-ment of gastric ulcer with bleeding,which can effectively improve patients'gastrointestinal symptoms,reduce rebleeding risk,and does not increase the incidence of adverse reactions.

Rebamipide repairs injury of small intestinal epithelial barrier induced by aspirin in mice / 中国病理生理杂志

AIM:To investigate whether rebamipide repairs the small intestinal epithelial barrier in aspirin-induced small intestinal injury (SII) in mice and its mechanism.METHODS:Small intestinal injury was induced by aspirin (200 mg · kg-1 · d-1 for 5 d) in BALB/c mice.Based on the treatment with aspirin and/or rebamipide (320 mg ·kg-1 · d-1),the mice were divided into 4 groups (n =18 in each group).The living mice in each group (n =6) were sacrificed via cervical dislocation method at day 0,day 5,and day 10.The structure and function of intestinal barrier and the levels of the signaling pathway factors were measured by transmission electron microscopy,immunohistochemistry,qPCR,and Western blot.RESULTS:Tight junctions between intestinal epithelial cells improved significantly after rebamipide treatment.The expression of ZO-1 and occludin in the injured small intestine showed a gradually increasing trend after rebamipide administration (P ＜ 0.05).There was a decreased trend of D-lactate level in rebamipide-treated SII mice (P ＜ 0.05).The expression of cyolooxygenase-2 (COX-2),β-catenin,and c-Myc,and prostaglandin E2 concentration in small intestinal tissues were significantly increased in rebamipide treatment group (P ＜ 0.05).However,down-regulated COX-1 expression in the SII mice was sustained at a low level after rebamipide administration.CONCLUSION:Rebamipide repairs the injury of small intestinal mucosa and improves the structure and function of small intestinal barrier in aspirininduced SII mice by up-regulating the expression of COX-2.

Effects of Rebamipide on Gastrointestinal Symptoms in Patients with Type 2 Diabetes Mellitus

BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with type 2 diabetes mellitus (T2DM). Rebamipide is an effective gastric cytoprotective agent, but there are few data on its usefulness in T2DM. The aim of this study is to evaluate the improvement of GI symptoms after rebamipide treatment in patients with T2DM. METHODS: Patients with T2DM and atypical GI symptoms were enrolled. They took rebamipide (100 mg thrice daily) for 12 weeks and filled out the diabetes bowel symptom questionnaire (DBSQ) before and after rebamipide treatment. The DBSQ consisted of 10 questions assessing the severity of GI symptoms by a 1 to 6 scoring system. Changes in the DBSQ scores before and after rebamipide treatment were analyzed to evaluate any improvements of GI symptoms. RESULTS: A total of 107 patients were enrolled, and 84 patients completed the study. The mean age was 65.0±7.8, 26 patients were male (24.8%), the mean duration of T2DM was 14.71±9.12 years, and the mean glycosylated hemoglobin level was 6.97%±0.82%. The total DBSQ score was reduced significantly from 24.9±8.0 to 20.4±7.3 before and after rebamipide treatment (P<0.001). The DBSQ scores associated with reflux symptoms, indigestion, nausea or vomiting, abdominal bloating or distension, peptic ulcer, abdominal pain, and constipation were improved after rebamipide treatment (P<0.05). However, there were no significant changes in symptoms associated with irritable bowel syndrome, diarrhea, and anal incontinence. No severe adverse events were reported throughout the study. CONCLUSION: Rebamipide treatment for 12 weeks improved atypical GI symptoms in patients with T2DM.

The Benefits of Combination Therapy with Esomeprazole and Rebamipide in Symptom Improvement in Reflux Esophagitis: An International Multicenter Study

BACKGROUND/AIMS: To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. METHODS: A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. RESULTS: The mean decreases in the total symptom score at 4 weeks were estimated to be −18.1±13.8 in the combination therapy group and −15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were −8.4±6.6 in the combination therapy group and −6.8±5.9 in the monotherapy group (p=0.009). CONCLUSIONS: Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.

The Benefits of Combination Therapy with Esomeprazole and Rebamipide in Symptom Improvement in Reflux Esophagitis: An International Multicenter Study

BACKGROUND/AIMS: To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. METHODS: A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. RESULTS: The mean decreases in the total symptom score at 4 weeks were estimated to be −18.1±13.8 in the combination therapy group and −15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were −8.4±6.6 in the combination therapy group and −6.8±5.9 in the monotherapy group (p=0.009). CONCLUSIONS: Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.

Protective Effect and Mechanism of Rebamipide on Injury of Human Colon Cancer Cell Line Caco-2 Induced by Aspirin / 胃肠病学

Background:With the development of capsule endoscopy,small intestinal injury induced by non-steroidal anti-inflammatory drugs( NSAIDs)has become an issue of growing concern. Although there are a variety of drugs used for NSAIDs-induced gastric mucosal injury,small intestinal injury caused by NSAIDs is lack of effective prevention and treatment modalities. Aims:To investigate the protective effect and possible mechanism of rebamipide on human colon cancer cell line Caco-2 injury induced by aspirin. Methods:In aspirin group,Caco-2 cells were treated with aspirin 10 mmol/L;in rebamipide group,Caco-2 cells were treated with aspirin and different concentrations of rebamipide(0. 1, 0. 5,1. 0 mmol/L),and a negative control group was established. Cell proliferation inhibition was measured by MTT assay. Cell apoptosis was determined by flow cytometry. Morphological changes of cells were observed under inverted phase contrast microscope. Permeability of cells was assessed by Transwell assay. Expressions of tight junction proteins occludin and zonula occluden-1(ZO-1),as well as mitogen activated protein kinase(MAPK)signaling pathway-associated proteins including extracellular signal-regulated kinase(ERK)1/2,phosphorylated ERK1/2(p-ERK1/2),p38,p-p38,c-Jun N-terminal kinase( JNK),and p-JNK,were determined by Western blotting. Results:Proliferation inhibition rate,apoptosis rate and permeability of Caco-2 cells in rebamipide 0. 1,0. 5,1. 0 mmol/L groups were significantly lower than those in aspirin group in a dose-dependent manner(P<0. 05). Injuries of Caco-2 cells were seen in aspirin group by inverted phase contrast microscope and rebamipide could reduce these injuries. Expressions of occludin,ZO-1 and p-JNK were significantly higher and expressions of p-p38 and p-ERK1/2 were significantly lower in rebamipide 0. 1,0. 5,1. 0 mmol/L groups than those in aspirin group in a dose-dependent manner(P<0. 05). Conclusions:Rebamipide have a protective effect against aspirin-induced Caco-2 cell injury,probably through regulating MAPK signaling pathway( inhibiting p38 and ERK1/2 phosphorylation,stimulating JNK phosphorylation),and subsequently up-regulating the expressions of tight junction proteins and decreasing the permeability of cells.

Preventive Efficacy and Safety of Rebamipide in Nonsteroidal Anti-Inflammatory Drug-Induced Mucosal Toxicity

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.

Protective effects and its mechanism of rebamipide on aspirin-induced injury in human gastric mucosal epithelium cells / 中华消化杂志

Objective To investigate the protective effects and its mechanism of rebamipide on aspirin-induced injury in human gastric mucosal epithelium cells (GES-1).Methods GES-1 cells monolayer culture model was established in vitro.Then the cells were divided into negative control group,aspirin injured group and combination of rebamipide at different concentration (0.2,0.5,1.0 mrnol/L) and aspirin groups.The cell proliferation,the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) of each group were detected.The ultrastructural changes of each group were observed by transmission electron microscopy (TEM).The expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) at protein level in the cells of each group were detected by Western blot.Nrf2 interfering suppression test was performed and then the influence of Nrf2 small interfering RNA (siRNA) on the expression of HO-1 protein was observed.One-way analysis of variance was performed for comparison among multi-groups and t-test was used for comparison between the two groups.Results The cell viability of aspirin injured group and combination of rebamipide at different concentration (0.2,0.5,1.0 mmol/L) and aspirin groups were (49.56±3.88)％,(59.34±4.36) ％,(70.79 ± 5.96) ％ and (86.07 ± 5.20) ％,respectively,and the difference was statistically significant (F=30.634,P＜ 0.01).Compared with aspirin injured group,the content of MDA significantly lowered in combination of rebamipide at different concentration (0.2,0.5,1.0 mmol/L) and aspirin groups ((2.26±0.25) nrnol/rng vs (1.85±0.13) nmol/mg vs (1.62±0.11) nmol/mg vs (1.13±0.15) nmol/mg),and the difference was statistically significant (F=23.821,P＜0.05).Compared with aspirin injured group,the activity of SOD significantly increased in combination of rebamipide at 0.5 and 1.0 mmol/L and aspirin groups ((8.49±0.89) U/rng vs (11.50±1.03) U/mg vs (13.74±0.76) U/mg),the difference was statistically significant (F=25.666,P＜0.05).Under TEM,the cell ultrastrucmral was obviously inured in aspirin treated,while rebamipide could relieve the injury.The differences of relative expression quantity of Nrf2 and HO-1 at protein level among combination of rebamipide at 0.2,0.5 and 1.0 mmol/L and aspirin groups and aspirin injured group were statistically significant (0.35±0.04 vs 0.46± 0.05 vs 0.84±0.08 vs 0.15±0.02,0.72±0.09 vs 0.93±0.11 vs 1.29±0.14 vs 0.39±0.07,F=92.550and 38.235,both P＜0.05).After transfected with Nrf2 siRNA,the expression of HO-1 was 0.38±0.04 in aspirin injured group and 0.62±0.08 in combination of rebamipide and aspirin group,which was lower than that before transfection (0.61 ± 0.05,1.33± 0.09),respectively.The differences were statistically significant (t =6.276 and 10.444,both P＜0.05).Conclusion Rebamipide may activate Nrf2/HO-1 pathway and relieve aspiriwinduced oxidative stress in GF1 ceils.

The Effect of Co-Administration of Rebamipide on the Expression of Serum Gastrin in Long-term Proton Pump Inhibitor Users: A Prospective Pilot Study

BACKGROUND/AIMS: In one animal study, co-administration of rebamipide with proton pump inhibitors (PPIs) could suppress hypergastrinemia but there have been no such reports on humans. The aim of this study was to evaluate whether rebamipide could prevent hypergastrinemia in long-term PPI users. MATERIALS AND METHODS: Patients who were diagnosed with reflux esophagitis endoscopically were enrolled in this study. In the control group, lansoprazole 30 mg was administered for 8 weeks and in the rebamipide group, lansoprazole 30 mg with rebamipide 300 mg was administered for 8 weeks. Serum gastrin level was checked before and after administration of the drugs. RESULTS: Thirty patients were enrolled in this study. The control group included 17 patients and the rebamipide group included 13 patients. The gastrin level was elevated in the control group (28.4 pg/mL) compared to the rebamipide group (38.5 pg/mL). However, the gastrin level was decreased in 3 patients in the rebamipide group (23.1%) compared to 2 patients in the control group (11.8%). CONCLUSIONS: Not all patients who are taking PPIs develop hypergastrinemia. Co-administration of rebamipide with PPI does not affect the serum gastrin level.

Effect of omeprazole, rabeprazole, and rebamipide on the accuracy of urea breath test in patients with Helicobacter pylori infection

Background: The urea breath test (UBT) has been widely used for H. pylori eradication after treatment. The breath test could be adversely affected by various factors including proton pump inhibitors (PPIs) that are also used in the therapy for H. pylori infection. Objective: Determine the effect of omeprazole, rabeprazole and the mucoprotective agent rebamipide, on the UBT. Methods: Fifty-six patients with dyspepsia and positive for H. pylori by rapid urease test were enrolled. They were classified into three groups: Group 1 (n=25) received omeprazole 20 mg once daily, group 2 (n=13) received rabeprazole 20 mg once daily, and group 3 (n=18) received rebamipide 100 mg three times a day. All patients received a 14-day course of their medications. UBT was performed on day 0 as a baseline and on day 14 in all patients. In patient with negative results of UBT on day 14, the UBT was performed in consecutive week until the test became positive. Results: Fifty-six patients (20 men and 36 women) participated in the study. Their mean age was 46.77±14.3 years. False negative rate after 14-day treatment in omeprazole, rabeprazole and rebamipide group were 20.0%, 30.8%, and 0% respectively. There was a significant difference between 13C level in patients with negative and positive UBT results (2.7±0.7 vs.22.9±3.7/mL, p=0.025). The reversal of false negative to true positive tests occurred within two weeks after discontinuation of omeprazole and rabeprazole. Conclusion: Proton pump inhibitors had an effect on the accuracy of H. pylori detection using UBT. Rabeprazole revealed a higher false negative rate in the UBT than omeprazole. The mucoprotective drug, rebamipide, did not influence negative results in the UBT.

Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells

Rebamipide a gastroprotective drug, is clinically used for the treatment of gastric ulcers and gastritis, but its actions on gastric cancer are not clearly understood. Phospholipase D (PLD) is overexpressed in various types of cancer tissues and has been implicated as a critical factor in inflammation and carcinogenesis. However, whether rebamipide is involved in the regulation of PLD in gastric cancer cells is not known. In this study, we showed that rebamipide significantly suppressed the expression of both PLD1 and PLD2 at a transcriptional level in AGS and MKN-1 gastric cancer cells. Downregulation of PLD expression by rebamipide inhibited its enzymatic activity. In addition, rebamipide inhibited the transactivation of nuclear factor kappa B (NFkappaB), which increased PLD1 expression. Rebamipide or PLD knockdown significantly suppressed the expression of genes involved in inflammation and proliferation and inhibited the proliferation of gastric cancer cells. In conclusion, rebamipide-induced downregulation of PLD may contribute to the inhibition of inflammation and proliferation in gastric cancer.

Rebamipide May Be Comparable to H2 Receptor Antagonist in Healing Iatrogenic Gastric Ulcers Created by Endoscopic Mucosal Resection: A Prospective Randomized Pilot Study

Endoscopic mucosal resection (EMR) results in the formation of iatrogenic gastric ulcers and the optimal treatments for such ulcers are still unclear. We aimed to evaluate the efficacy of rebamipide in the management of EMR-induced ulcers by comparing it with an H2 receptor antagonist. After EMR, patients were randomly assigned into either rebamipide or famotidine groups. All patients received a one-week lansoprazole 30 mg q.d. therapy followed by three-week famotidine (20 mg b.i.d.) or rebamipide (100 mg t.i.d.) therapy. Four weeks after the treatments, ulcer sizes, stages, bleeding rates, and ulcer-related symptoms were compared using endoscopy and a questionnaire. A total of 63 patients were enrolled in this study. Finally, 51 patients were analyzed, 26 in rebamipide and 25 in famotidine group. Baseline characteristics were not significantly different between the two groups. Four weeks after EMR, the two groups were comparable in terms of ulcer reduction ratio (P=0.297), and ulcer stage (P=1.000). Moreover, no difference was observed with regard to ulcer-related symptoms, drug compliance, adverse drug event rates, and bleeding rates. Our data suggest that rebamipide is not inferior to famotidine in healing iatrogenic gastric ulcers, and could be a therapeutic option in the treatment of such ulcers.