Rebamipide Group Research Articles

The Effect of Topical Rebamipide 2% in Managing Dry Eye Following Cataract Surgery

Purpose: To evaluate the potential advantages of using topical rebamipide 2% to manage dry eye following cataract surgery.Methods: Patients who underwent cataract surgery (phacoemulsification and intraocular lens insertion) were evaluated for dry eye 1 week postoperatively. Randomly selected patients were divided into the rebamipide group, who received 2% rebamipide eye drops, and the control group, who did not receive rebamipide. Various dry eye-related tests, including Schirmer’s test, the tear break-up time (TBUT), ocular surface staining, tear film osmolarity, tear lipid layer thickness, and the ocular surface disease index (OSDI) were performed in both groups 1 week, and 1 and 2 months postoperatively.Results: In the rebamipide group, we observed significant improvement in TBUT, the ocular surface staining score, and OSDI at 2 months postoperatively, as compared to 1 week (<i>p</i> = 0.002, 0.014, and 0.013, respectively). Schirmer’s test, tear film osmolarity, and tear lipid layer thickness remained unchanged in the rebamipide group. Throughout the entire follow-up period, the rebamipide group had a significantly prolonged TBUT (1 month: <i>p</i> = 0.007, 2 months: <i>p</i> = 0.000), and lower ocular surface staining score (1 month: <i>p</i> = 0.000, 2 months: <i>p</i> = 0.000), as compared to the control.Conclusions: Following cataract surgery, the use of rebamipide eye drops produced improvements in TBUT, ocular surface staining scores, and OSDI. This suggests that rebamipide offers benefits in managing dry eye that can occur after cataract surgery.

Study the Effect of Adding Rebamipide on the Eradication Therapy for Helicobacter pylori Infection

Abstract Background H. pylori infection is a leading etiological factor for various gastroduodenal diseases, including chronic gastritis, peptic ulcers and duodenal ulcers, as well as adenocarcinoma and MALT lymphoma of the stomach. In the last decad, there has been a negative trend in the effectiveness of classic eradication therapy regimens of H.pylori, which has largely been determined by the emergence and spread of antibiotic resistance. Aim of the Work Study the effect of adding Rebamipide on the eradication therapy for helicobacter pylori infection in Egyptian patients. Patients and Methods This study included 100 patients with H.Pylori infection who had been confirmed by tissue histopathology. Results Regarding the outcome, there was a statistically significant difference between the two groups (p = 0.027) as in Rebamipide group, there was 12% cases had positive results and 88% cases had negative results while in control group, there was 30% cases had positive results and 70% cases had negative results. Regarding side effects, there was no statistically significant difference between the two groups (p = 0.360). one case in Rebamipide group experienced mild skin rash at 1st day of treatment because of allergy to rebamipide and patient was completely free of symptoms after two days without stopping treatment. Conclusion This study demonstrated that the addition of rebamipide to H. pylori eradication regimens significantly increases the effectiveness of treatment. Based on our findings, abdominal discomfort was observed significantly higher in control group, there was a statistically significant difference between the two groups (more to rebamipide group) regarding outcome and there was no statistically significant difference between the two studied groups regarding side effects.

Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial)

ObjectivesThis study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy.Materials and methodsPhase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis.ResultsThere was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group.ConclusionRebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis.Trial registrationThe trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.

Clinical Efficacy of 2% Rebamipide in Patients With Video Display Terminal-Associated Dry Eye Disease: A Prospective, Randomized, Double-Blinded Study.

To compare the effects of 2% rebamipide clear solution and 0.1% sodium hyaluronate eye drops in patients with visual display terminal (VDT)-related dry eye disease (DED). Prospective, randomized, double-blinded Study. This was a prospective, double-blind, and randomized controlled study. Patients with VDT-related DED were randomly allocated to a 2% rebamipide (REB) group or a 0.1% sodium hyaluronate (HYA) group (4 times/day for 4 weeks). The ocular surface disease index (OSDI), dry eye questionnaire-5 (DEQ-5), Placido disk-tear film analyzer, fluorescein-stained tear break-up time (FBUT), ocular surface staining score, and Schirmer 1 test were examined before and after the instillation of drug. A total of 56 eyes of 28 patients (28 eyes of 14 patients in each group) were included. There were no significant differences in the baseline data. The OSDI, DEQ-5, FBUT, and conjunctival erosion scores improved significantly in both groups after treatment. In the REB group, corneal staining and bulbar nasal redness scores also improved significantly after treatment ( P <0.001 and 0.036, respectively), whereas no significant differences were found in these parameters in the HYA group ( P =0.326 and 0.118, respectively). The REB group showed a significantly larger decrease in the corneal staining score than the HYA group ( P =0.016). No adverse reactions were observed. A 2% rebamipide clear solution effectively improved the symptoms and signs in patients with VDT-related DED and was superior to 0.1% sodium hyaluronate ophthalmic solution in improving corneal epithelial damage, making it a safe and effective treatment option for VDT-related DED.

The Efficacy and Safety of Rebamipide Ophthalmic Suspension (OPC-12759) in Patients with Dry Eye Disease: A Systematic Review of Randomized Controlled Trials.

The aim of this paper is to evaluate the efficacy and safety of Rebamipide (REB) ophthalmic suspension in dry eye disease (DED). A systematic review that only included full-length randomized controlled studies (RCTs) reporting the effects of REB ophthalmic suspension in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The Cochrane risk of bias tool was used to analyze the quality of the studies selected. A total of seven studies were included in this systematic review. Although the overall risk of bias was low, most studies were sponsored by the manufacturer. REB ophthalmic suspension treatment achieved higher improvement than the control group in all reported variables. The mean differences between both groups were in favor of the REB group and were as follows: dry eye-related quality of life score (DEQS) -3.5 ± 2.9 points, tear film break-up time (TBUT) of 0.7 ± 0.6 s, Schirmer test (ST) without anesthesia of 0.3 ± 0.6 mm and total corneal fluorescein staining (tCFS) of -1.2 ± 0.7 points. Adverse events (AEs) were 5.2 ± 7.6% superior in the REB group, with an overall compliance > 95%. Therefore, REB ophthalmic suspension is a safe and effective treatment that could be recommended in patients with DED.

Efficacy and safety of 1% and 2% rebamipide clear solution in dry eye disease: a multicenter randomized trial

BackgroundTo evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED).MethodsTwo hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment.ResultsThe mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (− 3.15±2.00) at 12 weeks from baseline than the placebo group (− 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups.Conclusions1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.

Effectiveness of Rebamipide as a part of the &lt;i&gt;Helicobacter pylori&lt;/i&gt; eradication therapy in Russia: a meta-analysis of controlled trials

Aim. To perform a meta-analysis of the data on Rebamipide efficacy and safety as a part of Helicobacter pylori eradication therapy in Russian patients.&#x0D; Materials and methods. A search for original studies was conducted in the electronic database of the Russian Science Citation Index (RSCI) on the Scientific Electronic Library (SEL Elibrary.ru). Google (Google.com) was used for the "grey" search. All Russian controlled studies comparing the efficacy and/or safety of Rebamipide as a part of the regimen of H. pylori eradication therapy were included in the final analysis.&#x0D; Results. In 6 included controlled trials with a cumulative population (considering double comparisons between multiple groups) of 531 patients (273 in Rebamipide groups and 258 in groups without Rebamipide), the pooled eradication effectiveness was 90.376% (95% confidence interval CI 86.31193.560) in patients receiving Rebamipide and 81.681% (95% CI 76.49986.141) in patients receiving eradication regimens without Rebamipide. The meta-analysis showed that the Rebamipide addition to eradication regimens significantly improved efficacy (odds ratio 2.162, 95% CI 1.2683.685; p=0.005). No significant heterogeneity was found between study results (p=0.863; I2=0.00%); therefore, a fixed effects model was used in the resulting analysis. In addition, the meta-analysis of included studies showed a reduction of adverse events (odds ratio 0.569, 95% CI 0.3330.970) in the groups receiving Rebamipide; p=0.038). This effect of Rebamipide deserves special attention and requires additional study, as the result was at the border of statistical significance in the subanalysis of three studies with a large margin of risk reduction in one of them (with the largest sample of patients).&#x0D; Conclusion. The present meta-analysis demonstrated that the Rebamipide addition to H. pylori eradication regimens significantly improves the treatment effectiveness in the Russian patient population.

Effect of Rabeprazole and Rebamipide in the Treatment of Upper Gastrointestinal Hemorrhage Associated with Dual Antiplatelet Therapy in Elderly Patients with Coronary Heart Disease.

To investigate the therapeutic effect of rabeprazole and rebamipide on patient age over 60 with dual antiplatelet therapy (DAPT)-related upper gastrointestinal hemorrhage following percutaneous coronary intervention (PCI). A total of 360 patients age over 60 undergoing PCI were recruited for antiplatelet therapy involving a combined treatment of aspirin (100 mg/d) and clopidogrel (75 mg/d). The enrolled patients were divided into 4 groups: the control group, the rabeprazole group, the rebamipide group, and the rabeprazole + rebamipide group. The incidence and severity of any upper gastrointestinal hemorrhage and the incidence of major adverse cardiac events (MACEs) were observed 6 months after the operation. The incidence of upper gastrointestinal hemorrhage in the 4 groups was 11.1%, 3.3%, 8.9%, and 1.1%, respectively, and the differences were statistically significant (P < 0.05). On comparing the groups, the differences between the control group and the rabeprazole group, those between the control group and the rabeprazole + rebamipide group, and those between the rebamipide group and the rabeprazole + rebamipide group were found to be statistically significant (P < 0.05). The severity of the upper gastrointestinal hemorrhage in the rabeprazole group and the rabeprazole + rebamipide group was significantly lower than that in the control group. The 4 groups exhibited no significant differences in the incidence of MACEs (P > 0.05). For patients age over 60 receiving DAPT following PCI in our study population, treatment with rabeprazole or a combination of rabeprazole and rebamipide could reduce the risk of upper gastrointestinal hemorrhage, as well as reduce its severity.

Post exenteration prosthetic rehabilitation in mucormycosis cases: Tips and tricks

Oral sub mucous fibrosis (OSF) is commonly seen in the Indian subcontinent affecting individuals of all age groups. It is a potentially malignant disorder caused almost exclusively by the use of smokeless form of tobacco products. The malignant transformation rates vary from 3 to 19%. The standard of care (SOC) in managing OSF includes habit cessation, intralesional steroid and hyaluronidase injections, and mouth opening exercises. To evaluate the efficacy of rebamipide to reduce the oral burning sensation associated with OSMF as compared to coventional Betamethasone intralesional injection.After providing information about the study and obtaining consent, these individuals were divided into two groups of 15 each using random sampling method. Patients in the rebamipide group (group I) were prescribed 100 mg tablets of rebamipide thrice a day for 21 days. The other 15 patients (group II) were given SOC, intralesional betamethasone injection 4 mg/mL once a week for 4 weeks. Visual analog scale (VAS) with 11 points (0–10) was used to assess burning sensation in the first visit, and change in the burning sensation was assessed after every 7th day on VAS in both the groups.: The improvement in the VAS score in each visit was significant (p &amp;#60; 0.05) in the 1st, 2nd, 3rd, and 4th visit. The VAS score between the 4th and 5th visit failed to reach a statistically significant level (p &amp;#62; 0.05). The VAS score was significantly different between the rebamipide and betamethasone group (p &amp;#62; 0.05) in third &amp; fourth visit. Our results showed that rebamipide was equally efficacious if not better than the betamethasone intralesional injections.

Comparative study of rebamipide & betamethasone in managing stomatopyrosis in oral submucous fibrosis (OSMF) patients

Oral sub mucous fibrosis (OSF) is commonly seen in the Indian subcontinent affecting individuals of all age groups. It is a potentially malignant disorder caused almost exclusively by the use of smokeless form of tobacco products. The malignant transformation rates vary from 3 to 19%. The standard of care (SOC) in managing OSF includes habit cessation, intralesional steroid and hyaluronidase injections, and mouth opening exercises. To evaluate the efficacy of rebamipide to reduce the oral burning sensation associated with OSMF as compared to coventional Betamethasone intralesional injection.After providing information about the study and obtaining consent, these individuals were divided into two groups of 15 each using random sampling method. Patients in the rebamipide group (group I) were prescribed 100 mg tablets of rebamipide thrice a day for 21 days. The other 15 patients (group II) were given SOC, intralesional betamethasone injection 4 mg/mL once a week for 4 weeks. Visual analog scale (VAS) with 11 points (0–10) was used to assess burning sensation in the first visit, and change in the burning sensation was assessed after every 7th day on VAS in both the groups.: The improvement in the VAS score in each visit was significant (p &amp;#60; 0.05) in the 1st, 2nd, 3rd, and 4th visit. The VAS score between the 4th and 5th visit failed to reach a statistically significant level (p &amp;#62; 0.05). The VAS score was significantly different between the rebamipide and betamethasone group (p &amp;#62; 0.05) in third &amp; fourth visit. Our results showed that rebamipide was equally efficacious if not better than the betamethasone intralesional injections.

Comparative Study of Rebamipide & Betamethasone in Managing Stomatopyrosis in Oral Submucous Fibrosis (OSMF) Patients

Background: Oral submucous fibrosis (OSF) is commonly seen in the Indian subcontinent affecting individuals of all age groups. It is a potentially malignant disorder caused almost exclusively by the use of smokeless forms of tobacco products. The malignant transformation rates vary from 3 to 19%. The standard of care (SOC) in managing OSF includes habit cessation, intralesional steroid and hyaluronidase injections, and mouth opening exercises. Objectives: To evaluate the efficacy of rebamipide to reduce the oral burning sensation associated with OSMF as compared to coventional Betamethasone intralesional injection. Materials and Methods: After providing information about the study and obtaining consent, these individuals were divided into two groups of 15 each using random sampling method. Patients in the rebamipide group (group I) were prescribed 100 mg tablets of rebamipide thrice a day for 21 days. The other 15 patients (group II) were given SOC, intralesional betamethasone injection 4 mg/mL once a week for 4 weeks. Visual analog scale (VAS) with 11 points (0–10) was used to assess burning sensation in the first visit, and change in the burning sensation was assessed after every 7th day on VAS in both the groups. Results: The improvement in the VAS score in each visit was significant (p 0.05). The VAS score was significantly different between the rebamipide and betamethasone group (p > 0.05) in the third & fourth visits. Conclusion: Our results showed that rebamipide was equally efficacious if not better than the betamethasone intralesional injections.

Cevimeline-induced anti-inflammatory effect through upregulations of mucins in the ocular surface of a dry eye mouse model

This study aimed to investigate the effects of various concentrations of cevimelines (CVMs) and compare them with commercial drugs in a murine model of dry eye. The experimental mouse model used male and female NOD.B10.H2b mice over 12 weeks of age. Desiccation stress was performed at 30–40% ambient humidity, and subcutaneous injection of 0.5 mg/0.2 mL scopolamine hydrobromide was performed four times a day for 10 days. The efficacy of various concentrations of CVMs (seven experimental groups) was first evaluated, and then 2% CVM was compared with commercial drugs, such as cyclosporine A (CsA), diquafosol (DQS), and rebamipide (REB) (seven experimental groups). The clinical changes, including tear production, corneal irregularity, and fluorescein staining, were measured after the instillation of various concentrations of CVMs and commercial drugs for 0, 3, 5, 7, and 10 days. Histological changes, such as corneal detachment, conjunctival goblet cell and mucin density staining, were assessed by staining the cornea or conjunctiva with hematoxylin-eosin, periodic acid-Schiff, and alcian blue. The expression of inflammatory markers and mucin factors was detected by immunohistochemistry and immunofluorescence in the lacrimal gland, cornea, and conjunctiva. Tear production was significantly increased in the 2% CVM group and was similar to that in the DQS and REB groups (P < 0.05). The corneal smoothness and fluorescein staining score were significantly improved in the 2% CVM group and were similar to those in the REB group (P < 0.05). Corneal epithelial cells were significantly decreased in the 2% CVM group, with similar observations made in the DQS and REB groups (P < 0.05). The conjunctival goblet cells and mucin density recovered in the 2% CVM group were similar to those in the CsA and REB groups (P < 0.05). The 2% CVM group showed suppressed expression of inflammatory factors in the lacrimal gland and was comparable to that seen in the CsA and REB groups. The expression of mucin factors was upregulated in the cornea and conjunctiva of the 2% CVM group and was similar to that of the CsA and REB groups. In conclusion, administration of CVM resulted in recovery or clinical and histological improvement of the murine dry eye model, and all the observed parameters were comparable to those with commercial drugs.

The effect of PPIs Alone, PPIs plus cytoprotective agent, and H2RA plus cytoprotective agent on ulcer healing after endoscopic submucosal dissection: A prospective randomized controlled trial

Background and Study AimsEndoscopic submucosal dissection (ESD) is the most effective treatment for early gastric cancer or gastric adenoma. However, ESD results in iatrogenic ulcers and postoperative bleeding from ulcers. This study aimed to evaluate the effect of using a proton pump inhibitor (PPI) alone, a PPI + rebamipide combination therapy, and an H2 receptor antagonist (H2RA) + rebamipide combination therapy on ulcer healing after ESD. Patients and MethodsA total of 204 patients who underwent ESD from April 2014 to July 2017 at Dong-A University Hospital were randomly assigned to the following groups: PPI-alone group, PPI + rebamipide combination therapy group, and H2RA + rebamipide combination therapy group. However, only 156 patients were studied since we excluded those who were lost to follow-up or had diseases other than early gastric cancer or gastric adenoma. Twenty-eight days after ESD, we evaluated the ulcer residual ratio, S stage rates, ulcer bleeding ratio, and gastric pH. ResultsThis study included 156 patients (PPI-alone group: 52 patients; PPI + rebamipide group: 52 patients; H2RA + rebamipide group: 52 patients). The ulcer residual ratios were 24.3 ± 14.2%, 17.0 ± 12.1%, and 21.0 ± 13.8% in the PPI alone, PPI + rebamipide, and H2RA + rebamipide groups, respectively (P = 0.048). ConclusionsPPI + rebamipide was more effective in reducing the ulcer residual ratio after ESD. There was no statistical difference in ulcer stage and delayed bleeding after ESD among the groups. These findings showed that PPI + rebamipide had limited benefits after ESD.

A comparative study of rebamipide 2% and carboxy methylcellulose (CMC) 0.5% eye drop in patients with dry eyes: A randomized, hospital-based study

Aim: To compare the efficacy of 2% rebamipide and 0.5% Carboxy methylcellulose (CMC) eye drops in dry eye patients. Materials and Methods: A 100 dry eye patients were enlisted and screened. Patients were allotted randomly into 2 groups-(Group-A) 2% rebamipide or (Group-B) 0.5% Carboxy methylcellulose (CMC) ophthalmic solution, after screening and instilled as 1 drop in each eye four times a day, for about two months. The signs and symptoms were assessed -at baseline, 2, 4, and at 8-week visits. The objective signs were –“Schirmer test and Tear film break-up time” (TBUT) while subjective symptoms were dry eye related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision. Results: A compelling improvement was noticed in the Schirmer test and TBUT values after the treatment in the 2% rebamipide group. The patients on 2% rebamipide eye drop showed considerable improvement in dry eye related ocular symptoms, than the patients on 0.5% CMC eye drop (51% and 29% respectively) at 2 months. Conclusions: 2% rebamipide ophthalmic solution was more efficient in improving both the subjective symptoms and objective signs of dry eye in comparison to the CMC group in this 8-week study. These findings showed that 2% rebamipide is the more effective drug for dry eye. Keywords: Carboxy methylcellulose, Dry eye, Efficacy, Rebamipide.

Hepatoprotective effect of rebamipide against methotrexate-induced hepatic intoxication: role of Nrf2/GSK-3β, NF-κβ-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2 signaling pathways

Objectives The fact that methotrexate (MTX) is hepatotoxic is an important reason to limit its clinical use. Rebamipide (REB) has antioxidant and anti-inflammatory properties and is useful for the treatment of gastro-duodenal ulcers. This study investigated the impact and protective mechanisms of REB against MTX-induced hepatotoxicity in rats. Materials and Methods Animals were divided into four groups of six rats each: a control group, REB group (REB 100 mg/kg/day, orally), MTX control group (20 mg/kg, single i.p.), and MTX + REB group. Results The administration of MTX induced marked hepatic injury in the form of hepatocyte inflammatory swelling, degeneration, apoptosis, and focal necrosis. In parallel, our biochemical investigations revealed a marked hepatic dysfunction associated with the disturbance of the oxidant/antioxidant balance in the group treated with only MTX. Moreover, MTX led to the down-regulation of the hepatic Nrf2 and Bcl-2 expressions along with a marked elevation in the hepatic NF-κβ-p65, GSK-3β, JAK1, STAT3, PUMA, and Bax expressions. On the other hand, co-treatment with REB significantly ameliorated the aforementioned histopathological, biochemical, and molecular defects caused by MTX treatment. Conclusion the outcomes of the present study showed REB’s ability to protect from hepatic injury induced by MTX, possibly through its antioxidant, anti-inflammatory, and anti-apoptotic properties. These effects could be attributed to REB’s ability to modulate, at least in part, the Nrf2/GSK-3β,NF-κβ-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2signaling pathways.

Rebamipide potentially mitigates methotrexate-induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study.

Methotrexate (MTX) is a widely used chemotherapeutic agent; nevertheless, the nephrotoxicity associated with its use has limited its clinical use. Rebamipide (REB) is a gastro-protective agent with diverse promising biological activities. Here, we investigated the renoprotective effects of REB against MTX-induced nephrotoxicity in rats. Male Wistar rats were allocated into four groups: the normal control group, the REB group (100 mg kg-1 day-1 , PO, for 12 days), the MTX group (which received a single injection of 20 mg/kg, ip), and the REB + MTX group (which received 100 mg kg-1 day-1 REB for 7 days before and 5 days after being injected with 20 mg/kg MTX). Interestingly, MTX triggered kidney injury, characterized by renal dysfunction along with histopathological alterations. Moreover, increased reactive oxygen species level and inflammatory response were detected in the kidney of MTX-treated rats. However, REB prevented MTX-induced oxidative kidney injury and boosted an antioxidant balance. Mechanistically, REB markedly activated the NRF-2 protein and upregulated the expression of both SIRT-1 and FOXO-3 genes. Additionally, REB administration strongly inhibited the inflammatory response by downregulating both NF-κB-p65 and TLR-4. Finally, the coadministration of REB and MTX activated the mTOR/PI3K/AKT signaling pathway. Simultaneously, REB treatment attenuated the reduction in glomerular size, the widening of the capsular spaces, and the tubular cell damage due to MTX administration. Taken together, these results indicate the potential of REB as adjuvant therapy to prevent nephrotoxicity in patients receiving MTX treatment.

459 The Effect of Rebamipide in Patients With Gastroesophageal Reflux Disease, Including Non-Erosive Reflux Disease: A Multi-Center, Randomized, Single-Blind, Placebo-Controlled Study (RENERD Study)

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a chronic and frequently relapsing disease. The etiology of non-erosive reflux disease (NERD) remains unclear, but it has been reported to manifest histologic changes such as dilated intercellular spaces (DIS) and inflammatory cells infiltration in the esophageal mucosa. In this study, we investigated the effect of rebamipide, a mucosal protective agent, in the recurrence of symptoms in GERD patients during proton pump inhibitor (PPI) and also examined histologic changes in the esophageal mucosa of NERD patients. METHODS: A total of 139 patients with GERD including 50 patients with NERD were enrolled in this study and were treated randomly with either PPI plus rebamipide (rebamipide group) or PPI plus placebo (placebo group) during 8 weeks. We compared the change of symptom score at 8 weeks in both groups using a GERD questionnaire. In addition, we analyzed histologic findings such as DIS, inflammatory cells infiltration, and basal cell hyperplasia in the esophageal mucosa of NERD patients, and we compared the histologic changes at 8 weeks in both groups. RESULTS: After 8 weeks, the mean decreases in the total symptom score in the rebamipide group were greater than those in the placebo group in GERD patients, but not statistically significant (-4.4 ± 2.7 vs. -3.9 ± 3.1, P = 0.382). However, the proportion of at least a 50% decrease in the total symptom score in the rebamipide group was significantly higher than that in the placebo group (74.1% vs. 51.7%, P = 0.020). With regard to histologic changes in NERD patients, the severity of DIS in the rebamipide group was significantly improved compared to that in the placebo group after 8 weeks (P = 0.024), and also the lymphocytes counts were more decreased in the rebamipide group compared to the placebo group (P = 0.026). CONCLUSION: Rebamipide, a mucosal protective agent, might be helpful in attenuating the recurrence of symptoms in GERD patients. It could also improve histologic abnormalities in the esophageal mucosa of NERD patients.

The Effects of Rebamipide 2% Ophthalmic Solution Application on Murine Subbasal Corneal Nerves After Environmental Dry Eye Stress

Rebamipide ophthalmic solution is a mucin secretagogue which is an important therapeutic agent in the treatment of dry eye. It has been noted that dry eye in office workers is associated with a decrease in secretory mucin. This study aimed to evaluate the effects of 2% rebamipide ophthalmic solution in mice subjected to environmental dry eye stress (EDES), which mimics the conditions of office workers. Thirty eyes from thirty BALB/c mice (eight-week-old males) were divided into three treatment groups: artificial tear (vehicle), 2% rebamipide ophthalmic solution, and 0.1% hyaluronic acid (HA) ophthalmic solution. After four days of pretreatment, mice were exposed to EDES for three days. The corneal subbasal nerve and inflammatory cells were then examined using in vivo confocal microscopy. Following EDES exposure, the lissamine green staining score was significantly lower and corneal sensitivity was more preserved in the 2% rebamipide group than in the HA group. In addition, the subbasal nerve fiber density was significantly higher and the DC density was significantly lower in the 2% rebamipide group than in the HA group. Overall, the topical rebamipide ophthalmic solution showed more favorable therapeutic effects when compared to the HA ophthalmic solution in a mouse model of EDES, likely owing to its anti-inflammatory and neuroprotective effects.

The effectiveness of rebamipide mouthwash therapy for radiotherapy and chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis

BackgroundOral mucositis is a frequent and severe adverse event in patients undergoing chemoradiotherapy for head and neck cancers, especially grade 3 or 4 mucositis. Occurrence may result in drop-out from treatment, thereby reducing survival. We aimed to clarify the effectiveness and safety of rebamipide mouthwash for oral mucositis in patients with head and neck cancer receiving treatment.MethodsWe carried out a systematic review and meta-analysis of patients with head and neck cancer who were treated with rebamipide mouthwash. We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), and the World Health Organization (WHO) International Clinical Trial Registry Platform. The primary outcome was the incidence of severe oral mucositis, and secondary outcomes were time from treatment start to onset of oral mucositis, the response rate of radiotherapy, and any adverse events.ResultsWe included three studies comparing rebamipide versus placebo, all of which evaluating chemoradiotherapy induced oral mucositis. The chemotherapeutic agent was docetaxel in one study and cisplatin in the remaining two. Radiotherapy in each study consisted of 3D-conformal radiation therapy, intensity modulated radiation therapy and conventional radiation therapy, respectively. The calculated odds ratio was 0.29 [95% confidence interval (CI): 0.15 to 0.55], showing a positive association in the three studies between the incidence of grade 3–4 oral mucositis and chemotherapy for head and neck cancer. One study reported an onset of oral mucositis and the time to onset was 14.6 ± 6.4 days for the rebamipide group and 11.2 ± 4.4 days for placebo. One study reported a complete response of 8.3% for placebo and 16.7% for the rebamipide the group, and the partial response was 91.7 and 75.0%, respectively. Adverse events were reported in two studies to be 6.1 and 11.6% for placebo, and 19.4 and 26.0% in the rebamipide group, respectively.ConclusionsRebamipide mouthwash is effective in the prevention of severe mucositis and stomatitis. However, evaluation of adverse events in observational studies are needed.

Cytoprotective agent for peptic ulcer prevention in patients taking dual antiplatelet agents: A randomized, double-blind placebo-controlled trial.

Long-term use of dual antiplatelets is increasing, and most patients need primary peptic ulcer prophylaxis. The long-term use of proton pump inhibitors (PPIs) is associated with adverse events. We evaluated the efficacy of rebamipide for peptic ulcer prevention. This randomized controlled trial was conducted between July 2014 and November 2017. Patients receiving dual antiplatelets for ≥1year with no history of peptic ulcer bleeding or perforation were recruited and randomly assigned to the rebamipide (300mg/day) group or the placebo group. Patients who used proton pump inhibitors were excluded. The primary endpoint was a new mucosal break on esophagogastroduodenoscopy at 3 or 12months after treatment initiation. The secondary endpoints were hematocrit changes from the baseline, gastrointestinal bleeding, and chest pain. Antiplatelet function was assessed. In total, 95 eligible patients were identified; 12 were excluded, and 83 patients were randomized, with 66 (79.5%) and 59 (71.1%) patients eligible at the 3- and 12-month follow ups, respectively. The baseline characteristics were equivalent between the groups. During the 12months of follow up, 13 patients (43.3%) taking rebamipide and 19 (65.5%) taking the placebo experienced mucosal injury (P=0.07). Two patients (6.7%) taking rebamipide and eight (27.6%) taking the placebo had peptic ulcers ≥5mm or <5mm with pigmented spots (P=0.03). The changes in hematocrit were not different between the two groups. Neither bleeding ulcers nor chest pain was observed. Rebamipide is safe and may prevent peptic ulcers ≥5mm in diameter or those with pigmented spots in patients receiving dual antiplatelets for 1year (NCT02166008).