Rebamipide Increases Mucin-Like Substance Contents and Periodic Acid Schiff Reagent-Positive Cells Density in Normal Rabbits

Urashima, Hiroki; Takeji, Yasuhiro; Okamoto, Takashi; Fujisawa, Shigeki; Shinohara, Hisashi

doi:10.1089/jop.2011.0147

Cited by 57 publications

(37 citation statements)

References 20 publications

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“…17 It is known that the application of topical rebamipide increases both the number of goblet cells and the level of mucin-like substances in the bulbar conjunctiva of rabbits, 18,19 promotes the proliferation of cultured rat conjunctival goblet cells, 20 and induces the mucin secretion from cultured conjunctival goblet cells of rats. 21 Application of rebamipide alleviates the inflammation in the small intestine through its anti-inflammatory effects and activation of the Wnt/β-catenin pathway.…”

Section: Introductionmentioning

confidence: 99%

Rebamipide alleviates radiation‐induced colitis through improvement of goblet cell differentiation in mice

Jang

Park

Lee

et al. 2018

J of Gastro and Hepatol

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Background and Aim: Radiation-induced colitis is a common clinical problem associated with radiotherapy and accidental exposure to ionizing radiation. Goblet cells play a pivotal role in the intestinal barrier against pathogenic bacteria. Rebamipide, an anti-gastric ulcer drug, has the effects to promote goblet cell proliferation. The aim of this study was to investigate whether radiation-induced colonic injury could be alleviated by rebamipide. Methods: This study orally administered rebamipide for 6 days to mice, which were subjected to 13 Gy abdominal irradiation, to evaluate the therapeutic effects of rebamipide against radiation-induced colitis. To confirm the effects of rebamipide on irradiated colonic epithelial cells, this study used the HT29 cell line. Results: Rebamipide clearly alleviated the acute radiation-induced colitis, as reflected by the histopathological data, and significantly increased the number of goblet cells. The drug also inhibited intestinal inflammation and protected from bacterial translocation during acute radiation-induced colitis. Furthermore, rebamipide significantly increased mucin 2 expression in both the irradiated mouse colon and human colonic epithelial cells. Additionally, rebamipide accelerated not only the recovery of defective tight junctions but also the differentiation of impaired goblet cells in an irradiated colonic epithelium, which indicates that rebamipide has beneficial effects on the colon. Conclusions: Rebamipide is a therapeutic candidate for radiation-induced colitis, owing to its ability to inhibit inflammation and protect the colonic epithelial barrier.

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Section: Introductionmentioning

confidence: 99%

Rebamipide alleviates radiation‐induced colitis through improvement of goblet cell differentiation in mice

Jang

Park

Lee

et al. 2018

J of Gastro and Hepatol

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“…Otherwise, the increases in the action of conjunctival mucin for both ultrafine (Fig. 8) and microparticle 6) suspensions might have reached the maximal effect with rebamipide concentrations of 2% or less in the rabbits that were tested for the present study.…”

Section: Discussionmentioning

confidence: 89%

“…1,2) In the ophthalmologic field, a 2% rebamipide ophthalmic suspension (Mucosta ® ophthalmic suspension UD2%) is known to be effective for the treatment of dry eyes, 3,4) and, therefore, has been marketed in Japan for the treatment of this condition since January 2012. Rebamipide increases the mucin-like glycoproteins 5,6) and suppresses cytokine production in the cornea and conjunctiva, 7,8) which results in improvements in symptoms related to dry eyes.…”

mentioning

confidence: 99%

Preparation of an Ultrafine Rebamipide Ophthalmic Suspension with High Transparency

Matsuda

Hiraoka

Urashima

et al. 2017

Biological & Pharmaceutical Bulletin

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A 2% commercially available, milky-white, rebamipide micro-particle suspension is used to treat dry eyes, and it causes short-term blurring of the patient's vision. In the current study, to improve the transparency of a rebamipide suspension, we attempted to obtain a clear rebamipide suspension by transforming the rebamipide particles to an ultrafine state. In the initial few efforts, various rebamipide suspensions were prepared using a neutralizing crystallization method with additives, but the suspensions retained their opaque quality. However, as a consequence of several critical improvements in the neutralizing crystallization methods such as selection of additives for crystallization, process parameters during crystallization, the dispersion method, and dialysis, we obtained an ultrafine rebamipide suspension (2%) that was highly transparent (transmittance at 640 nm: 59%). The particle size and transparency demonstrated the fewest level of changes at 25°C after 3 years, compared to initial levels. During that period, no obvious particle sedimentation was observed. The administration of this ultrafine rebamipide suspension (2%) increased the conjunctival mucin, which was comparable to the commercially available micro-particle suspension (2%). The corneal and conjunctival concentration of rebamipide following ocular administration of the ultrafine suspension was slightly higher than that of the micro-particle suspension. The ultrafine rebamipide suspension (eye-drop formulation) with a highly transparent ophthalmic clearness should improve a patient's QOL by preventing even a shortened period of blurred vision.

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“…Now marketed in Japan, however, are diquafosol ophthalmic solution (Diquas Ophthalmic Solution 3%; Santen Pharmaceutical Co., Ltd., Osaka, Japan) and rebamipide ophthalmic solution (Mucosta ophthalmic suspension UD2%; Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan). Both ophthalmic solutions induce mucin production 2,3 .…”

Section: Introductionmentioning

confidence: 99%

“…Rebamipide also exerts further effects on the ocular surface cells. Experiments have shown that rebamipide increases the amount of mucinlike substances in the conjunctival goblet cells and in keratoconjunctival epithelial cells in vitro and in vivo 2,6,7 . In addition, as a clinical topical agent rebamipide has been shown to increase the number of mucin-containing goblet cells 8 .…”

Section: Introductionmentioning

confidence: 99%

Improvements in Signs and Symptoms of Dry Eye after Instillation of 2% Rebamipide

et al. 2015

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Purpose: Because dry eye greatly reduces quality of life, this study aimed to examine rebamipide instillation in patients with dry eye and assess the improvement of signs and symptoms as evaluated with the Ocular Surface Disease Index, which is the most popular index and is highly reliable. Methods:From June 2013 through January 2014, we examined 50 eyes of 25 patients with dry eye (6 men and 19 woman) at our institution. Dry eye was diagnosed on the basis of the presence of symptoms, tear dynamics, and ocular surface abnormalities according to the Japanese criteria for dry eye. Before being enrolled, all patients underwent ocular surface health assessment, including history interviews, and completed the Ocular Surface Disease Index questionnaire. Patients received 2% rebamipide ophthalmic solution 4 times daily for 4 weeks. Signs and symptoms were analyzed before and 4 weeks after rebamipide administration. Tear dynamics, tear break-up time, and ocular surface abnormalities were measured and compared between before and 4 weeks after rebamipide administration. Results:Of the 25 patients, 9 had definite dry eye and 16 had probable dry eye. Tear break-up time and the fluorescein staining score significantly improved after 4 weeks. However, no significant change was observed for the Schirmer test I and the lissamine green staining score. Conclusions:The administration of 2% rebamipide 4 times daily for 4 weeks improves the signs and symptoms of dry eye and improves patients' quality of life. (J Nippon Med Sch 2015; 82: 229 236)

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Rebamipide Increases Mucin-Like Substance Contents and Periodic Acid Schiff Reagent-Positive Cells Density in Normal Rabbits

Abstract: Rebamipide is a possible candidate drug for treatment of cornea and conjunctival epithelial damage due to its mucin-like substance increasing action, for instance, in the treatment of dry eye disease.

Cited by 57 publications

References 20 publications

Rebamipide alleviates radiation‐induced colitis through improvement of goblet cell differentiation in mice

Rebamipide alleviates radiation‐induced colitis through improvement of goblet cell differentiation in mice

Preparation of an Ultrafine Rebamipide Ophthalmic Suspension with High Transparency

Improvements in Signs and Symptoms of Dry Eye after Instillation of 2% Rebamipide

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