Abstract 4430: Protective effects of rebamipide liquid on radiation-induced glositis in rats.

Abstract

[Background & Aims] Rebamipide is widely used for mucosal protection, healing of gastric ulcers and treatment of gastritis. Recently, it was reported that Rebamipide gargle inhibited oral mucositis induced by chemoradiotherapy in head and neck cancer patients. In this study, we examined protective effects of Rebamipide Liquid on radiation-induced glossitis rat model and analyzed the expression level of pro-inflammatory cytokines and chemokines in the injury area of tongue. [Materials & Methods] Rebamipide Liquid, comprising with Rebamipide crystals less than 500 nm particles, was prepared by a neutralizing crystallization technique. This formulation is a stable homogenous aqueous suspension provided with appropriate viscosity by adding viscosity enhanced agents to improve the retention in the oral cavity. The glossitis was induced by X-ray with 15Gy irradiation only around the snout (Day 0) in rats. Rebamipide Liquid was administered intraorally at doses of 5, 10 or 20 mg/kg (1, 2 or 4%, respectively), 6 times a day for 14 days from Day -7 to Day 6. These tongue tissue specimens were obtained at Day 7 and their images were recorded by a digital camera for efficacy evaluations. Gene expression analysis was performed with quantitative real-time PCR (ABI) and protein level was evaluated with Bio-Plex system(BioRad) or ELISA in a different study which was conducted at the two doses of 0 and 20 mg/kg (0 and 4%). [Result & Conclusions] The ulcer-like areas (10.8 ± 1.2, 7.9 ± 1.1 and 7.0 ± 0.7%) at doses of 5 - 20 mg/kg (1 - 4%) of Rebamipide Liquid administration, were statistically smaller than the vehicle control at 14.7±1.6%. Another study revealed that the expression of pro-inflammatory cytokines (TNF-α, IL-6 and Il-1β) and chemokines (MCP-1 and Gro-α) were dramatically elevated in the irradiated tongue at Day7, as compared to normal. But these elevated expressions were significantly suppressed by the 4% Rebamipide treatment. These immuoassays elucidated that the production of these cytokines and chemokines were significantly suppressed by the Rebamipide administration. These results demonstrated that the Rebamipide Liquid has a potent pharmacological action for the radiation-induced oral mucositis mediated by the suppression of pro-inflammatory cytokines (TNF-α, IL-6 and Il-1β) and chemokines (MCP-1 and Gro-α). Citation Format: Takako Nakashima, Naoya Uematsu, Masafumi Shibamori, Kazushi Sakurai, Masayuki Sato, Takakuni Matsuda, Nobutomo Sako. Protective effects of rebamipide liquid on radiation-induced glositis in rats. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4430. doi:10.1158/1538-7445.AM2013-4430