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Title: Rebamipide ameliorates radiation-induced intestinal injury in a mouse model

Abstract

Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13 Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased. The intestinal damage reached a maximum level on day 6 post-IR and intestinal regeneration occurred thereafter. We found that rebamipide significantly ameliorated radiation-induced intestinal injury. In mice treated with rebamipide after IR, intestinal barrier function recovered and expression of the tight junction components of the intestinal barrier were upregulated. Rebamipide administration reduced radiation-induced intestinal mucosal injury. The levels of proinflammatory cytokines and matrix metallopeptidase 9 (MMP9) were significantly reduced upon rebamipide administration. Intestinal cell proliferation and β-catenin expression also increased upon rebamipide administration. These data demonstrate that rebamipide reverses impairment of the intestinal barrier by increasing intestinal cell proliferation and attenuating the inflammatory response by inhibiting MMP9 and proinflammatory cytokine expression inmore » a murine model of radiation-induced enteritis. - Highlights: • The first study on the therapeutic effects of rebamipide in radiation injury. • Irradiation destructed microscopic structures and intestinal barrier. • Rebamipide recovered intestinal barrier function and tight junction components. • Rebamipide reduced the levels of pro-inflammatory cytokines and MMP 9. • Intestinal cell proliferation and β-catenin expression increased by rebamipide.« less

Authors:
; ;  [1];  [1];  [2]; ; ; ; ; ;  [1];  [1];  [2];  [1];  [2]
  1. Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)
  2. (Korea, Republic of)
Publication Date:
OSTI Identifier:
22722887
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 329; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; DIFFUSION BARRIERS; INTESTINES; LYMPHOKINES; MICE; RADIATION INJURIES; SIDE EFFECTS; VENTILATION BARRIERS

Citation Formats

Shim, Sehwan, Jang, Hyo-Sun, Myung, Hyun-Wook, Myung, Jae Kyung, Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Kang, Jin-Kyu, Kim, Min-Jung, Lee, Seung Bum, Jang, Won-Suk, Lee, Sun-Joo, Jin, Young-Woo, Lee, Seung-Sook, Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Park, Sunhoo, and Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul. Rebamipide ameliorates radiation-induced intestinal injury in a mouse model. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.05.012.
Shim, Sehwan, Jang, Hyo-Sun, Myung, Hyun-Wook, Myung, Jae Kyung, Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Kang, Jin-Kyu, Kim, Min-Jung, Lee, Seung Bum, Jang, Won-Suk, Lee, Sun-Joo, Jin, Young-Woo, Lee, Seung-Sook, Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Park, Sunhoo, & Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul. Rebamipide ameliorates radiation-induced intestinal injury in a mouse model. United States. doi:10.1016/J.TAAP.2017.05.012.
Shim, Sehwan, Jang, Hyo-Sun, Myung, Hyun-Wook, Myung, Jae Kyung, Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Kang, Jin-Kyu, Kim, Min-Jung, Lee, Seung Bum, Jang, Won-Suk, Lee, Sun-Joo, Jin, Young-Woo, Lee, Seung-Sook, Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Park, Sunhoo, and Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul. Tue . "Rebamipide ameliorates radiation-induced intestinal injury in a mouse model". United States. doi:10.1016/J.TAAP.2017.05.012.
@article{osti_22722887,
title = {Rebamipide ameliorates radiation-induced intestinal injury in a mouse model},
author = {Shim, Sehwan and Jang, Hyo-Sun and Myung, Hyun-Wook and Myung, Jae Kyung and Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul and Kang, Jin-Kyu and Kim, Min-Jung and Lee, Seung Bum and Jang, Won-Suk and Lee, Sun-Joo and Jin, Young-Woo and Lee, Seung-Sook and Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul and Park, Sunhoo and Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul},
abstractNote = {Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13 Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased. The intestinal damage reached a maximum level on day 6 post-IR and intestinal regeneration occurred thereafter. We found that rebamipide significantly ameliorated radiation-induced intestinal injury. In mice treated with rebamipide after IR, intestinal barrier function recovered and expression of the tight junction components of the intestinal barrier were upregulated. Rebamipide administration reduced radiation-induced intestinal mucosal injury. The levels of proinflammatory cytokines and matrix metallopeptidase 9 (MMP9) were significantly reduced upon rebamipide administration. Intestinal cell proliferation and β-catenin expression also increased upon rebamipide administration. These data demonstrate that rebamipide reverses impairment of the intestinal barrier by increasing intestinal cell proliferation and attenuating the inflammatory response by inhibiting MMP9 and proinflammatory cytokine expression in a murine model of radiation-induced enteritis. - Highlights: • The first study on the therapeutic effects of rebamipide in radiation injury. • Irradiation destructed microscopic structures and intestinal barrier. • Rebamipide recovered intestinal barrier function and tight junction components. • Rebamipide reduced the levels of pro-inflammatory cytokines and MMP 9. • Intestinal cell proliferation and β-catenin expression increased by rebamipide.},
doi = {10.1016/J.TAAP.2017.05.012},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 329,
place = {United States},
year = {2017},
month = {8}
}