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Pravastatin reduces radiation-induced damage in normal tissues

Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice...

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Autores principales: Doi, Hiroshi, Matsumoto, Seiji, Odawara, Soichi, Shikata, Toshiyuki, Kitajima, Kazuhiro, Tanooka, Masao, Takada, Yasuhiro, Tsujimura, Tohru, Kamikonya, Norihiko, Hirota, Shozo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443166/
https://www.ncbi.nlm.nih.gov/pubmed/28565765
http://dx.doi.org/10.3892/etm.2017.4192
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author Doi, Hiroshi
Matsumoto, Seiji
Odawara, Soichi
Shikata, Toshiyuki
Kitajima, Kazuhiro
Tanooka, Masao
Takada, Yasuhiro
Tsujimura, Tohru
Kamikonya, Norihiko
Hirota, Shozo
author_facet Doi, Hiroshi
Matsumoto, Seiji
Odawara, Soichi
Shikata, Toshiyuki
Kitajima, Kazuhiro
Tanooka, Masao
Takada, Yasuhiro
Tsujimura, Tohru
Kamikonya, Norihiko
Hirota, Shozo
author_sort Doi, Hiroshi
collection PubMed
description Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy.
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spelling pubmed-54431662017-05-30 Pravastatin reduces radiation-induced damage in normal tissues Doi, Hiroshi Matsumoto, Seiji Odawara, Soichi Shikata, Toshiyuki Kitajima, Kazuhiro Tanooka, Masao Takada, Yasuhiro Tsujimura, Tohru Kamikonya, Norihiko Hirota, Shozo Exp Ther Med Articles Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy. D.A. Spandidos 2017-05 2017-03-08 /pmc/articles/PMC5443166/ /pubmed/28565765 http://dx.doi.org/10.3892/etm.2017.4192 Text en Copyright: © Doi et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Doi, Hiroshi
Matsumoto, Seiji
Odawara, Soichi
Shikata, Toshiyuki
Kitajima, Kazuhiro
Tanooka, Masao
Takada, Yasuhiro
Tsujimura, Tohru
Kamikonya, Norihiko
Hirota, Shozo
Pravastatin reduces radiation-induced damage in normal tissues
title Pravastatin reduces radiation-induced damage in normal tissues
title_full Pravastatin reduces radiation-induced damage in normal tissues
title_fullStr Pravastatin reduces radiation-induced damage in normal tissues
title_full_unstemmed Pravastatin reduces radiation-induced damage in normal tissues
title_short Pravastatin reduces radiation-induced damage in normal tissues
title_sort pravastatin reduces radiation-induced damage in normal tissues
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443166/
https://www.ncbi.nlm.nih.gov/pubmed/28565765
http://dx.doi.org/10.3892/etm.2017.4192
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