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The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation

For the primary treatment of emergency exposure to high-dose radiation, such as in the event of a radiation accident, the top priority is the reconstitution and restoration of haematopoiesis. In most radiation accidents, drug therapy is chosen as the most suitable treatment; the chosen drug should a...

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Autores principales: Yamaguchi, Masaru, Hirouchi, Tokuhisa, Yokoyama, Koki, Nishiyama, Ayaka, Murakami, Sho, Kashiwakura, Ikuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045643/
https://www.ncbi.nlm.nih.gov/pubmed/30006622
http://dx.doi.org/10.1038/s41598-018-29013-5
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author Yamaguchi, Masaru
Hirouchi, Tokuhisa
Yokoyama, Koki
Nishiyama, Ayaka
Murakami, Sho
Kashiwakura, Ikuo
author_facet Yamaguchi, Masaru
Hirouchi, Tokuhisa
Yokoyama, Koki
Nishiyama, Ayaka
Murakami, Sho
Kashiwakura, Ikuo
author_sort Yamaguchi, Masaru
collection PubMed
description For the primary treatment of emergency exposure to high-dose radiation, such as in the event of a radiation accident, the top priority is the reconstitution and restoration of haematopoiesis. In most radiation accidents, drug therapy is chosen as the most suitable treatment; the chosen drug should already be approved domestically, stably supplied and regularly stockpiled. In the present study, a single administration of romiplostim (RP), an approved thrombopoietin receptor agonist, produced a 100% survival rate in C57BL/6 J mice exposed to a lethal dose (7 Gy) of (137)Cs γ-rays, and all irradiated mice survived for more than 30 days with both 3- and 5-day consecutive administrations. By day 30, the peripheral blood cells, bone marrow cells and haematopoietic progenitor cells of the RP-administered irradiated mice had all recovered to a level that was not significantly different from that in non-irradiated mice. In contrast to myelosuppression, which did not fully recover until day 30, the expression of several bone marrow cell surface antigens recovered sooner, and DNA repair concurrently increased in haematopoietic cells, speeding the resolution of double strand breaks and reducing the rates of apoptosis. These findings suggest that RP may be a clinic-ready countermeasure to treat victims of radiation accidents.
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spelling pubmed-60456432018-07-16 The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation Yamaguchi, Masaru Hirouchi, Tokuhisa Yokoyama, Koki Nishiyama, Ayaka Murakami, Sho Kashiwakura, Ikuo Sci Rep Article For the primary treatment of emergency exposure to high-dose radiation, such as in the event of a radiation accident, the top priority is the reconstitution and restoration of haematopoiesis. In most radiation accidents, drug therapy is chosen as the most suitable treatment; the chosen drug should already be approved domestically, stably supplied and regularly stockpiled. In the present study, a single administration of romiplostim (RP), an approved thrombopoietin receptor agonist, produced a 100% survival rate in C57BL/6 J mice exposed to a lethal dose (7 Gy) of (137)Cs γ-rays, and all irradiated mice survived for more than 30 days with both 3- and 5-day consecutive administrations. By day 30, the peripheral blood cells, bone marrow cells and haematopoietic progenitor cells of the RP-administered irradiated mice had all recovered to a level that was not significantly different from that in non-irradiated mice. In contrast to myelosuppression, which did not fully recover until day 30, the expression of several bone marrow cell surface antigens recovered sooner, and DNA repair concurrently increased in haematopoietic cells, speeding the resolution of double strand breaks and reducing the rates of apoptosis. These findings suggest that RP may be a clinic-ready countermeasure to treat victims of radiation accidents. Nature Publishing Group UK 2018-07-13 /pmc/articles/PMC6045643/ /pubmed/30006622 http://dx.doi.org/10.1038/s41598-018-29013-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yamaguchi, Masaru
Hirouchi, Tokuhisa
Yokoyama, Koki
Nishiyama, Ayaka
Murakami, Sho
Kashiwakura, Ikuo
The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation
title The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation
title_full The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation
title_fullStr The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation
title_full_unstemmed The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation
title_short The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation
title_sort thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045643/
https://www.ncbi.nlm.nih.gov/pubmed/30006622
http://dx.doi.org/10.1038/s41598-018-29013-5
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