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Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis

Busulfan is used as a chemotherapeutic drug to treat childhood and adult chronic myelogenous leukemia, and as an immunosuppressive agent before bone marrow transplantation. A key side effect of busulfan is the alteration of male reproductive function. Infertility caused by anti-cancer treatments has...

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Autores principales: Qu, Ning, Kuramasu, Miyuki, Nagahori, Kenta, Ogawa, Yuki, Hayashi, Shogo, Hirayanagi, Yoshie, Terayama, Hayato, Suyama, Kaori, Sakabe, Kou, Itoh, Masahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084192/
https://www.ncbi.nlm.nih.gov/pubmed/32138301
http://dx.doi.org/10.3390/ijms21051716
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author Qu, Ning
Kuramasu, Miyuki
Nagahori, Kenta
Ogawa, Yuki
Hayashi, Shogo
Hirayanagi, Yoshie
Terayama, Hayato
Suyama, Kaori
Sakabe, Kou
Itoh, Masahiro
author_facet Qu, Ning
Kuramasu, Miyuki
Nagahori, Kenta
Ogawa, Yuki
Hayashi, Shogo
Hirayanagi, Yoshie
Terayama, Hayato
Suyama, Kaori
Sakabe, Kou
Itoh, Masahiro
author_sort Qu, Ning
collection PubMed
description Busulfan is used as a chemotherapeutic drug to treat childhood and adult chronic myelogenous leukemia, and as an immunosuppressive agent before bone marrow transplantation. A key side effect of busulfan is the alteration of male reproductive function. Infertility caused by anti-cancer treatments has become a significant concern, but there are currently limited treatments for this condition. Recently, we demonstrated that Gosha-jinki-gan, a traditional Japanese medicine, completely reversed the spermatogenesis defects caused by cancer treatment in mice. Hochu-ekki-to and Hachimi-jio-gan are commonly used to treat male infertility, and Hachimi-jio-gan shares herbal ingredients with Gosha-jinki-gan. Therefore, in the present study, we administered Hachimi-jio-gan and Hochu-ekki-to alone or in combination to mice with severe aspermatogenesis caused by busulfan treatment. We performed testis weight measurements, quantitative histological assessments of the testes and the epididymis, and evaluated sperm counts and morphology. We also assessed the expression of immune mediators and macrophage markers. Treatment with a combination of both the medicines significantly reduced busulfan-induced testicular toxicity when compared to the lone treatment with either medicine. We demonstrated that treatment efficacy was related to a differential impact on testicular inflammation, and that the synergistic effect of co-administration completely reversed the busulfan-induced damage to the reproductive functions.
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spelling pubmed-70841922020-03-24 Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis Qu, Ning Kuramasu, Miyuki Nagahori, Kenta Ogawa, Yuki Hayashi, Shogo Hirayanagi, Yoshie Terayama, Hayato Suyama, Kaori Sakabe, Kou Itoh, Masahiro Int J Mol Sci Article Busulfan is used as a chemotherapeutic drug to treat childhood and adult chronic myelogenous leukemia, and as an immunosuppressive agent before bone marrow transplantation. A key side effect of busulfan is the alteration of male reproductive function. Infertility caused by anti-cancer treatments has become a significant concern, but there are currently limited treatments for this condition. Recently, we demonstrated that Gosha-jinki-gan, a traditional Japanese medicine, completely reversed the spermatogenesis defects caused by cancer treatment in mice. Hochu-ekki-to and Hachimi-jio-gan are commonly used to treat male infertility, and Hachimi-jio-gan shares herbal ingredients with Gosha-jinki-gan. Therefore, in the present study, we administered Hachimi-jio-gan and Hochu-ekki-to alone or in combination to mice with severe aspermatogenesis caused by busulfan treatment. We performed testis weight measurements, quantitative histological assessments of the testes and the epididymis, and evaluated sperm counts and morphology. We also assessed the expression of immune mediators and macrophage markers. Treatment with a combination of both the medicines significantly reduced busulfan-induced testicular toxicity when compared to the lone treatment with either medicine. We demonstrated that treatment efficacy was related to a differential impact on testicular inflammation, and that the synergistic effect of co-administration completely reversed the busulfan-induced damage to the reproductive functions. MDPI 2020-03-03 /pmc/articles/PMC7084192/ /pubmed/32138301 http://dx.doi.org/10.3390/ijms21051716 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Qu, Ning
Kuramasu, Miyuki
Nagahori, Kenta
Ogawa, Yuki
Hayashi, Shogo
Hirayanagi, Yoshie
Terayama, Hayato
Suyama, Kaori
Sakabe, Kou
Itoh, Masahiro
Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis
title Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis
title_full Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis
title_fullStr Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis
title_full_unstemmed Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis
title_short Co-Administration of the Traditional Medicines Hachimi-Jio-Gan and Hochu-Ekki-To Can Reverse Busulfan-Induced Aspermatogenesis
title_sort co-administration of the traditional medicines hachimi-jio-gan and hochu-ekki-to can reverse busulfan-induced aspermatogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084192/
https://www.ncbi.nlm.nih.gov/pubmed/32138301
http://dx.doi.org/10.3390/ijms21051716
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