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

Abstract
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.
AuthorsNing Qu, Miyuki Kuramasu, Kenta Nagahori, Yuki Ogawa, Shogo Hayashi, Yoshie Hirayanagi, Hayato Terayama, Kaori Suyama, Kou Sakabe, Masahiro Itoh
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 5 (Mar 03 2020) ISSN: 1422-0067 [Electronic] Switzerland
PMID32138301 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents, Alkylating
  • Drugs, Chinese Herbal
  • bu-zhong-yi-qi-tang
  • hachimijiogan
  • Busulfan
Topics
  • Animals
  • Antineoplastic Agents, Alkylating (adverse effects)
  • Apoptosis (drug effects)
  • Body Weight (drug effects)
  • Busulfan (adverse effects)
  • Cell Proliferation (drug effects)
  • Disease Models, Animal
  • Drugs, Chinese Herbal (therapeutic use)
  • Male
  • Medicine, East Asian Traditional
  • Medicine, Traditional (methods)
  • Mice
  • Sperm Count
  • Spermatogenesis (drug effects)
  • Spermatozoa (drug effects)
  • Testis (drug effects, metabolism)

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