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A study of the effect of sequential injection of 5-androstenediol on irradiation-induced myelosuppression in mice

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Abstract

Herein, we aimed at examining the therapeutic effects of 5-androstenediol (5-AED), a natural hormone produced in the adrenal cortex, on radiation-induced myelosuppression in C3H/HeN mice. The mice were subjected to whole-body irradiation with a sublethal dose of 5 Gy gamma-irradiation to induce severe myelosuppression, and 5-AED (50 mg/kg) was administered subcutaneously. 5-AED was administrated 1 day before irradiation (pre-treatment) or twice weekly for 3 weeks starting from 1 h after irradiation (post-treatment). Treatment with 5-AED significantly ameliorated the decrease in the peripheral blood neutrophil and platelet populations in irradiated myelosuppressive mice, but had no effect on the lymphocyte population. It also ameliorated hypocellularity and disruption of bone marrow induced by irradiation and led to rapid recovery of myeloid cells. Further, it attenuated the decrease in spleen weight and megakaryocyte and myeloid cell populations in the spleen and promoted multilineage hematopoietic recovery. We found that a single injection of 5-AED produced only a temporary therapeutic effect, while sequential injection of 5-AED after irradiation had a more pronounced and prolonged therapeutic effect and reduced myelosuppression by irradiation. Thus, sequential injection of 5-AED after irradiation has therapeutic potential for radiation-induced myelosuppression when administered continuously and can be a significant therapeutic candidate for the management of acute radiation syndrome, particularly in a mass casualty scenario where rapid and economic intervention is important.

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Acknowledgments

This study was supported by the project titled ‘Development of therapeutic improvement on acute radiation syndrome (50581-2013)’ of Ministry of Science, ICT and Future Planning (MSIP), Korean government.

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Authors and Affiliations

  1. Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), 267-2 Jwadong-gil, Jangan-eup, Busan, 619-953, Korea

    Joong Sun Kim & Yeonghoon Son

  2. Laboratory of Radiation Exposure & Therapeutics, Korea Institute of Radiological & Medical Sciences (KIRAMS), 215-4 Gongneung-dong Nowon-ku, Seoul, 139-706, Korea

    Joong Sun Kim, Won Suk Jang, Sunjoo Lee, Sunhoo Park & Seung Sook Lee

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  1. Joong Sun Kim
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  2. Won Suk Jang
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Correspondence to Joong Sun Kim or Seung Sook Lee.

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Kim, J.S., Jang, W.S., Lee, S. et al. A study of the effect of sequential injection of 5-androstenediol on irradiation-induced myelosuppression in mice. Arch. Pharm. Res. 38, 1213–1222 (2015). https://doi.org/10.1007/s12272-014-0483-5

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  • DOI: https://doi.org/10.1007/s12272-014-0483-5

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