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Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice

  • Authors:
    • Hong Yang
    • Fei Huang
    • Yulong Tao
    • Xinbin Zhao
    • Lina Liao
    • Xia Tao
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, School of Pharmaceutical Sciences Medicine, Tsinghua University, Beijing 100084, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 762-770
    |
    Published online on: July 3, 2017
       https://doi.org/10.3892/ijmm.2017.3047
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Abstract

Simvastatin is a HMG-CoA reductase inhibitor widely used to lower plasma cholesterol and to protect against cardiovascular risk factors. The aim of this study was to investigate whether simvastatin attenuates ionizing radiation-induced damage in the mouse thymus and to elucidate the possible mechanisms invovled. For this purpose, male C57BL/6J mice aged 6 weeks were used and exposed to 4 Gy 60Co γ-radiation with or without simvastatin (20 mg/kg/day, for 14 days). Apoptosis was determined by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay or transmission electron microscopy (TEM) examination. Thymocytes were also isolated and incubated in DMEM supplemented with 10% FBS at 37˚C and exposed to 8 Gy 60Co γ-radiation with or without simvastatin (20 µM). The expression levels of Bcl-2, p53, p-p53, AKT, sirtuin 1 and poly(ADP-ribose) polymerase (PARP) were determined by western blot analysis. TUNEL and TEM examination revealed that simvastatin treatment significantly mitigated ionizing radiation-induced apoptosis in the mouse thymus. It was also found that simvastatin treatment increased AKT/sirtuin 1 expression following exposure to ionizing radiation in vivo and in vitro. In the in vivo model, but not in the in vitro model, Bcl-2 and PARP expression was augmented and that of p53/p-p53 decreased following treatment with simvastatin. On the whole, our findings indicate that simvastatin exerts a protective effect against ionizing radiation-induced damage in the mouse thymus, which may be partially attributed to the activation of the AKT/sirtuin 1 pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Yang H, Huang F, Tao Y, Zhao X, Liao L and Tao X: Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice. Int J Mol Med 40: 762-770, 2017.
APA
Yang, H., Huang, F., Tao, Y., Zhao, X., Liao, L., & Tao, X. (2017). Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice. International Journal of Molecular Medicine, 40, 762-770. https://doi.org/10.3892/ijmm.2017.3047
MLA
Yang, H., Huang, F., Tao, Y., Zhao, X., Liao, L., Tao, X."Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice". International Journal of Molecular Medicine 40.3 (2017): 762-770.
Chicago
Yang, H., Huang, F., Tao, Y., Zhao, X., Liao, L., Tao, X."Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice". International Journal of Molecular Medicine 40, no. 3 (2017): 762-770. https://doi.org/10.3892/ijmm.2017.3047
Copy and paste a formatted citation
x
Spandidos Publications style
Yang H, Huang F, Tao Y, Zhao X, Liao L and Tao X: Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice. Int J Mol Med 40: 762-770, 2017.
APA
Yang, H., Huang, F., Tao, Y., Zhao, X., Liao, L., & Tao, X. (2017). Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice. International Journal of Molecular Medicine, 40, 762-770. https://doi.org/10.3892/ijmm.2017.3047
MLA
Yang, H., Huang, F., Tao, Y., Zhao, X., Liao, L., Tao, X."Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice". International Journal of Molecular Medicine 40.3 (2017): 762-770.
Chicago
Yang, H., Huang, F., Tao, Y., Zhao, X., Liao, L., Tao, X."Simvastatin ameliorates ionizing radiation-induced apoptosis in the thymus by activating the AKT/sirtuin 1 pathway in mice". International Journal of Molecular Medicine 40, no. 3 (2017): 762-770. https://doi.org/10.3892/ijmm.2017.3047
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