Radioprotective effect of a pan-caspase inhibitor in a novel model of radiation injury to the nucleus of the abducens nerve

  • Authors:
    • Jianguo Li
    • Li Lin
    • Liqing Du
    • Chang Xu
    • Yan Wang
    • Jia Cao
    • Qin Wang
    • Feiyue Fan
    • Xiaoping Wang
    • Yafei Wang
    • Qiang Liu
  • View Affiliations

  • Published online on: June 16, 2014     https://doi.org/10.3892/mmr.2014.2334
  • Pages: 1433-1437
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Abstract

There is increasing evidence that neuronal cell death occurs via extrinsic (death receptors) and intrinsic (mitochondria) pathways. Radiation induces caspase activation fundamentally via the mitochondrial pathway. Caspases are the key regulators of apoptosis. Healthy male Sprague‑Dawley rats were used in the present study to examine the radioprotective effect of a type of pan-caspase inhibitor, z-VAD-fmk, following radiation, to investigate the effects of caspase blockade in a model of the nucleus of the abducens nerve. z-VAD-fmk was injected intracerebroventricularly as a bolus injection (0.2 µg/h for 1 h) into rats prior to exposure to radiation. Irradiation was conducted at room temperature at a dose of radiation of 4 Gy. The present study performed immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and western blot analysis and identified no significant changes in the expression of the X-linked inhibitor of apoptosis protein (XIAP) following radiation (P>0.05). As compared with the radiation alone group, the quantification of TUNEL-positive neurons was reduced in z-VAD‑fmk-treated animals following radiation (P<0.01). Inhibition of caspase induced by z-VAD‑fmk reduced the expression and activation of caspase-3, -8 and -9 (P<0.01). z-VAD-fmk effectively prevented radiation-induced apoptosis and this caspase inhibitor may be a potential therapeutic target in the treatment of brain radiation injury. The nucleus of the abducens nerve may be used as a radiation injury model, providing visual information and data on the apoptotic morphology of the abducens nucleus.
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September-2014
Volume 10 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Li J, Lin L, Du L, Xu C, Wang Y, Cao J, Wang Q, Fan F, Wang X, Wang Y, Wang Y, et al: Radioprotective effect of a pan-caspase inhibitor in a novel model of radiation injury to the nucleus of the abducens nerve. Mol Med Rep 10: 1433-1437, 2014.
APA
Li, J., Lin, L., Du, L., Xu, C., Wang, Y., Cao, J. ... Liu, Q. (2014). Radioprotective effect of a pan-caspase inhibitor in a novel model of radiation injury to the nucleus of the abducens nerve. Molecular Medicine Reports, 10, 1433-1437. https://doi.org/10.3892/mmr.2014.2334
MLA
Li, J., Lin, L., Du, L., Xu, C., Wang, Y., Cao, J., Wang, Q., Fan, F., Wang, X., Wang, Y., Liu, Q."Radioprotective effect of a pan-caspase inhibitor in a novel model of radiation injury to the nucleus of the abducens nerve". Molecular Medicine Reports 10.3 (2014): 1433-1437.
Chicago
Li, J., Lin, L., Du, L., Xu, C., Wang, Y., Cao, J., Wang, Q., Fan, F., Wang, X., Wang, Y., Liu, Q."Radioprotective effect of a pan-caspase inhibitor in a novel model of radiation injury to the nucleus of the abducens nerve". Molecular Medicine Reports 10, no. 3 (2014): 1433-1437. https://doi.org/10.3892/mmr.2014.2334