title: Radioprotective effect of a pan-caspase inhibitor in a novel model of radiation injury to the nucleus of the abducens nerve.
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.
authors.affiliation: Department of Human Anatomy, The Medical School of Inner Mongolia University for the Nationalities, Neimenggu, Tongliao 028041, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Du
authors.affiliation: Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.affiliation: Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Feiyue
authors.initials: F
authors.lastname: Fan
authors.affiliation: Department of Human Anatomy, The Medical School of Inner Mongolia University for the Nationalities, Neimenggu, Tongliao 028041, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, P.R. China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000010:Abducens Nerve / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D011832:Radiation Injuries / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; C494837:Xiap protein, rat; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9