Galal Shereen Mohamed, Abdel-Rafei Mohamed Khairy, Hasan Hesham Farouk
a Health Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, P.O. Box 29, Nasr City, Cairo, Egypt.
b Radiation Biology Department, National Center for Radiation Research and Technology, Atomic Energy Authority, P.O. Box 29, Nasr City, Cairo, Egypt.
Can J Physiol Pharmacol. 2018 May;96(5):442-458. doi: 10.1139/cjpp-2017-0578. Epub 2017 Dec 8.
The present investigation aimed to evaluate the radiomitigative efficacy of the recombinant human erythropoietin (EPO) against acute radiation syndrome (ARS) in a rat model. Rats were irradiated with a single sublethal dose of γ-radiation (7 Gy; total body irradiation; TBI) on the 1st day of experimental course, then received EPO (5000 IU/kg; i.p.) 24 h after irradiation, and rats were observed for 30 days of survival analysis. Administration of EPO improved 30-day survival, alleviated TBI-induced myelosuppression and pancytopenia, by augmenting lymphocytes and other white blood cells in the peripheral blood of rats, while bone marrow and spleen cellularity were restored. EPO post-exposure treatment alleviated hepatotoxicity biomarkers and restored splenic function. EPO abrogated radiation-induced oxidative stress through the upregulation of the cholinergic anti-inflammatory nicotinic acetylcholine receptor (α-7-nAChR) and the pro-survival Janus kinase-2 and signal transducers and activators of transcription JAK-2/STAT-3 signaling mediated via enhancing nuclear factor erythroid-2 related factor-2 (Nrf-2) cytoprotective machinery in liver and spleen of irradiated rats. Moreover, EPO treatment prevented hepatic and splenic apoptosis. The present study establishes the implication of α-7-nAChR-JAK-2/STAT-3-Nrf-2 signaling cascade in the radiomitigative potential of EPO against ARS.
本研究旨在评估重组人促红细胞生成素（EPO）在大鼠模型中对急性放射综合征（ARS）的辐射防护效果。在实验过程的第1天，用单次亚致死剂量的γ射线（7 Gy；全身照射；TBI）照射大鼠，然后在照射后24小时给予EPO（5000 IU/kg；腹腔注射），并对大鼠进行30天的生存分析。给予EPO可提高30天生存率，减轻TBI诱导的骨髓抑制和全血细胞减少，增加大鼠外周血中的淋巴细胞和其他白细胞，同时恢复骨髓和脾脏细胞数量。EPO暴露后治疗减轻了肝毒性生物标志物并恢复了脾脏功能。EPO通过上调胆碱能抗炎烟碱乙酰胆碱受体（α-7-nAChR）以及通过增强受辐射大鼠肝脏和脾脏中的核因子红细胞2相关因子2（Nrf-2）细胞保护机制介导的促生存Janus激酶-2和信号转导子及转录激活子JAK-2/STAT-3信号，消除了辐射诱导氧化应激。此外，EPO治疗可预防肝脏和脾脏的凋亡。本研究证实了α-7-nAChR-JAK-2/STAT-3-Nrf-2信号级联在EPO对ARS的辐射防护潜力中的作用。
