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Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation

文献类型：期刊论文

作者Gan, Lu1,2,3; Guo, Menghuan4; Si, Jing1,2,3; Zhang, Jinhua1,2,3; Liu, Zhiyuan5; Zhao, Jin6; Wang, Fang1,2,3; Yan, Junfang1,2,3; Li, Hongyan1,2,3; Zhang, Hong1,2,3
刊名ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
出版日期2019-12-04
卷号47期号:1页码:4202-4210
ISSN号2169-1401
关键词X-ray irradiation zebrafish phenformin neurodevelopmental protective effects
DOI10.1080/21691401.2019.1687505
通讯作者Zhang, Hong(zhangh@impcas.ac.cn)
英文摘要Radiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developmental toxicity in zebrafish embryos. Zebrafish embryos pre-treated with 25 mu M phenformin 1 h before x-ray irradiation were compared to irradiation-only embryos for mortality, hatching rate, morphology, spontaneous movement, heart beat, larval swimming, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), malondialdehyde content (MDA, a by-product of membrane lipid oxidation), and acetylcholinesterase (AChE) activity. In addition, expression levels of multiple genes related to neural development and apoptosis (sod2, bdnf, ache, p53, bax, and bcl-2) were compared by RT-PCR and associated protein expression levels by western blotting. Pre-treatment with phenformin increased hatching rate, spontaneous movement, heart beat, and larval motor activity, decreased mortality and malformation rate, increased SOD, CAT, and AChE activities, and reduced MDA compared to irradiation-only embryos. The mRNA expression levels of anti-apoptotic sod2, bdnf, ache, and bcl-2 were enhanced while mRNA expression of p53 and pro-apoptotic bax were reduced in the phenformin pre-treatment group. Further, p53, Bax, and gamma-H2AX (a biomarker of DNA damage) were downregulated while Bcl-2 and BDNF were upregulated by phenformin pre-treatment. Taken together, this study supports the protective efficacy of phenformin against radiation toxicity in zebrafish embryos by suppressing oxidative stress and ensuing apoptosis.
WOS关键词WHOLE-BRAIN IRRADIATION ; HIPPOCAMPAL NEUROGENESIS ; OXIDATIVE STRESS ; NEUROTROPHIC FACTOR ; DANIO-RERIO ; GAMMA-IRRADIATION ; DEVELOPMENTAL TOXICITY ; BEHAVIOR ; ADULT ; NEUROTOXICITY
资助项目Ministry of Science and Technology National Key RD Project[2018YFE0205100] ; National Natural Science Foundation of China[81960337] ; National Natural Science Foundation of China[31560254] ; National Natural Science Foundation of China[11605255] ; National Natural Science Foundation of China[11605289] ; Fundamental Research Funds for the Central Universities[31920160048]
WOS研究方向Biotechnology & Applied Microbiology ; Engineering ; Materials Science
语种英语
出版者TAYLOR & FRANCIS LTD
WOS记录号WOS:000496253100001
资助机构Ministry of Science and Technology National Key RD Project ; National Natural Science Foundation of China ; Fundamental Research Funds for the Central Universities
源URL[http://119.78.100.186/handle/113462/141584]  
专题中国科学院近代物理研究所
通讯作者Zhang, Hong
作者单位1.Chinese Acad Sci, Inst Modern Phys, Dept Radiat Med, Lanzhou 730000, Gansu, Peoples R China
2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Gansu, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Lanzhou Univ, Sch Pharm, Lanzhou, Gansu, Peoples R China
5.Northwest Minzu Univ, Coll Chem Engn, Lanzhou, Gansu, Peoples R China
6.Northwest Minzu Univ, Med Coll, Lanzhou, Gansu, Peoples R China
推荐引用方式
GB/T 7714		 Gan, Lu,Guo, Menghuan,Si, Jing,et al. Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation[J]. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY,2019,47(1):4202-4210.
APA Gan, Lu.,Guo, Menghuan.,Si, Jing.,Zhang, Jinhua.,Liu, Zhiyuan.,...&Zhang, Hong.(2019).Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation.ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY,47(1),4202-4210.
MLA Gan, Lu,et al."Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation".ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 47.1(2019):4202-4210.

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来源：近代物理研究所

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