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

doi:10.1080/21691401.2019.1687505

	Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation
	Gan, Lu 1,2,3; Guo, Menghuan 4; Si, Jing 1,2,3; Zhang, Jinhua 1,2,3; Liu, Zhiyuan 5; Zhao, Jin 6; Wang, Fang 1,2,3; Yan, Junfang 1,2,3; Li, Hongyan 1,2,3; Zhang, Hong 1,2,3
刊名	ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
	2019-12-04
卷号	47 期号:1 页码:4202-4210
关键词	X-ray irradiation zebrafish phenformin neurodevelopmental protective effects
ISSN号	2169-1401
DOI	10.1080/21691401.2019.1687505
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.
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关键词	WHOLE-BRAIN IRRADIATION ; HIPPOCAMPAL NEUROGENESIS ; OXIDATIVE STRESS ; NEUROTROPHIC FACTOR ; DANIO-RERIO ; GAMMA-IRRADIATION ; DEVELOPMENTAL TOXICITY ; BEHAVIOR ; ADULT ; NEUROTOXICITY
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
内容类型	期刊论文
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.