title: Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish.
abstract: OBJECTIVE
  To investigate the embryotoxicity of dihydroartemisinin (DHA), the main active metabolite of artemisinin, in zebrafish, and explore the corresponding mechanisms.
  
  
  METHODS
  The embryos of wild type and TG (flk1:GFP) transgenic zebrafish were exposed to DHA. Developmental phenotypes of the embryos were observed. Development of blood vessels was directly observed in living embryos of TG (flk1:GFP) transgenic zebrafish under fluorescence microscope. The expression of angiogenesis marker genes vegfa, flk1, and flt1 in the embryos was detected using real-time PCR and RNA in situ hybridization assays.
  
  
  RESULTS
  Exposure to DHA (1-10 mg/L) dose-dependently caused abnormal zebrafish embryonic phenotypes in the early developmental stage. Furthermore, exposure to DHA (10 mg/L) resulted in more pronounced embryonic angiogenesis in TG (flk1:GFP) zebrafish line. Exposure to DHA (10 mg/L) significantly increased the mRNA expression of vegfa, flk1, and flt1 in the embryos. Knockdown of the flk1 protein partially blocked the effects of DHA on embryogenesis.
  
  
  CONCLUSIONS
  DHA causes abnormal embryonic phenotypes and promotes angiogenesis in zebrafish early embryonic development, demonstrating the potential embryotoxicity of DHA.
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ba
authors.forename: Juan
authors.initials: J
authors.lastname: Duan
authors.forename: Jia-qiang
authors.initials: JQ
authors.lastname: Tian
authors.forename: Zi-liang
authors.initials: ZL
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Xiao-guang
authors.initials: XG
authors.lastname: Li
authors.forename: Pei-zhan
authors.initials: PZ
authors.lastname: Chen
authors.forename: Song-jie
authors.initials: SJ
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Xiang
authors.forename: Jing-quan
authors.initials: JQ
authors.lastname: Li
authors.forename: Rui-ai
authors.initials: RA
authors.lastname: Chu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019306:Artemisia / Q000633:toxicity*; D037621:Artemisinins / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000196:embryology* / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000473:pathology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
chemical_list: D037621:Artemisinins; C039060:artenimol