Abstract
Aim:
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.
Conclusion:
DHA causes abnormal embryonic phenotypes and promotes angiogenesis in zebrafish early embryonic development, demonstrating the potential embryotoxicity of DHA.
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Acknowledgements
We thank Dr Ting-xi LIU (Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) for the kind gift of the TG (flk1: GFP) transgenic zebrafish line. This study was supported by grants from the Ministry of Science and Technology of China (2012BAK01B00, 2011BAK10B00, and 2009CB919000), the National Natural Science Foundation (81125020, 91029715, 31070680, 31101261, 81242002, and 31200569), the Science and Technology Commission of Shanghai Municipality (12XD1407000, 12431900500, and 10391902100), Xuhui Central Hospital (CRC2011001 and CRC2011004), Director Foundation (20090101), and the Key Labortory of Food Safety Research of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
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Ba, Q., Duan, J., Tian, Jq. et al. Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish. Acta Pharmacol Sin 34, 1101–1107 (2013). https://doi.org/10.1038/aps.2013.48
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DOI: https://doi.org/10.1038/aps.2013.48
