Original Article

Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish

Qian Ba, Juan Duan, Jia-qiang Tian, Zi-liang Wang, Tao Chen, Xiao-guang Li, Pei-zhan Chen, Song-jie Wu, Li Xiang, Jing-quan Li, Rui-ai Chu, Hui Wang
DOI: 10.1038/aps.2013.48

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 RNAin 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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