Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish
- Authors
- Ba, Q., Duan, J., Tian, J.Q., Wang, Z.L., Chen, T., Li, X.G., Chen, P.Z., Wu, S.J., Xiang, L., Li, J.Q., Chu, R.A., and Wang, H.
- ID
- ZDB-PUB-130703-41
- Date
- 2013
- Source
- Acta Pharmacologica Sinica 34(8): 1101-7 (Journal)
- Registered Authors
- Li, Xiang, Wang, Hui
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Artemisia/toxicity*
- Artemisinins/toxicity*
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/embryology*
- Embryo, Nonmammalian/pathology
- Embryonic Development/drug effects
- Embryonic Development/physiology
- Neovascularization, Pathologic/chemically induced*
- Neovascularization, Pathologic/pathology
- Zebrafish/embryology*
- Zebrafish/genetics
- PubMed
- 23708556 Full text @ Acta Pharmacol. Sin.
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.