Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish

被引：15

作者：

Ba, Qian ^{[1
,2
]}

Duan, Juan ^{[1
]}

Tian, Jia-qiang ^{[1
]}

Wang, Zi-liang ^{[1
]}

Chen, Tao ^{[1
]}

Li, Xiao-guang ^{[1
]}

Chen, Pei-zhan ^{[1
]}

Wu, Song-jie ^{[1
]}

Xiang, Li ^{[1
]}

Li, Jing-quan ^{[1
,2
]}

Chu, Rui-ai ^{[1
,2
]}

Wang, Hui ^{[1
,2
]}

机构：

[1] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Food Safety Res,Inst Nutr Sci, Shanghai 200031, Peoples R China

[2] Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing 100021, Peoples R China

来源：

ACTA PHARMACOLOGICA SINICA | 2013年 / 34卷 / 08期

关键词：

artemisinin; dihydroartemisinin; zebrafish; flk1; VEGF; angiogenesis; embryotoxicity; ENDOTHELIAL GROWTH-FACTOR; LEUKEMIA K562 CELLS; ANTIMALARIAL-DRUG; FACTOR EXPRESSION; IN-VIVO; ARTEMISININ; ARTESUNATE; TOXICITY; COMBINATION; DERIVATIVES;

D O I：

10.1038/aps.2013.48

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

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.

引用

页码：1101 / 1107

页数：7

共 25 条

[1]

Dihydroartemisinin Exerts Its Anticancer Activity through Depleting Cellular Iron via Transferrin Receptor-1 [J].