Artemisinin compounds are highly effective and safe antimalarial drugs which are indispensable for the treatment and control of malaria. However, this class of drugs is not currently used during the first trimester of pregnancy because of the birth defects and embryo death observed in animal reproduction studies. In animals, the primary event linked to toxicity of artemisinin compounds during early development is depletion of the primitive erythroblasts. In this study, zebrafish was used as a model to analyze the mechanisms of erythroblasts toxicity elicited by artemisinin during embryo development.

The standard fish embryo toxicity assay was performed and zebrafish embryo mortality, erythroblasts formation and haemoglobin (Hb) content were evaluated.

Exposure of zebrafish embryos to artemisinin caused a dose-dependent increase in mortality. Surviving embryos showed malformations, such as pericardium edema, abnormal heart, reduced heartbeat and spine curvature. Furthermore, drug exposure led to severe specific erythropoietic cell depletion and linear decrease in Hb content.

In summary, our studies show that artemisinin induces developmental toxicity in zebrafish embryos because of depletion of the embryonic erythroblasts. This mode of action is similar to that described in previous studies from other species. Our results suggest that the zebrafish embryo toxicity assay can be systematically used to screen novel artemisinin compounds for embryotoxicity.