Selective toxicity of dihydroartemisinin on human CD34+ erythroid cell differentiation.

摘要: Artemisinins are safely used in the combination therapy for uncomplicated malaria, but their employment during pregnancy is still controversial. In fact, animal studies reported that active metabolite, dihydroartemisinin (DHA), causes embryonic erythrocytes depletion, when treatment performed a critical period of time. The present study investigates effect DHA on human developmental erythropoiesis order to characterize target erythroid stage and predict window susceptibility pregnancy. As model erythropoiesis, peripheral blood purified, CD34+ cells were committed towards (0.5 or 2 μM) was added different stages 14 days culture. Erythroid differentiation investigated by cytofluorimetric analysis Glycophorin A expression, morphological globin gene expression with real-time PCR. It found dependent maturation cells. fact pro- basophilic erythroblasts caused significant dose-dependent inhibition cell proliferation delay differentiation, as measured analysis, immunofluorescence genes contrast, stem early progenitors transient masked subsequent exponential growth. No observed mature stages. This first demonstration affects vitro, dose- time-dependent manner; population seems be pro-erythroblast erythroblast stage, suggesting toxicity limited primitive erythropoiesis. These findings outline relevance dosage timing prevent embryotoxicity support current WHO recommendations avoiding malaria artemisinins trimester