Investigations of the effects of the antimalarial drug dihydroartemisinin (DHA) using the Frog Embryo Teratogenesis Assay-Xenopus (FETAX)

摘要: Artemisinin derivatives are effective and safe drugs for treating malaria, but they not recommended during the first trimester of pregnancy because resorptions abnormalities observed in animal reproduction studies. Previous studies rats showed that artemisinin embryotoxicity derives from depletion primitive red blood cells (RBCs) over a narrow critical time window (gestation Days 9-14). In order to further investigate susceptibility RBCs artemisinins establish whether this is species-specific or inherent compound, we studied dihydroartemisinin (DHA), both drug its own right main metabolite current use, Frog Embryo Teratogenesis Assay-Xenopus (FETAX). This model readily allows investigation monitoring definitive RBCs. Effects on frog larvae exposed DHA 48 h early embryonic development, starting 24 post fertilization, were similar those rat embryos terms reduction number (clonally produced within ventral island). contrast, older (stage 47, at sites hematopoiesis) affected minimally subsequently recovered. Compared embryos, had no areas necrosis shared heart defects. The mitochondrion appeared be subcellular target, observations Plasmodium. These results implicate artemisinin-induced through perturbation metabolically active RBCs; whereas mode action does appear species-specific, stages varied between different species. duration exposure must considered evaluate clinical relevance these findings.