Artesunate-induced depletion of embryonic erythroblasts precedes embryolethality and teratogenicity in vivo

Abstract

In summary, embryonic erythroblasts are the primary target of ART toxicity in the rat embryo after in vivo treatment, preceding embryolethality and malformations.

Therapeutic and Toxicological Inhibition of Vasculogenesis and Angiogenesis Mediated by Artesunate, a Compound with Both Antimalarial and Anticancer Efficacy

“…A summary of the research findings and possible mechanisms of artemisinin drugs in the embryotoxicity studies in vitro and in vivo (Clark et al, 2009;Efferth & Kaina 2010;Finaurini et al, 2010;Longo et al, 2006aLongo et al, , 2006bLongo et al, , 2008Wartenberg et al, 2003;White et al, 2008) 2.2.1 Inhibitory effects of AS/DHA on hematopoiesis AS is embryolethal and teratogenic in rats, with a very narrow window of sensitivity between days 10-14 of gestation (Clark et al, 2004;Li et al, 2009;White et al, 2006). Further studies with a single oral dose of 17 mg/kg AS on gestational day (GD) 10-11 demonstrated that a paling of the visceral yolk sacs was observed within 3-6 hr after treatment.…”

“…In rats these findings were attributed to cell death resulting from anemia and hypoxia (Longo et al, 2006a); here, frog larvae death may be secondary to anemia. Potentially larvae death may not be mediated by cell death but rather by altered intracardiac hemodynamics due to RBC degeneration, as speculated by White et al (2006). In embryotoxicity studies conducted with DHA administered at GD 9, the yolk sac was shown to be fully vascularized.…”

“…AS is completely converted to DHA and is basically a prodrug of DHA. Also, DHA was shown to be more effective than AS in inhibition of angiogenesis and vasculogenesis in vitro (Longo et al, 2006a;2006b;Chen et al, 2004b;White et al, 2006). In addition without DHA formation, the embryotoxicit y o f A R T s c a n b e r e d u c e d b y u s i n g artemisone, which has significantly less anti-angiogenic activity than DHA.…”

“…Also, DHA was shown to be more effective than AS in inhibition of angiogenesis and vasculogenesis in vitro (Longo et al, 2006a;2006b;Chen et al, 2004;White et al, 2006). In addition, , the embryotoxicity and neurotoxicity of artemisinins can be reduced by using artemisone, which is a novel derivative of artemisinin that is not metabolized to DHA (Figure 1) (D'Alessandro et al, 2007;Schmuck et al, 2009).…”

Effect of interaction of magnetic nanoparticles of Fe3O4 and artesunate on apoptosis of K562 cells

“…Recently, several studies showed that ART could inhibit the growth of various carcinoma cell lines [1][2][3] and suppress tumor cell proliferation by inducing apoptosis, 4 indicating that ART may be a promising novel candidate for leukemia therapy. However, a variety of lines of evidence indicate that ART inhibited cell proliferation in a dose-dependent manner, and a high concentration of ART induced embryo toxicity, [5][6][7] reversible renal damage toxicity, 8 and toxicity to bone development, 9 which limit the usefulness of ART. To minimize side effects associated with dosage during chemotherapy, a promising approach is to combine a conventional chemotherapy with new strategies to maximize efficacy of tumor treatment through inducing cell apoptosis.…”