Elimination of Schistosoma mansoni in infected mice by slow release of artemisone
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Date
2017Author
Gold, Daniel
Haynes, Richard K.
Wong, Ho Ning
Alian, Mohammed
Domb, Avraham
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The current treatment of schistosomiasis is based on the anti-helminthic drug praziquantel (PZQ). PZQ
affects only the adult stages of schistosomes. In addition, resistance to PZQ is emerging. We suggest a
drug, which could serve as a potential alternative or complement to PZQ, and as a means of treating
infections at earlier, pre-granuloma stage. Derivatives of the peroxidic antimalarial drug artemisinin have
been indicated as alternatives, because both plasmodia and schistosomes are blood-feeding parasites.
The mechanism of action of artemisinins is related to oxidative effects of the artemisinins on intracellular
reductants leading to formation of cytotoxic reactive oxygen species. We used artemisone, which has
improved pharmacokinetics and anti-plasmodial activity, and reduced toxicity compared to other artemisinins
in clinical use against malaria. We infected adult mice by subcutaneous injection of S. mansoni
cercariae (about 200) and treated them at various times post infection by the following methods: i.
artemisone suspension administered by gavage (400e450 mg/kg); ii. subcutaneous injection of a gel
containing a known concentration of artemisone (115e120 mg/kg); iii. subcutaneous insertion of the
drug incorporated in a solid polymer (56e60 mg/kg); iv. intraperitoneal injection of the drug solubilized
in DMSO (115e120 mg/kg). Drug administration in polymers was performed to enable slow release of the
artemisone that was verified in vivo and in vitro bioassays using drug-sensitive malaria parasites. We
found superior strong anti-schistosome effects up to a total reduction of worm number, mainly following
repetitive treatments with the drug absorbed in the polymers (73.1% and 95.9% reduction in mice treated
with artemisone in gel 7 and 14, and 21, 28 and 35 days post infection, respectively). The results indicate
that artemisone has a potent anti-schistosome activity. Its main importance in this context is its effectiveness
in treating hosts harboring juvenile schistosomes, before egg-deposition and induction of
deleterious immune responses
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http://hdl.handle.net/10394/24825https://www.sciencedirect.com/science/article/pii/S221132071730012X
https://doi.org/10.1016/j.ijpddr.2017.05.002
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