Elimination of Schistosoma mansoni in infected mice by slow release of artemisone

Abstract

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 (400–450 mg/kg); ii. subcutaneous injection of a gel containing a known concentration of artemisone (115–120 mg/kg); iii. subcutaneous insertion of the drug incorporated in a solid polymer (56–60 mg/kg); iv. intraperitoneal injection of the drug solubilized in DMSO (115–120 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.

Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy

“…Likewise, a single oral dose of artesunate (400 mg/kg in 3% ethanol and 7% Tween 80) given 21 days post-infection, yielded a 66% reduction of worm load [10]. A similar procedure using other artemisinin derivatives (artemiside, artemisone, CKWO3 and artemether) yielded more than 90% reduction [5]. Significant reduction of S. mansoni load was found in infected mice treated with new artemisinin derivatives, artesunic acid and dihydroartemisinin acetate [12].…”

Schistosomal extracellular vesicle‐enclosed miRNAs modulate host T helper cell differentiation

“…Details of upkeep of the life cycle relied on description by Gold et al [84] and performed at Tel Aviv University (Tel Aviv University ethical committee number 01-13-076). Six-week-old male ICR mice were purchased from Harlan Laboratories (Rehovot, Israel) and infected individually by subcutaneous injection with the parasite's cercariae obtained from infected snails which were raised and kept at 26°C in aeriated aquaria.…”

The anti-mycobacterial activity ofArtemisia annuaL is based on deoxyartemisinin and artemisinic acid

“…We observed that the anti-mycobacterial activity of both Artemisia-derived natural products was not dependent on an endoperoxide bridge. Artemisinin, artesunate, artemisone, dihydroartemisinin and artemether, all with endoperoxide bridges, have shown to be effective against S. mansoni , through the peroxidative activity [10,11]. However, we found neither deoxyartemisinin nor artemisinic acid exhibited any effect on S. mansoni viability or mobility (data not shown), which could be caused by the lack of endoperoxide bridges in both compounds.…”