Elimination of Schistosoma mansoni in infected mice by slow release of artemisone. Issue 2 (August 2017)

• Record Type: Journal Article
• Authors: Gold, Daniel; Alian, Mohammed; Domb, Avraham; Karawani, Yara; Jbarien, Maysa; Chollet, Jacques; Haynes, Richard K.; Wong, Ho Ning; Buchholz, Viola; Greiner, Andreas; Golenser, Jacob
• Is Part Of: International journal for parasitology. Volume 7:Issue 2(2017)
• Page Start: 241
• Page End: 247
• Publication Date: 2017-08
• Subjects: Schistosoma -- Treatment -- Slow release -- Artemisone; Parasitic diseases -- Chemotherapy -- Periodicals; Drug resistance -- Periodicals; 616.96061
• DOI: 10.1016/j.ijpddr.2017.05.002
• Languages: English
• ISSNs: 2211-3207

Abstract

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. Graphical abstract: Highlights: Praziquantel is mainly active against adult worms, unlike artemisone. Improved treatment of all Schistosoma stages, using artemisone, is suggested. Treatment in the mouse model consists of slowly released drug from injected polymer.