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

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 tre...

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Autores principales: Gold, Daniel, Alian, Mohammed, Domb, Avraham, Karawani, Yara, Jbarien, Maysa, Chollet, Jacques, Haynes, Richard K., Wong, Ho Ning, Buchholz, Viola, Greiner, Andreas, Golenser, Jacob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430492/
https://www.ncbi.nlm.nih.gov/pubmed/28511056
http://dx.doi.org/10.1016/j.ijpddr.2017.05.002
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author Gold, Daniel
Alian, Mohammed
Domb, Avraham
Karawani, Yara
Jbarien, Maysa
Chollet, Jacques
Haynes, Richard K.
Wong, Ho Ning
Buchholz, Viola
Greiner, Andreas
Golenser, Jacob
author_facet Gold, Daniel
Alian, Mohammed
Domb, Avraham
Karawani, Yara
Jbarien, Maysa
Chollet, Jacques
Haynes, Richard K.
Wong, Ho Ning
Buchholz, Viola
Greiner, Andreas
Golenser, Jacob
author_sort Gold, Daniel
collection PubMed
description 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.
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spelling pubmed-54304922017-05-24 Elimination of Schistosoma mansoni in infected mice by slow release of artemisone Gold, Daniel Alian, Mohammed Domb, Avraham Karawani, Yara Jbarien, Maysa Chollet, Jacques Haynes, Richard K. Wong, Ho Ning Buchholz, Viola Greiner, Andreas Golenser, Jacob Int J Parasitol Drugs Drug Resist Article 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. Elsevier 2017-05-04 /pmc/articles/PMC5430492/ /pubmed/28511056 http://dx.doi.org/10.1016/j.ijpddr.2017.05.002 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Gold, Daniel
Alian, Mohammed
Domb, Avraham
Karawani, Yara
Jbarien, Maysa
Chollet, Jacques
Haynes, Richard K.
Wong, Ho Ning
Buchholz, Viola
Greiner, Andreas
Golenser, Jacob
Elimination of Schistosoma mansoni in infected mice by slow release of artemisone
title Elimination of Schistosoma mansoni in infected mice by slow release of artemisone
title_full Elimination of Schistosoma mansoni in infected mice by slow release of artemisone
title_fullStr Elimination of Schistosoma mansoni in infected mice by slow release of artemisone
title_full_unstemmed Elimination of Schistosoma mansoni in infected mice by slow release of artemisone
title_short Elimination of Schistosoma mansoni in infected mice by slow release of artemisone
title_sort elimination of schistosoma mansoni in infected mice by slow release of artemisone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430492/
https://www.ncbi.nlm.nih.gov/pubmed/28511056
http://dx.doi.org/10.1016/j.ijpddr.2017.05.002
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