Cargando…

Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug s...

Descripción completa

Detalles Bibliográficos
Autores principales: Porto, Raquel, Mengarda, Ana C., Cajas, Rayssa A., Salvadori, Maria C., Teixeira, Fernanda S., Arcanjo, Daniel D. R., Siyadatpanah, Abolghasem, Pereira, Maria de Lourdes, Wilairatana, Polrat, de Moraes, Josué
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308662/
https://www.ncbi.nlm.nih.gov/pubmed/34358112
http://dx.doi.org/10.3390/ph14070686
_version_ 1783728334574714880
author Porto, Raquel
Mengarda, Ana C.
Cajas, Rayssa A.
Salvadori, Maria C.
Teixeira, Fernanda S.
Arcanjo, Daniel D. R.
Siyadatpanah, Abolghasem
Pereira, Maria de Lourdes
Wilairatana, Polrat
de Moraes, Josué
author_facet Porto, Raquel
Mengarda, Ana C.
Cajas, Rayssa A.
Salvadori, Maria C.
Teixeira, Fernanda S.
Arcanjo, Daniel D. R.
Siyadatpanah, Abolghasem
Pereira, Maria de Lourdes
Wilairatana, Polrat
de Moraes, Josué
author_sort Porto, Raquel
collection PubMed
description The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC(50)) and 90% (EC(90)) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.
format Online
Article
Text
id pubmed-8308662
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83086622021-07-25 Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni Porto, Raquel Mengarda, Ana C. Cajas, Rayssa A. Salvadori, Maria C. Teixeira, Fernanda S. Arcanjo, Daniel D. R. Siyadatpanah, Abolghasem Pereira, Maria de Lourdes Wilairatana, Polrat de Moraes, Josué Pharmaceuticals (Basel) Article The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC(50)) and 90% (EC(90)) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent. MDPI 2021-07-16 /pmc/articles/PMC8308662/ /pubmed/34358112 http://dx.doi.org/10.3390/ph14070686 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Porto, Raquel
Mengarda, Ana C.
Cajas, Rayssa A.
Salvadori, Maria C.
Teixeira, Fernanda S.
Arcanjo, Daniel D. R.
Siyadatpanah, Abolghasem
Pereira, Maria de Lourdes
Wilairatana, Polrat
de Moraes, Josué
Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni
title Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni
title_full Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni
title_fullStr Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni
title_full_unstemmed Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni
title_short Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni
title_sort antiparasitic properties of cardiovascular agents against human intravascular parasite schistosoma mansoni
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308662/
https://www.ncbi.nlm.nih.gov/pubmed/34358112
http://dx.doi.org/10.3390/ph14070686
work_keys_str_mv AT portoraquel antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni
AT mengardaanac antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni
AT cajasrayssaa antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni
AT salvadorimariac antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni
AT teixeirafernandas antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni
AT arcanjodanieldr antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni
AT siyadatpanahabolghasem antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni
AT pereiramariadelourdes antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni
AT wilairatanapolrat antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni
AT demoraesjosue antiparasiticpropertiesofcardiovascularagentsagainsthumanintravascularparasiteschistosomamansoni