Combination anthelmintic/antioxidant activity against schistosoma mansoni

Detalhes bibliográficos
Autor(a) principal: Gouveia, M
Data de Publicação: 2019
Outros Autores: Brindley, P, Rinaldi, G, Gärtner, F, Costa, J, Vale, N
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/136293
Resumo: Schistosomiasis is a major neglected tropical disease. Treatment for schistosomiasis with praziquantel (PZQ), which is effective against the parasite, by itself is not capable to counteract infection-associated disease lesions including hepatic fibrosis. There is a pressing need for novel therapies. Due to their biological properties, antioxidant biomolecules might be useful in treating and reverting associated pathological sequelae. Here, we investigated a novel therapy approach based on a combination of anthelmintic drugs with antioxidant biomolecules. We used a host-parasite model involving Bioamphalaria glabrata and newly transformed schistosomula (NTS) of Schistosoma mansoni. For in vitro drug screening assays, was selected several antioxidants and evaluated not only antischistosomal activity but also ability to enhance activity of the anthelmintic drugs praziquantel (PZQ) and artesunate (AS). The morphological alterations induced by compounds alone/combined were assessed on daily basis using an inverted and automated microscope to quantify NTS viability by a fluorometric-based method. The findings indicated that not only do some antioxidants improve antischistosomal activity of the two anthelmintics, but they exhibit activity per se, leading to high mortality of NTS post-exposure. The combination index (CI) of PZQ + Mel (CI = 0.80), PZQ + Resv (CI = 0.74), AS + Resv (CI = 0.34), AS + NAC (CI = 0.89), VDT + Flav (CI = 1.03) and VDT + Resv (CI = 1.06) reveal that they display moderate to strong synergism. The combination of compounds with discrete mechanisms of action might provide a valuable adjunct to contribution for treatment of schistosomiasis-associated disease.
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spelling Combination anthelmintic/antioxidant activity against schistosoma mansoniAnthelmintic drugAnticancer drugAntioxidant biomoleculesCombination therapyDrug repurposingNewly transformed schistosomulaSchistosoma mansoniSchistosomiasis is a major neglected tropical disease. Treatment for schistosomiasis with praziquantel (PZQ), which is effective against the parasite, by itself is not capable to counteract infection-associated disease lesions including hepatic fibrosis. There is a pressing need for novel therapies. Due to their biological properties, antioxidant biomolecules might be useful in treating and reverting associated pathological sequelae. Here, we investigated a novel therapy approach based on a combination of anthelmintic drugs with antioxidant biomolecules. We used a host-parasite model involving Bioamphalaria glabrata and newly transformed schistosomula (NTS) of Schistosoma mansoni. For in vitro drug screening assays, was selected several antioxidants and evaluated not only antischistosomal activity but also ability to enhance activity of the anthelmintic drugs praziquantel (PZQ) and artesunate (AS). The morphological alterations induced by compounds alone/combined were assessed on daily basis using an inverted and automated microscope to quantify NTS viability by a fluorometric-based method. The findings indicated that not only do some antioxidants improve antischistosomal activity of the two anthelmintics, but they exhibit activity per se, leading to high mortality of NTS post-exposure. The combination index (CI) of PZQ + Mel (CI = 0.80), PZQ + Resv (CI = 0.74), AS + Resv (CI = 0.34), AS + NAC (CI = 0.89), VDT + Flav (CI = 1.03) and VDT + Resv (CI = 1.06) reveal that they display moderate to strong synergism. The combination of compounds with discrete mechanisms of action might provide a valuable adjunct to contribution for treatment of schistosomiasis-associated disease.MDPI20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/136293eng2218-273X10.3390/biom9020054Gouveia, MBrindley, PRinaldi, GGärtner, FCosta, JVale, Ninfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T14:21:41Zoai:repositorio-aberto.up.pt:10216/136293Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:59:37.966282Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Combination anthelmintic/antioxidant activity against schistosoma mansoni
title Combination anthelmintic/antioxidant activity against schistosoma mansoni
spellingShingle Combination anthelmintic/antioxidant activity against schistosoma mansoni
Gouveia, M
Anthelmintic drug
Anticancer drug
Antioxidant biomolecules
Combination therapy
Drug repurposing
Newly transformed schistosomula
Schistosoma mansoni
title_short Combination anthelmintic/antioxidant activity against schistosoma mansoni
title_full Combination anthelmintic/antioxidant activity against schistosoma mansoni
title_fullStr Combination anthelmintic/antioxidant activity against schistosoma mansoni
title_full_unstemmed Combination anthelmintic/antioxidant activity against schistosoma mansoni
title_sort Combination anthelmintic/antioxidant activity against schistosoma mansoni
author Gouveia, M
author_facet Gouveia, M
Brindley, P
Rinaldi, G
Gärtner, F
Costa, J
Vale, N
author_role author
author2 Brindley, P
Rinaldi, G
Gärtner, F
Costa, J
Vale, N
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Gouveia, M
Brindley, P
Rinaldi, G
Gärtner, F
Costa, J
Vale, N
dc.subject.por.fl_str_mv Anthelmintic drug
Anticancer drug
Antioxidant biomolecules
Combination therapy
Drug repurposing
Newly transformed schistosomula
Schistosoma mansoni
topic Anthelmintic drug
Anticancer drug
Antioxidant biomolecules
Combination therapy
Drug repurposing
Newly transformed schistosomula
Schistosoma mansoni
description Schistosomiasis is a major neglected tropical disease. Treatment for schistosomiasis with praziquantel (PZQ), which is effective against the parasite, by itself is not capable to counteract infection-associated disease lesions including hepatic fibrosis. There is a pressing need for novel therapies. Due to their biological properties, antioxidant biomolecules might be useful in treating and reverting associated pathological sequelae. Here, we investigated a novel therapy approach based on a combination of anthelmintic drugs with antioxidant biomolecules. We used a host-parasite model involving Bioamphalaria glabrata and newly transformed schistosomula (NTS) of Schistosoma mansoni. For in vitro drug screening assays, was selected several antioxidants and evaluated not only antischistosomal activity but also ability to enhance activity of the anthelmintic drugs praziquantel (PZQ) and artesunate (AS). The morphological alterations induced by compounds alone/combined were assessed on daily basis using an inverted and automated microscope to quantify NTS viability by a fluorometric-based method. The findings indicated that not only do some antioxidants improve antischistosomal activity of the two anthelmintics, but they exhibit activity per se, leading to high mortality of NTS post-exposure. The combination index (CI) of PZQ + Mel (CI = 0.80), PZQ + Resv (CI = 0.74), AS + Resv (CI = 0.34), AS + NAC (CI = 0.89), VDT + Flav (CI = 1.03) and VDT + Resv (CI = 1.06) reveal that they display moderate to strong synergism. The combination of compounds with discrete mechanisms of action might provide a valuable adjunct to contribution for treatment of schistosomiasis-associated disease.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/10216/136293
url https://hdl.handle.net/10216/136293
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2218-273X
10.3390/biom9020054
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv MDPI
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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