The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni

Detalhes bibliográficos
Autor(a) principal: Gouveia, Maria João
Data de Publicação: 2019
Outros Autores: Brindley, Paul J., Azevedo, Carlos, Gärtner, Fátima, da Costa, José M. C., Vale, Nuno
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6602
Resumo: Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31221193/
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spelling The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoniAcetylcysteineAnimalsAntioxidantsAntiprotozoal AgentsArtesunateBiomphalariaDrug SynergismFemaleLarvaMalePlant ExtractsPraziquantelResveratrolSchistosoma mansoniSchistosomiasisInfecções Sistémicas e ZoonosesFree PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31221193/Background: Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. Despite its celebrated performance for treatment and control of schistosomiasis and other platyhelminth infections, praziquantel has some shortcomings and the inability of this drug to counteract disease sequelae prompts the need for novel therapeutic strategies. Methods: Using a host-parasite model involving Biomphalaria glabrata and Schistosoma mansoni we established mechanical transformation of S. mansoni cercariae into newly transformed schistosomula (NTS) and characterized optimal culture conditions. Thereafter, we investigated the antischistosomal activity and ability of the antioxidants N-acetylcysteine (NAC) and resveratrol (RESV) to augment the performance of praziquantel and/or artesunate (AS) against larval stages of the parasite. Drug effects were evaluated by using an automated microscopical system to study live and fixed parasites and by transmission electron microscopy (TEM). Results: Transformation rates of cercariae to schistosomula reached ~ 70% when the manipulation process was optimized. Several culture media were tested, with M199 supplemented with HEPES found to be suitable for S. mansoni NTS. Among the antioxidants studied, RESV alone or combined with anthelminthic drugs achieved better results rather N-acetylcysteine (NAC). TEM observations demonstrated that the combination of AS + RESV induced severe, extensive alterations to the tegument and subtegument of NTS when compared to the constituent compounds alone. Two anthelmintic-antioxidant combinations, praziquantel-resveratrol [combination index (CI) = 0.74] and artesunate-resveratrol (CI = 0.34) displayed moderate and strong synergy, respectively. Conclusions: The use of viability markers including staining with propidium iodide increased the accuracy of drug screening assays against S. mansoni NTS. The synergies observed might be the consequence of increased action by RESV on targets of AS and PZQ and/or they may act through concomitantly on discrete targets to enhance overall antischistosomal action. Combinations of active agents, preferably with discrete modes of action including activity against developmental stages and/or the potential to ameliorate infection-associated pathology, might be pursued in order to identify novel therapeutic interventions.NV acknowledges support from the Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER (European Union) through Project Number IF/00092/2014/CP1255/CT0004. NV thanks FCT by IF position, Fundação Manuel António da Mota (FMAM, Portugal) and Pfzer Portugal for research group support. JMCC thanks FCT for UID/Multi/00211/2019 and Strategic Project UI211. PJB acknowledges support from award RO1CA164719 from the National Cancer Institute (NCI), National Institutes of Health (NIH), USA. The contents of this report are solely the responsibility of the authors and do not necessarily represent the ofcial views of the FCT, FMAM, the NCI, or the NIH.BMCRepositório Científico do Instituto Nacional de SaúdeGouveia, Maria JoãoBrindley, Paul J.Azevedo, CarlosGärtner, Fátimada Costa, José M. C.Vale, Nuno2020-05-06T11:54:46Z2019-062019-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6602engParasit Vectors. 2019 Jun 20;12(1):309. doi: 10.1186/s13071-019-3566-91756-330510.1186/s13071-019-3566-9info: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:RCAAP2023-07-20T15:41:45Zoai:repositorio.insa.pt:10400.18/6602Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:40.915703Repositório 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 The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni
title The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni
spellingShingle The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni
Gouveia, Maria João
Acetylcysteine
Animals
Antioxidants
Antiprotozoal Agents
Artesunate
Biomphalaria
Drug Synergism
Female
Larva
Male
Plant Extracts
Praziquantel
Resveratrol
Schistosoma mansoni
Schistosomiasis
Infecções Sistémicas e Zoonoses
title_short The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni
title_full The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni
title_fullStr The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni
title_full_unstemmed The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni
title_sort The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni
author Gouveia, Maria João
author_facet Gouveia, Maria João
Brindley, Paul J.
Azevedo, Carlos
Gärtner, Fátima
da Costa, José M. C.
Vale, Nuno
author_role author
author2 Brindley, Paul J.
Azevedo, Carlos
Gärtner, Fátima
da Costa, José M. C.
Vale, Nuno
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Gouveia, Maria João
Brindley, Paul J.
Azevedo, Carlos
Gärtner, Fátima
da Costa, José M. C.
Vale, Nuno
dc.subject.por.fl_str_mv Acetylcysteine
Animals
Antioxidants
Antiprotozoal Agents
Artesunate
Biomphalaria
Drug Synergism
Female
Larva
Male
Plant Extracts
Praziquantel
Resveratrol
Schistosoma mansoni
Schistosomiasis
Infecções Sistémicas e Zoonoses
topic Acetylcysteine
Animals
Antioxidants
Antiprotozoal Agents
Artesunate
Biomphalaria
Drug Synergism
Female
Larva
Male
Plant Extracts
Praziquantel
Resveratrol
Schistosoma mansoni
Schistosomiasis
Infecções Sistémicas e Zoonoses
description Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31221193/
publishDate 2019
dc.date.none.fl_str_mv 2019-06
2019-06-01T00:00:00Z
2020-05-06T11:54:46Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/6602
url http://hdl.handle.net/10400.18/6602
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Parasit Vectors. 2019 Jun 20;12(1):309. doi: 10.1186/s13071-019-3566-9
1756-3305
10.1186/s13071-019-3566-9
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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