Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms

Detalhes bibliográficos
Autor(a) principal: Almeida, Giuliana Teixeira de
Data de Publicação: 2015
Outros Autores: Lage, Regina Coeli Gonçalves, Anderson, Leticia, Venancio, Thiago Motta, Nakaya, Helder Takashi Imoto, Miyasato, Patrícia Aoki, Rofatto, Henrique Krambeck, Zerlotini, Adhemar, Nakano, Eliana, Oliveira, Guilherme Corrêa de, Almeida, Sergio Verjovski
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/13549
Resumo: Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil
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spelling Almeida, Giuliana Teixeira deLage, Regina Coeli GonçalvesAnderson, LeticiaVenancio, Thiago MottaNakaya, Helder Takashi ImotoMiyasato, Patrícia AokiRofatto, Henrique KrambeckZerlotini, AdhemarNakano, ElianaOliveira, Guilherme Corrêa deAlmeida, Sergio Verjovski2016-04-05T19:03:07Z2016-04-05T19:03:07Z2015ALMEIDA, Giuliana Teixeira de et al. Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms. PLoS Negl Trop Dis., vol. 9, n. 9, art. e0004086, 2015.1935-2735https://www.arca.fiocruz.br/handle/icict/1354910.1371/journal.pntd.0004086engPublic Library of ScienceSynergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Wormsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo de Genomica e Biologia Computacional. Belo Horizonte, MG, BrasilUniversidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, BrasilUniversidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, BrasilUniversidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, BrasilInstituto Butantan. São Paulo, SP, BrasilInstituto Butantan. São Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo de Genomica e Biologia Computacional. Belo Horizonte, MG, BrasilInstituto Butantan. São Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo de Genomica e Biologia Computacional. Belo Horizonte, MG, Brasil/ Vale Technology Institute. Belém, Pará, BrasilUniversidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil /Instituto Butantan. São Paulo, SP, BrasilBACKGROUND: Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis. METHODOLOGY: We used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay. PRINCIPAL FINDINGS: We identified sets of genes that were affected by PZQ in paired and unpaired mature females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired mature females), indicating that PZQ effects are heavily influenced by the mating status. We also identified genes that were similarly affected by PZQ in males and females. Functional analyses of gene interaction networks were performed with parasite genes that were differentially expressed upon PZQ treatment, searching for proteins encoded by these genes whose human homologs are targets of different drugs used for other diseases. Based on these results, OMP, a widely prescribed proton pump inhibitor known to target the ATP1A2 gene product, was chosen and tested. Sublethal doses of PZQ combined with OMP significantly increased worm mortality in vitro when compared with PZQ or OMP alone, thus evidencing a synergistic effect. CONCLUSIONS: Functional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with either drug alone.SchistosomiasisS. mansoniPraziquantelenzyme E2info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/13549/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSynergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms.pdfSynergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms.pdfapplication/pdf5155518https://www.arca.fiocruz.br/bitstream/icict/13549/2/Synergy%20of%20Omeprazole%20and%20Praziquantel%20In%20Vitro%20Treatment%20against%20Schistosoma%20mansoni%20Adult%20Worms.pdf8006bc4d9179b2eb01f43d09d9039128MD52TEXTSynergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms.pdf.txtSynergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms.pdf.txtExtracted texttext/plain1770https://www.arca.fiocruz.br/bitstream/icict/13549/3/Synergy%20of%20Omeprazole%20and%20Praziquantel%20In%20Vitro%20Treatment%20against%20Schistosoma%20mansoni%20Adult%20Worms.pdf.txt0a600ff94e108a2c8392f0f44e491e72MD53icict/135492019-06-19 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dc.title.pt_BR.fl_str_mv Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms
title Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms
spellingShingle Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms
Almeida, Giuliana Teixeira de
Schistosomiasis
S. mansoni
Praziquantel
enzyme E2
title_short Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms
title_full Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms
title_fullStr Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms
title_full_unstemmed Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms
title_sort Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms
author Almeida, Giuliana Teixeira de
author_facet Almeida, Giuliana Teixeira de
Lage, Regina Coeli Gonçalves
Anderson, Leticia
Venancio, Thiago Motta
Nakaya, Helder Takashi Imoto
Miyasato, Patrícia Aoki
Rofatto, Henrique Krambeck
Zerlotini, Adhemar
Nakano, Eliana
Oliveira, Guilherme Corrêa de
Almeida, Sergio Verjovski
author_role author
author2 Lage, Regina Coeli Gonçalves
Anderson, Leticia
Venancio, Thiago Motta
Nakaya, Helder Takashi Imoto
Miyasato, Patrícia Aoki
Rofatto, Henrique Krambeck
Zerlotini, Adhemar
Nakano, Eliana
Oliveira, Guilherme Corrêa de
Almeida, Sergio Verjovski
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Almeida, Giuliana Teixeira de
Lage, Regina Coeli Gonçalves
Anderson, Leticia
Venancio, Thiago Motta
Nakaya, Helder Takashi Imoto
Miyasato, Patrícia Aoki
Rofatto, Henrique Krambeck
Zerlotini, Adhemar
Nakano, Eliana
Oliveira, Guilherme Corrêa de
Almeida, Sergio Verjovski
dc.subject.en.pt_BR.fl_str_mv Schistosomiasis
S. mansoni
Praziquantel
enzyme E2
topic Schistosomiasis
S. mansoni
Praziquantel
enzyme E2
description Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil
publishDate 2015
dc.date.issued.fl_str_mv 2015
dc.date.accessioned.fl_str_mv 2016-04-05T19:03:07Z
dc.date.available.fl_str_mv 2016-04-05T19:03:07Z
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.citation.fl_str_mv ALMEIDA, Giuliana Teixeira de et al. Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms. PLoS Negl Trop Dis., vol. 9, n. 9, art. e0004086, 2015.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/13549
dc.identifier.issn.none.fl_str_mv 1935-2735
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pntd.0004086
identifier_str_mv ALMEIDA, Giuliana Teixeira de et al. Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms. PLoS Negl Trop Dis., vol. 9, n. 9, art. e0004086, 2015.
1935-2735
10.1371/journal.pntd.0004086
url https://www.arca.fiocruz.br/handle/icict/13549
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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