Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2009 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/9997 |
Resumo: | Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laborato´rio de Bioquı´mica Redox, Programa de Biologia Molecular e Biotecnologia. Rio de Janeiro, RJ, Brasil |
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Soares, Juliana Baptista Rocha CorrêaMenezes, Diego SilvaSantos, Marcos André Vannier dosPereira, Antonio FerreiraAlmeida, Giulliana Tessarin eVenancio, Thiago MottaAlmeida, Sergio VerjovskiZishiri, Vincent KKuter, DavidHunter, RogerEgan, Timothy JOliveira, Marcus Fernandes de2015-04-15T12:07:27Z2015-04-15T12:07:27Z2009SOARES, J. B. R. C. et al. Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. PLoS Neglected Tropical Diseases, v. 3, n. 7, p. e477, 2009.1935-2735https://www.arca.fiocruz.br/handle/icict/999710.1371/journal.pntd.0000477engSan Francisco, CA Public Library of ScienceAnti-HelmínticoSchistosoma mansoniAnti-HelmínticosHemeproteínasQuinacrinaQuinidinaQuininaSchistosoma mansoniCamundongosInterference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanolsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laborato´rio de Bioquı´mica Redox, Programa de Biologia Molecular e Biotecnologia. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia Prof. Paulo de Goes. 3 Departamento de Microbiologia Geral. Rio de Janeiro, RJ, 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, BrasilUniversity of Cape Town. Department of Chemistry. Rondebosch, Cape Town, South AfricaUniversity of Cape Town. Department of Chemistry. Rondebosch, Cape Town, South AfricaUniversity of Cape Town. Department of Chemistry. Rondebosch, Cape Town, South AfricaUniversity of Cape Town. Department of Chemistry. Rondebosch, Cape Town, South AfricaUniversidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laborato´rio de Bioquı´mica Redox, Programa de Biologia Molecular e Biotecnologia. Rio de Janeiro, RJ, BrasilBackground: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel remains the main drug used for schistosomiasis treatment, and reliance on the single therapy has been prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within the S. mansoni gut is a major heme detoxification route with lipid droplets involved in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of three antimalarial compounds, quinine (QN), quinidine (QND) and quinacrine (QCR) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN, and QND (75 mg/kg/day) from the 11th to 17th day after infection caused significant decreases in worm burden (39%–61%) and egg production (42%–98%). Hz formation was significantly inhibited (40%–65%) in female worms recovered from QN- and QND-treated mice and correlated with reduction in the female worm burden. We also observed that QN treatment promoted remarkable ultrastructural changes in male and female worms, particularly in the gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in the liver. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by the antimalarial quinoline methanols indicates that interference with Hz formation in S. mansoni represents an important mechanism of schistosomicidal action of these compounds and points out the heme crystallization process as a valid chemotherapeutic target to treat schistosomiasis.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82352https://www.arca.fiocruz.br/bitstream/icict/9997/1/license.txtafbdf7d7a9bcf771a1cc7edf5f618413MD51ORIGINALSoares JBC Interference with hemozin.pdfSoares JBC Interference with hemozin.pdfapplication/pdf591172https://www.arca.fiocruz.br/bitstream/icict/9997/2/Soares%20JBC%20Interference%20with%20hemozin.pdfebc535d502d25e178e31566869138037MD52TEXTSoares JBC Interference with hemozin.pdf.txtSoares JBC Interference with hemozin.pdf.txtExtracted texttext/plain88834https://www.arca.fiocruz.br/bitstream/icict/9997/3/Soares%20JBC%20Interference%20with%20hemozin.pdf.txt8e8a608d1ada80d7164bfce4bc5d7d43MD53icict/99972023-03-15 14:33:21.04oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:21Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols |
| title |
Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols |
| spellingShingle |
Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols Soares, Juliana Baptista Rocha Corrêa Anti-Helmíntico Schistosoma mansoni Anti-Helmínticos Hemeproteínas Quinacrina Quinidina Quinina Schistosoma mansoni Camundongos |
| title_short |
Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols |
| title_full |
Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols |
| title_fullStr |
Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols |
| title_full_unstemmed |
Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols |
| title_sort |
Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols |
| author |
Soares, Juliana Baptista Rocha Corrêa |
| author_facet |
Soares, Juliana Baptista Rocha Corrêa Menezes, Diego Silva Santos, Marcos André Vannier dos Pereira, Antonio Ferreira Almeida, Giulliana Tessarin e Venancio, Thiago Motta Almeida, Sergio Verjovski Zishiri, Vincent K Kuter, David Hunter, Roger Egan, Timothy J Oliveira, Marcus Fernandes de |
| author_role |
author |
| author2 |
Menezes, Diego Silva Santos, Marcos André Vannier dos Pereira, Antonio Ferreira Almeida, Giulliana Tessarin e Venancio, Thiago Motta Almeida, Sergio Verjovski Zishiri, Vincent K Kuter, David Hunter, Roger Egan, Timothy J Oliveira, Marcus Fernandes de |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Soares, Juliana Baptista Rocha Corrêa Menezes, Diego Silva Santos, Marcos André Vannier dos Pereira, Antonio Ferreira Almeida, Giulliana Tessarin e Venancio, Thiago Motta Almeida, Sergio Verjovski Zishiri, Vincent K Kuter, David Hunter, Roger Egan, Timothy J Oliveira, Marcus Fernandes de |
| dc.subject.other.pt_BR.fl_str_mv |
Anti-Helmíntico Schistosoma mansoni |
| topic |
Anti-Helmíntico Schistosoma mansoni Anti-Helmínticos Hemeproteínas Quinacrina Quinidina Quinina Schistosoma mansoni Camundongos |
| dc.subject.decs.pt_BR.fl_str_mv |
Anti-Helmínticos Hemeproteínas Quinacrina Quinidina Quinina Schistosoma mansoni Camundongos |
| description |
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laborato´rio de Bioquı´mica Redox, Programa de Biologia Molecular e Biotecnologia. Rio de Janeiro, RJ, Brasil |
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2009 |
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2009 |
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2015-04-15T12:07:27Z |
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2015-04-15T12:07:27Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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SOARES, J. B. R. C. et al. Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. PLoS Neglected Tropical Diseases, v. 3, n. 7, p. e477, 2009. |
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https://www.arca.fiocruz.br/handle/icict/9997 |
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1935-2735 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pntd.0000477 |
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SOARES, J. B. R. C. et al. Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. PLoS Neglected Tropical Diseases, v. 3, n. 7, p. e477, 2009. 1935-2735 10.1371/journal.pntd.0000477 |
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