Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols

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dc.contributor.authorSoares, Juliana B R Corrêaen_ZA
dc.contributor.authorMenezes, Diegoen_ZA
dc.contributor.authorVannier-Santos, Marcos Aen_ZA
dc.contributor.authorFerreira-Pereira, Antonioen_ZA
dc.contributor.authorAlmeida, Giulliana Ten_ZA
dc.contributor.authorVenancio, Thiago Men_ZA
dc.contributor.authorVerjovski-Almeida, Sergioen_ZA
dc.contributor.authorZishiri, Vincent Ken_ZA
dc.contributor.authorKuter, Daviden_ZA
dc.contributor.authorHunter, Rogeren_ZA
dc.date.accessioned2015-11-23T12:39:05Z
dc.date.available2015-11-23T12:39:05Z
dc.date.issued2009en_ZA
dc.description.abstractAuthor Summary Heme is an essential molecule to most living organisms, but once in a free state it exerts toxic effects. Blood-feeding organisms evolved efficient ways to detoxify free heme derived from hemoglobin digestion. A key mechanism present in some hematophagous organisms consists of the crystallization of heme into a pigment named hemozoin. Schistosoma mansoni is one of the etiologic agents of human schistosomiasis, a parasitic disease that affects over 200 million people in tropical and subtropical areas. Hemozoin formation represents the main heme detoxification pathway in S. mansoni . Here, we report that the antimalarial quinoline methanols quinine and quinidine exert schistosomicidal effects notably due to their capacity to interfere with hemozoin formation. When quinine or quinidine were administered intraperitoneally during seven days to S. mansoni -infected mice (75 mg/kg/day), both worm and eggs burden were significantly reduced. Interestingly, hemozoin content in female worms was drastically affected after treatment with either compound. We also found that quinine caused important changes in the cellular organization of worm gastrodermis and increased expression of genes related to musculature, protein synthesis and repair mechanisms. Together, our results indicate that interference with hemozoin formation is a valid chemotherapeutic target for development of new schistosomicidal agents.en_ZA
dc.identifier.apacitationSoares, J. B. R. C., Menezes, D., Vannier-Santos, M. A., Ferreira-Pereira, A., Almeida, G. T., Venancio, T. M., ... Hunter, R. (2009). Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. <i>PLOS Neglected Tropical Diseases</i>, http://hdl.handle.net/11427/15366en_ZA
dc.identifier.chicagocitationSoares, Juliana B R Corrêa, Diego Menezes, Marcos A Vannier-Santos, Antonio Ferreira-Pereira, Giulliana T Almeida, Thiago M Venancio, Sergio Verjovski-Almeida, Vincent K Zishiri, David Kuter, and Roger Hunter "Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols." <i>PLOS Neglected Tropical Diseases</i> (2009) http://hdl.handle.net/11427/15366en_ZA
dc.identifier.citationSoares, J. C., Menezes, D., Vannier-Santos, M. A., Ferreira-Pereira, A., Almeida, G. T., Venancio, T. M., ... & Oliveira, M. F. (2009). Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. PLoS Negl Trop Dis, 3(7), e477. doi:10.1371/journal.pntd.0000477en_ZA
dc.identifier.ris TY - Journal Article AU - Soares, Juliana B R Corrêa AU - Menezes, Diego AU - Vannier-Santos, Marcos A AU - Ferreira-Pereira, Antonio AU - Almeida, Giulliana T AU - Venancio, Thiago M AU - Verjovski-Almeida, Sergio AU - Zishiri, Vincent K AU - Kuter, David AU - Hunter, Roger AB - Author Summary Heme is an essential molecule to most living organisms, but once in a free state it exerts toxic effects. Blood-feeding organisms evolved efficient ways to detoxify free heme derived from hemoglobin digestion. A key mechanism present in some hematophagous organisms consists of the crystallization of heme into a pigment named hemozoin. Schistosoma mansoni is one of the etiologic agents of human schistosomiasis, a parasitic disease that affects over 200 million people in tropical and subtropical areas. Hemozoin formation represents the main heme detoxification pathway in S. mansoni . Here, we report that the antimalarial quinoline methanols quinine and quinidine exert schistosomicidal effects notably due to their capacity to interfere with hemozoin formation. When quinine or quinidine were administered intraperitoneally during seven days to S. mansoni -infected mice (75 mg/kg/day), both worm and eggs burden were significantly reduced. Interestingly, hemozoin content in female worms was drastically affected after treatment with either compound. We also found that quinine caused important changes in the cellular organization of worm gastrodermis and increased expression of genes related to musculature, protein synthesis and repair mechanisms. Together, our results indicate that interference with hemozoin formation is a valid chemotherapeutic target for development of new schistosomicidal agents. DA - 2009 DB - OpenUCT DO - 10.1371/journal.pntd.0000477 DP - University of Cape Town J1 - PLOS Neglected Tropical Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols TI - Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols UR - http://hdl.handle.net/11427/15366 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15366
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pntd.0000477
dc.identifier.vancouvercitationSoares JBRC, Menezes D, Vannier-Santos MA, Ferreira-Pereira A, Almeida GT, Venancio TM, et al. Interference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanols. PLOS Neglected Tropical Diseases. 2009; http://hdl.handle.net/11427/15366.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2009 Corrêa Soares et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLOS Neglected Tropical Diseasesen_ZA
dc.source.urihttp://journals.plos.org/plosntdsen_ZA
dc.subject.otherSchistosoma mansonien_ZA
dc.subject.otherHemeen_ZA
dc.subject.otherQuinolinesen_ZA
dc.subject.otherCrystallizationen_ZA
dc.subject.otherAntimalarialsen_ZA
dc.subject.otherMethanolen_ZA
dc.subject.otherQuinineen_ZA
dc.subject.otherSchistosomiasisen_ZA
dc.titleInterference with hemozoin formation represents an important mechanism of schistosomicidal action of antimalarial quinoline methanolsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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