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dc.contributor.author Sülsen, Valeria Patricia
dc.contributor.author Puente, Vanesa Rocío
dc.contributor.author Papademetrio, Daniela Laura
dc.contributor.author Batlle, Alcira María del C.
dc.contributor.author Martino, Virginia Susana
dc.contributor.author Frank, Fernanda María
dc.contributor.author Lombardo, Maria Elisa
dc.date.available 2018-03-19T21:10:30Z
dc.date.issued 2016-03
dc.identifier.citation Sülsen, Valeria Patricia; Puente, Vanesa Rocío; Papademetrio, Daniela Laura; Batlle, Alcira María del C.; Martino, Virginia Susana; et al.; Mode of action of the sesquiterpene lactones psilostachyin and psilostachyin C on trypanosoma cruzi; Public Library of Science; Plos One; 11; 3; 3-2016; 1-14; e0150526
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/11336/39302
dc.description.abstract Trypanosoma cruzi is the causative agent of Chagas' disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzi-pain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its antiparasitic effect by interacting with hemin, while psilostachyin C interfered with sterol synthesis.
dc.format application/pdf
dc.language.iso eng
dc.publisher Public Library of Science
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject Trypanosoma cruzi
dc.subject Sesquiterpene lactona
dc.subject Psilostachyin
dc.subject Psilostachyin C
dc.subject.classification Salud Ocupacional
dc.subject.classification Ciencias de la Salud
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Mode of action of the sesquiterpene lactones psilostachyin and psilostachyin C on trypanosoma cruzi
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2018-03-15T14:06:34Z
dc.journal.volume 11
dc.journal.number 3
dc.journal.pagination 1-14; e0150526
dc.journal.pais Estados Unidos
dc.journal.ciudad San Francisco
dc.description.fil Fil: Sülsen, Valeria Patricia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Química y Metabolismo del Fármaco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Puente, Vanesa Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina
dc.description.fil Fil: Papademetrio, Daniela Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Batlle, Alcira María del C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina
dc.description.fil Fil: Martino, Virginia Susana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Química y Metabolismo del Fármaco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil Fil: Frank, Fernanda María. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
dc.description.fil Fil: Lombardo, Maria Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.journal.title Plos One
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0150526
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150526
dc.conicet.fuente unificacion


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  • Articulos(IQUIMEFA) [159]
    Articulos de INST.QUIMICA Y METABOLISMO DEL FARMACO (I)
  • Articulos(CIPYP) [35]
    Articulos de CENTRO DE INVEST. SOBRE PORFIRINAS Y PORFIRIAS
  • Articulos(IMPAM) [185]
    Articulos de INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA

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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)