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dc.contributor.author
Sülsen, Valeria Patricia
dc.contributor.author
Puente, Vanesa Rocío
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Papademetrio, Daniela Laura
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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
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Psilostachyin
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Psilostachyin C
dc.subject.classification
Salud Ocupacional
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Ciencias de la Salud
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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


Archivos asociados

 

Comunidades y colecciones

  • Articulos(IQUIMEFA) [170]
    Articulos de INST.QUIMICA Y METABOLISMO DEL FARMACO (I)
  • Articulos(CIPYP) [37]
    Articulos de CENTRO DE INVEST. SOBRE PORFIRINAS Y PORFIRIAS
  • Articulos(IMPAM) [191]
    Articulos de INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA

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