Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease

Autores
Lo Presti, Maria Silvina; Bazán, Paola Carolina; Strauss, Mariana; Báez, Alejandra L.; Rivarola, Héctor Walter; Pagliani Oliva, Patricia A.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Thioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent phenothiazines to inhibit trypanothione reductase irreversibly. Trypanothione reductase is an essential enzyme for the survival of Trypanosoma cruzi in the host. Here, we reviewed the use of this drug for the treatment of T. cruzi experimental infection. In our laboratory, we have studied the effect of TDZ for the treatment of mice infected with different strains of T. cruzi and treated in the acute or in the chronic phases of the experimental infection, using two different schedules: TDZ at a dose of 80 mg/kg/day, for 3 days starting 1 h after infection (acute phase), or TDZ 80 mg/kg/day for 12 days starting 180 days post infection (d.p.i.) (chronic phase). In our experience, the treatment of infected mice, in the acute or in the chronic phases of the infection, with TDZ led to a large reduction in the mortality rates and in the cardiac histological and electrocardiographical abnormalities, and modified the natural evolution of the experimental infection. These analyses reinforce the importance of treatment in the chronic phase to decrease, retard or stop the evolution to chagasic myocardiopathy. Other evidence leading to the use of this drug as a potential chemotherapeutic agent for Chagas disease treatment is also revised.
Fil: Lo Presti, Maria Silvina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Bazán, Paola Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Strauss, Mariana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Báez, Alejandra L.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Rivarola, Héctor Walter. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Pagliani Oliva, Patricia A.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Favaloro. Facultad de Medicina; Argentina
Materia
Tioridazine
Trypanotione Reductase
Chagas Disease Chemotherapy
Trypanosoma Cruzi Strains
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/11362
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/11362
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas diseaseLo Presti, Maria SilvinaBazán, Paola CarolinaStrauss, MarianaBáez, Alejandra L.Rivarola, Héctor WalterPagliani Oliva, Patricia A.TioridazineTrypanotione ReductaseChagas Disease ChemotherapyTrypanosoma Cruzi Strainshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Thioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent phenothiazines to inhibit trypanothione reductase irreversibly. Trypanothione reductase is an essential enzyme for the survival of Trypanosoma cruzi in the host. Here, we reviewed the use of this drug for the treatment of T. cruzi experimental infection. In our laboratory, we have studied the effect of TDZ for the treatment of mice infected with different strains of T. cruzi and treated in the acute or in the chronic phases of the experimental infection, using two different schedules: TDZ at a dose of 80 mg/kg/day, for 3 days starting 1 h after infection (acute phase), or TDZ 80 mg/kg/day for 12 days starting 180 days post infection (d.p.i.) (chronic phase). In our experience, the treatment of infected mice, in the acute or in the chronic phases of the infection, with TDZ led to a large reduction in the mortality rates and in the cardiac histological and electrocardiographical abnormalities, and modified the natural evolution of the experimental infection. These analyses reinforce the importance of treatment in the chronic phase to decrease, retard or stop the evolution to chagasic myocardiopathy. Other evidence leading to the use of this drug as a potential chemotherapeutic agent for Chagas disease treatment is also revised.Fil: Lo Presti, Maria Silvina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; ArgentinaFil: Bazán, Paola Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; ArgentinaFil: Strauss, Mariana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; ArgentinaFil: Báez, Alejandra L.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; ArgentinaFil: Rivarola, Héctor Walter. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; ArgentinaFil: Pagliani Oliva, Patricia A.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Favaloro. Facultad de Medicina; ArgentinaElsevier Science2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/11362Lo Presti, Maria Silvina; Bazán, Paola Carolina; Strauss, Mariana; Báez, Alejandra L.; Rivarola, Héctor Walter; et al.; Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease; Elsevier Science; Acta Tropica; 145; 5-2015; 79-870001-706Xenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.actatropica.2015.02.012info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0001706X15000327info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:00:59Zoai:ri.conicet.gov.ar:11336/11362instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:00:59.231CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease
title Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease
spellingShingle Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease
Lo Presti, Maria Silvina
Tioridazine
Trypanotione Reductase
Chagas Disease Chemotherapy
Trypanosoma Cruzi Strains
title_short Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease
title_full Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease
title_fullStr Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease
title_full_unstemmed Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease
title_sort Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease
dc.creator.none.fl_str_mv Lo Presti, Maria Silvina
Bazán, Paola Carolina
Strauss, Mariana
Báez, Alejandra L.
Rivarola, Héctor Walter
Pagliani Oliva, Patricia A.
author Lo Presti, Maria Silvina
author_facet Lo Presti, Maria Silvina
Bazán, Paola Carolina
Strauss, Mariana
Báez, Alejandra L.
Rivarola, Héctor Walter
Pagliani Oliva, Patricia A.
author_role author
author2 Bazán, Paola Carolina
Strauss, Mariana
Báez, Alejandra L.
Rivarola, Héctor Walter
Pagliani Oliva, Patricia A.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Tioridazine
Trypanotione Reductase
Chagas Disease Chemotherapy
Trypanosoma Cruzi Strains
topic Tioridazine
Trypanotione Reductase
Chagas Disease Chemotherapy
Trypanosoma Cruzi Strains
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Thioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent phenothiazines to inhibit trypanothione reductase irreversibly. Trypanothione reductase is an essential enzyme for the survival of Trypanosoma cruzi in the host. Here, we reviewed the use of this drug for the treatment of T. cruzi experimental infection. In our laboratory, we have studied the effect of TDZ for the treatment of mice infected with different strains of T. cruzi and treated in the acute or in the chronic phases of the experimental infection, using two different schedules: TDZ at a dose of 80 mg/kg/day, for 3 days starting 1 h after infection (acute phase), or TDZ 80 mg/kg/day for 12 days starting 180 days post infection (d.p.i.) (chronic phase). In our experience, the treatment of infected mice, in the acute or in the chronic phases of the infection, with TDZ led to a large reduction in the mortality rates and in the cardiac histological and electrocardiographical abnormalities, and modified the natural evolution of the experimental infection. These analyses reinforce the importance of treatment in the chronic phase to decrease, retard or stop the evolution to chagasic myocardiopathy. Other evidence leading to the use of this drug as a potential chemotherapeutic agent for Chagas disease treatment is also revised.
Fil: Lo Presti, Maria Silvina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Bazán, Paola Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Strauss, Mariana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Báez, Alejandra L.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Rivarola, Héctor Walter. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina
Fil: Pagliani Oliva, Patricia A.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Favaloro. Facultad de Medicina; Argentina
description Thioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent phenothiazines to inhibit trypanothione reductase irreversibly. Trypanothione reductase is an essential enzyme for the survival of Trypanosoma cruzi in the host. Here, we reviewed the use of this drug for the treatment of T. cruzi experimental infection. In our laboratory, we have studied the effect of TDZ for the treatment of mice infected with different strains of T. cruzi and treated in the acute or in the chronic phases of the experimental infection, using two different schedules: TDZ at a dose of 80 mg/kg/day, for 3 days starting 1 h after infection (acute phase), or TDZ 80 mg/kg/day for 12 days starting 180 days post infection (d.p.i.) (chronic phase). In our experience, the treatment of infected mice, in the acute or in the chronic phases of the infection, with TDZ led to a large reduction in the mortality rates and in the cardiac histological and electrocardiographical abnormalities, and modified the natural evolution of the experimental infection. These analyses reinforce the importance of treatment in the chronic phase to decrease, retard or stop the evolution to chagasic myocardiopathy. Other evidence leading to the use of this drug as a potential chemotherapeutic agent for Chagas disease treatment is also revised.
publishDate 2015
dc.date.none.fl_str_mv 2015-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/11362
Lo Presti, Maria Silvina; Bazán, Paola Carolina; Strauss, Mariana; Báez, Alejandra L.; Rivarola, Héctor Walter; et al.; Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease; Elsevier Science; Acta Tropica; 145; 5-2015; 79-87
0001-706X
url http://hdl.handle.net/11336/11362
identifier_str_mv Lo Presti, Maria Silvina; Bazán, Paola Carolina; Strauss, Mariana; Báez, Alejandra L.; Rivarola, Héctor Walter; et al.; Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease; Elsevier Science; Acta Tropica; 145; 5-2015; 79-87
0001-706X
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.actatropica.2015.02.012
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0001706X15000327
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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