In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus

Autores
Nicolao, María Celeste; Elissondo, María Celina; Denegri, Guillermo Maria; Goya, Alejandra Beatriz; Cumino, Andrea Carina
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.
Fil: Nicolao, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina
Fil: Elissondo, María Celina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina
Fil: Denegri, Guillermo Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina
Fil: Goya, Alejandra Beatriz. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina
Fil: Cumino, Andrea Carina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina
Materia
Echinococcus Garnulosus
Hidatidosis
Echinococcosis Quística
Tamoxifen
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:11336/34879
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/34879
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosusNicolao, María CelesteElissondo, María CelinaDenegri, Guillermo MariaGoya, Alejandra BeatrizCumino, Andrea CarinaEchinococcus GarnulosusHidatidosisEchinococcosis QuísticaTamoxifenhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.Fil: Nicolao, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; ArgentinaFil: Elissondo, María Celina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; ArgentinaFil: Denegri, Guillermo Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; ArgentinaFil: Goya, Alejandra Beatriz. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; ArgentinaFil: Cumino, Andrea Carina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; ArgentinaAmerican Society for Microbiology2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/34879Nicolao, María Celeste; Elissondo, María Celina; Denegri, Guillermo Maria; Goya, Alejandra Beatriz; Cumino, Andrea Carina; In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 58; 9; 9-2014; 5146-51540066-4804CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.02113-13info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/58/9/5146info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:56:10Zoai:ri.conicet.gov.ar:11336/34879instacron: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 09:56:10.604CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
title In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
spellingShingle In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
Nicolao, María Celeste
Echinococcus Garnulosus
Hidatidosis
Echinococcosis Quística
Tamoxifen
title_short In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
title_full In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
title_fullStr In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
title_full_unstemmed In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
title_sort In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus
dc.creator.none.fl_str_mv Nicolao, María Celeste
Elissondo, María Celina
Denegri, Guillermo Maria
Goya, Alejandra Beatriz
Cumino, Andrea Carina
author Nicolao, María Celeste
author_facet Nicolao, María Celeste
Elissondo, María Celina
Denegri, Guillermo Maria
Goya, Alejandra Beatriz
Cumino, Andrea Carina
author_role author
author2 Elissondo, María Celina
Denegri, Guillermo Maria
Goya, Alejandra Beatriz
Cumino, Andrea Carina
author2_role author
author
author
author
dc.subject.none.fl_str_mv Echinococcus Garnulosus
Hidatidosis
Echinococcosis Quística
Tamoxifen
topic Echinococcus Garnulosus
Hidatidosis
Echinococcosis Quística
Tamoxifen
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.
Fil: Nicolao, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina
Fil: Elissondo, María Celina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina
Fil: Denegri, Guillermo Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina
Fil: Goya, Alejandra Beatriz. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina
Fil: Cumino, Andrea Carina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina
description Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.
publishDate 2014
dc.date.none.fl_str_mv 2014-09
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/11336/34879
Nicolao, María Celeste; Elissondo, María Celina; Denegri, Guillermo Maria; Goya, Alejandra Beatriz; Cumino, Andrea Carina; In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 58; 9; 9-2014; 5146-5154
0066-4804
CONICET Digital
CONICET
url http://hdl.handle.net/11336/34879
identifier_str_mv Nicolao, María Celeste; Elissondo, María Celina; Denegri, Guillermo Maria; Goya, Alejandra Beatriz; Cumino, Andrea Carina; In Vitro and In Vivo Effects of Tamoxifen against Larval Stage Echinococcus granulosus; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 58; 9; 9-2014; 5146-5154
0066-4804
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.02113-13
info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/58/9/5146
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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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score 13.070432

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