Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses

Autores
Loos, Julia Alexandra; Franco, Micaela; Chop, Maia; Rodríguez Rodrígues, Christian Fernando Ariel; Cumino, Andrea Carina
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In an attempt to find new anti-echinococcal drugs, resveratrol (Rsv) effectiveness against the larval stages of Echinococcus granulosus and E. multilocularis was evaluated. The in vitro effect of Rsv on parasites was assessed via optical and electron microscopy, RT-qPCR and immunohistochemistry. In vivo efficacy was evaluated in murine models of cystic (CE) and alveolar echinococcosis (AE). The impact of infection and drug treatment on the mouse bone marrow hematopoietic stem cell (HSC) population and its differentiation into dendritic cells (BMDCs) was investigated via flow cytometry and RT-qPCR. In vitro treatment with Rsv reduced E. granulosus metacestode and protoscolex viability in a concentration-dependent manner, caused ultrastructural damage, increased autophagy gene transcription, and raised Eg-Atg8 expression while suppressing Eg-TOR. However, the intraperitoneal administration of Rsv was not only ineffective, but also promoted parasite development in mice with CE and AE. In the early infection model of AE treated with Rsv, an expansion of HSCs was observed followed by their differentiation towards BMCDs. The latter showed an anti-inflammatory phenotype and reduced LPS-stimulated activation compared to control BMDCs. We suggest that Rsv ineffectiveness could have been caused by the low intracystic concentration achieved in vivo and the drug’s hormetic effect, with opposite anti-parasitic and immunomodulatory responses in different doses.
Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Franco, Micaela. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Dr. Oscar Alende de Mar del Plata.; Argentina
Fil: Chop, Maia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina
Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Materia
Echinococcus granulosus
resveratrol
BMDCs
anti-parasitic response
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/222411
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/222411
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo ResponsesLoos, Julia AlexandraFranco, MicaelaChop, MaiaRodríguez Rodrígues, Christian Fernando ArielCumino, Andrea CarinaEchinococcus granulosusresveratrolBMDCsanti-parasitic responsehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In an attempt to find new anti-echinococcal drugs, resveratrol (Rsv) effectiveness against the larval stages of Echinococcus granulosus and E. multilocularis was evaluated. The in vitro effect of Rsv on parasites was assessed via optical and electron microscopy, RT-qPCR and immunohistochemistry. In vivo efficacy was evaluated in murine models of cystic (CE) and alveolar echinococcosis (AE). The impact of infection and drug treatment on the mouse bone marrow hematopoietic stem cell (HSC) population and its differentiation into dendritic cells (BMDCs) was investigated via flow cytometry and RT-qPCR. In vitro treatment with Rsv reduced E. granulosus metacestode and protoscolex viability in a concentration-dependent manner, caused ultrastructural damage, increased autophagy gene transcription, and raised Eg-Atg8 expression while suppressing Eg-TOR. However, the intraperitoneal administration of Rsv was not only ineffective, but also promoted parasite development in mice with CE and AE. In the early infection model of AE treated with Rsv, an expansion of HSCs was observed followed by their differentiation towards BMCDs. The latter showed an anti-inflammatory phenotype and reduced LPS-stimulated activation compared to control BMDCs. We suggest that Rsv ineffectiveness could have been caused by the low intracystic concentration achieved in vivo and the drug’s hormetic effect, with opposite anti-parasitic and immunomodulatory responses in different doses.Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Franco, Micaela. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Dr. Oscar Alende de Mar del Plata.; ArgentinaFil: Chop, Maia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaMDPI2023-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/222411Loos, Julia Alexandra; Franco, Micaela; Chop, Maia; Rodríguez Rodrígues, Christian Fernando Ariel; Cumino, Andrea Carina; Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses; MDPI; Tropical Medicine and Infectious Disease; 8; 10; 9-2023; 1-182414-6366CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2414-6366/8/10/460info:eu-repo/semantics/altIdentifier/doi/10.3390/tropicalmed8100460info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:23:44Zoai:ri.conicet.gov.ar:11336/222411instacron: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 10:23:44.319CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses
title Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses
spellingShingle Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses
Loos, Julia Alexandra
Echinococcus granulosus
resveratrol
BMDCs
anti-parasitic response
title_short Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses
title_full Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses
title_fullStr Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses
title_full_unstemmed Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses
title_sort Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses
dc.creator.none.fl_str_mv Loos, Julia Alexandra
Franco, Micaela
Chop, Maia
Rodríguez Rodrígues, Christian Fernando Ariel
Cumino, Andrea Carina
author Loos, Julia Alexandra
author_facet Loos, Julia Alexandra
Franco, Micaela
Chop, Maia
Rodríguez Rodrígues, Christian Fernando Ariel
Cumino, Andrea Carina
author_role author
author2 Franco, Micaela
Chop, Maia
Rodríguez Rodrígues, Christian Fernando Ariel
Cumino, Andrea Carina
author2_role author
author
author
author
dc.subject.none.fl_str_mv Echinococcus granulosus
resveratrol
BMDCs
anti-parasitic response
topic Echinococcus granulosus
resveratrol
BMDCs
anti-parasitic response
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In an attempt to find new anti-echinococcal drugs, resveratrol (Rsv) effectiveness against the larval stages of Echinococcus granulosus and E. multilocularis was evaluated. The in vitro effect of Rsv on parasites was assessed via optical and electron microscopy, RT-qPCR and immunohistochemistry. In vivo efficacy was evaluated in murine models of cystic (CE) and alveolar echinococcosis (AE). The impact of infection and drug treatment on the mouse bone marrow hematopoietic stem cell (HSC) population and its differentiation into dendritic cells (BMDCs) was investigated via flow cytometry and RT-qPCR. In vitro treatment with Rsv reduced E. granulosus metacestode and protoscolex viability in a concentration-dependent manner, caused ultrastructural damage, increased autophagy gene transcription, and raised Eg-Atg8 expression while suppressing Eg-TOR. However, the intraperitoneal administration of Rsv was not only ineffective, but also promoted parasite development in mice with CE and AE. In the early infection model of AE treated with Rsv, an expansion of HSCs was observed followed by their differentiation towards BMCDs. The latter showed an anti-inflammatory phenotype and reduced LPS-stimulated activation compared to control BMDCs. We suggest that Rsv ineffectiveness could have been caused by the low intracystic concentration achieved in vivo and the drug’s hormetic effect, with opposite anti-parasitic and immunomodulatory responses in different doses.
Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Franco, Micaela. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Dr. Oscar Alende de Mar del Plata.; Argentina
Fil: Chop, Maia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina
Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
description In an attempt to find new anti-echinococcal drugs, resveratrol (Rsv) effectiveness against the larval stages of Echinococcus granulosus and E. multilocularis was evaluated. The in vitro effect of Rsv on parasites was assessed via optical and electron microscopy, RT-qPCR and immunohistochemistry. In vivo efficacy was evaluated in murine models of cystic (CE) and alveolar echinococcosis (AE). The impact of infection and drug treatment on the mouse bone marrow hematopoietic stem cell (HSC) population and its differentiation into dendritic cells (BMDCs) was investigated via flow cytometry and RT-qPCR. In vitro treatment with Rsv reduced E. granulosus metacestode and protoscolex viability in a concentration-dependent manner, caused ultrastructural damage, increased autophagy gene transcription, and raised Eg-Atg8 expression while suppressing Eg-TOR. However, the intraperitoneal administration of Rsv was not only ineffective, but also promoted parasite development in mice with CE and AE. In the early infection model of AE treated with Rsv, an expansion of HSCs was observed followed by their differentiation towards BMCDs. The latter showed an anti-inflammatory phenotype and reduced LPS-stimulated activation compared to control BMDCs. We suggest that Rsv ineffectiveness could have been caused by the low intracystic concentration achieved in vivo and the drug’s hormetic effect, with opposite anti-parasitic and immunomodulatory responses in different doses.
publishDate 2023
dc.date.none.fl_str_mv 2023-09
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/11336/222411
Loos, Julia Alexandra; Franco, Micaela; Chop, Maia; Rodríguez Rodrígues, Christian Fernando Ariel; Cumino, Andrea Carina; Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses; MDPI; Tropical Medicine and Infectious Disease; 8; 10; 9-2023; 1-18
2414-6366
CONICET Digital
CONICET
url http://hdl.handle.net/11336/222411
identifier_str_mv Loos, Julia Alexandra; Franco, Micaela; Chop, Maia; Rodríguez Rodrígues, Christian Fernando Ariel; Cumino, Andrea Carina; Resveratrol against Echinococcus sp.: Discrepancies between In Vitro and In Vivo Responses; MDPI; Tropical Medicine and Infectious Disease; 8; 10; 9-2023; 1-18
2414-6366
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2414-6366/8/10/460
info:eu-repo/semantics/altIdentifier/doi/10.3390/tropicalmed8100460
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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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