Paradoxical pharmacology effect of resveratrol against Echinococcosis

Autores
Franco, Micaela; Loos, Julia Alexandra; Rivis, Rocio; Chop, Maia; Rodríguez Rodrígues, Christian Fernando Ariel; Cumino, Andrea Carina
Año de publicación
2023
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Resveratrol (Rsv) is a phytoalexin with antibacterial, anticancer and antiparasite properties. We analyzed for the first time the pharmacological effects of resveratrol (Rsv) on Echinococcus granulosus sensu lato complex and E. multilocularis. In vitro treatment with 50 and 100 μM Rsv reduced the viability of E. granulosus metacestodes and protoscoleces by at least 75% after 4 and 13 days, respectively. Rsv treatment caused deleterious ultrastructural effects in metacestodes, increased the transcription of autophagy genes, and raised Eg-Atg8 expression while suppresed Eg-TOR, leading to autophagy and parasite death. However, the intraperitoneal administration of Rsv (100 mg kg−1 day−1) was not only ineffective, but also promoted parasite development in mice with cystic and alveolar echinococcosis. We also showed in early alveolar echinococcosis treated with Rsv a hematopoietic stem cell expansion followed by their differentiation towards dendritic cells (BMCDs), with CD80, CD86 and MHCII induction. BMDCs from early stage of AE infection produce high gene expression levels of IL-6 and TGF-β, which could to determine T cell activation and polarization to Th17 subset, characteristic of the immune response during early infection phase. Contrarily, BMDCs from Rsv-treated AE mice inhibited-transcription of IL-6 (p<0.01), TNFα (p<0.05), TGFβ (p<0.05) and IL-10 (p<0.05), as well as it provoked a reduction of LPS-stimulated BMDC activation in comparison with control BMDCs, provoking an anti-inflammatory response in BMDCs from Rsv-treated mice. We suggest that Rsv ineffectiveness could be caused by the low intracystic concentration (≈ 30 ± 2 μM) achieved in vivo and the drug´s hormetic effect, which accounts for the opposite anti-parasitic and immodulatory responses at different doses. Therefore, our assays do not allow us to propose to the RSV as a drug for the treatment of CE neither AE, due to it was perhaps not delivered and accumulated in the parasite in optimal amounts.
Fil: Franco, Micaela. 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: 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: Rivis, Rocio. 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: 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
XXXIV Reunión Anual de Sociedad Argentina de Protozoología
La Plata
Argentina
Sociedad Argentina de Protozoología
Materia
Resveratrol
Echinococcus
Immune response
In vivo parasite development
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:11336/276695
Acceder
id CONICETDig_75ecdec101d289152a933962f4b0a3bb
oai_identifier_str oai:ri.conicet.gov.ar:11336/276695
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Paradoxical pharmacology effect of resveratrol against EchinococcosisFranco, MicaelaLoos, Julia AlexandraRivis, RocioChop, MaiaRodríguez Rodrígues, Christian Fernando ArielCumino, Andrea CarinaResveratrolEchinococcusImmune responseIn vivo parasite developmenthttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Resveratrol (Rsv) is a phytoalexin with antibacterial, anticancer and antiparasite properties. We analyzed for the first time the pharmacological effects of resveratrol (Rsv) on Echinococcus granulosus sensu lato complex and E. multilocularis. In vitro treatment with 50 and 100 μM Rsv reduced the viability of E. granulosus metacestodes and protoscoleces by at least 75% after 4 and 13 days, respectively. Rsv treatment caused deleterious ultrastructural effects in metacestodes, increased the transcription of autophagy genes, and raised Eg-Atg8 expression while suppresed Eg-TOR, leading to autophagy and parasite death. However, the intraperitoneal administration of Rsv (100 mg kg−1 day−1) was not only ineffective, but also promoted parasite development in mice with cystic and alveolar echinococcosis. We also showed in early alveolar echinococcosis treated with Rsv a hematopoietic stem cell expansion followed by their differentiation towards dendritic cells (BMCDs), with CD80, CD86 and MHCII induction. BMDCs from early stage of AE infection produce high gene expression levels of IL-6 and TGF-β, which could to determine T cell activation and polarization to Th17 subset, characteristic of the immune response during early infection phase. Contrarily, BMDCs from Rsv-treated AE mice inhibited-transcription of IL-6 (p<0.01), TNFα (p<0.05), TGFβ (p<0.05) and IL-10 (p<0.05), as well as it provoked a reduction of LPS-stimulated BMDC activation in comparison with control BMDCs, provoking an anti-inflammatory response in BMDCs from Rsv-treated mice. We suggest that Rsv ineffectiveness could be caused by the low intracystic concentration (≈ 30 ± 2 μM) achieved in vivo and the drug´s hormetic effect, which accounts for the opposite anti-parasitic and immodulatory responses at different doses. Therefore, our assays do not allow us to propose to the RSV as a drug for the treatment of CE neither AE, due to it was perhaps not delivered and accumulated in the parasite in optimal amounts.Fil: Franco, Micaela. 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: 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: Rivis, Rocio. 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: 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.; ArgentinaXXXIV Reunión Anual de Sociedad Argentina de ProtozoologíaLa PlataArgentinaSociedad Argentina de ProtozoologíaSociedad Argentina de Protozoología2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/276695Paradoxical pharmacology effect of resveratrol against Echinococcosis; XXXIV Reunión Anual de Sociedad Argentina de Protozoología; La Plata; Argentina; 2023; 60-602953-5751CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://protozoologia.org.ar/revista-parasitus/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-17T14:37:18Zoai:ri.conicet.gov.ar:11336/276695instacron: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:34982025-12-17 14:37:18.607CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Paradoxical pharmacology effect of resveratrol against Echinococcosis
title Paradoxical pharmacology effect of resveratrol against Echinococcosis
spellingShingle Paradoxical pharmacology effect of resveratrol against Echinococcosis
Franco, Micaela
Resveratrol
Echinococcus
Immune response
In vivo parasite development
title_short Paradoxical pharmacology effect of resveratrol against Echinococcosis
title_full Paradoxical pharmacology effect of resveratrol against Echinococcosis
title_fullStr Paradoxical pharmacology effect of resveratrol against Echinococcosis
title_full_unstemmed Paradoxical pharmacology effect of resveratrol against Echinococcosis
title_sort Paradoxical pharmacology effect of resveratrol against Echinococcosis
dc.creator.none.fl_str_mv Franco, Micaela
Loos, Julia Alexandra
Rivis, Rocio
Chop, Maia
Rodríguez Rodrígues, Christian Fernando Ariel
Cumino, Andrea Carina
author Franco, Micaela
author_facet Franco, Micaela
Loos, Julia Alexandra
Rivis, Rocio
Chop, Maia
Rodríguez Rodrígues, Christian Fernando Ariel
Cumino, Andrea Carina
author_role author
author2 Loos, Julia Alexandra
Rivis, Rocio
Chop, Maia
Rodríguez Rodrígues, Christian Fernando Ariel
Cumino, Andrea Carina
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Resveratrol
Echinococcus
Immune response
In vivo parasite development
topic Resveratrol
Echinococcus
Immune response
In vivo parasite development
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Resveratrol (Rsv) is a phytoalexin with antibacterial, anticancer and antiparasite properties. We analyzed for the first time the pharmacological effects of resveratrol (Rsv) on Echinococcus granulosus sensu lato complex and E. multilocularis. In vitro treatment with 50 and 100 μM Rsv reduced the viability of E. granulosus metacestodes and protoscoleces by at least 75% after 4 and 13 days, respectively. Rsv treatment caused deleterious ultrastructural effects in metacestodes, increased the transcription of autophagy genes, and raised Eg-Atg8 expression while suppresed Eg-TOR, leading to autophagy and parasite death. However, the intraperitoneal administration of Rsv (100 mg kg−1 day−1) was not only ineffective, but also promoted parasite development in mice with cystic and alveolar echinococcosis. We also showed in early alveolar echinococcosis treated with Rsv a hematopoietic stem cell expansion followed by their differentiation towards dendritic cells (BMCDs), with CD80, CD86 and MHCII induction. BMDCs from early stage of AE infection produce high gene expression levels of IL-6 and TGF-β, which could to determine T cell activation and polarization to Th17 subset, characteristic of the immune response during early infection phase. Contrarily, BMDCs from Rsv-treated AE mice inhibited-transcription of IL-6 (p<0.01), TNFα (p<0.05), TGFβ (p<0.05) and IL-10 (p<0.05), as well as it provoked a reduction of LPS-stimulated BMDC activation in comparison with control BMDCs, provoking an anti-inflammatory response in BMDCs from Rsv-treated mice. We suggest that Rsv ineffectiveness could be caused by the low intracystic concentration (≈ 30 ± 2 μM) achieved in vivo and the drug´s hormetic effect, which accounts for the opposite anti-parasitic and immodulatory responses at different doses. Therefore, our assays do not allow us to propose to the RSV as a drug for the treatment of CE neither AE, due to it was perhaps not delivered and accumulated in the parasite in optimal amounts.
Fil: Franco, Micaela. 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: 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: Rivis, Rocio. 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: 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
XXXIV Reunión Anual de Sociedad Argentina de Protozoología
La Plata
Argentina
Sociedad Argentina de Protozoología
description Resveratrol (Rsv) is a phytoalexin with antibacterial, anticancer and antiparasite properties. We analyzed for the first time the pharmacological effects of resveratrol (Rsv) on Echinococcus granulosus sensu lato complex and E. multilocularis. In vitro treatment with 50 and 100 μM Rsv reduced the viability of E. granulosus metacestodes and protoscoleces by at least 75% after 4 and 13 days, respectively. Rsv treatment caused deleterious ultrastructural effects in metacestodes, increased the transcription of autophagy genes, and raised Eg-Atg8 expression while suppresed Eg-TOR, leading to autophagy and parasite death. However, the intraperitoneal administration of Rsv (100 mg kg−1 day−1) was not only ineffective, but also promoted parasite development in mice with cystic and alveolar echinococcosis. We also showed in early alveolar echinococcosis treated with Rsv a hematopoietic stem cell expansion followed by their differentiation towards dendritic cells (BMCDs), with CD80, CD86 and MHCII induction. BMDCs from early stage of AE infection produce high gene expression levels of IL-6 and TGF-β, which could to determine T cell activation and polarization to Th17 subset, characteristic of the immune response during early infection phase. Contrarily, BMDCs from Rsv-treated AE mice inhibited-transcription of IL-6 (p<0.01), TNFα (p<0.05), TGFβ (p<0.05) and IL-10 (p<0.05), as well as it provoked a reduction of LPS-stimulated BMDC activation in comparison with control BMDCs, provoking an anti-inflammatory response in BMDCs from Rsv-treated mice. We suggest that Rsv ineffectiveness could be caused by the low intracystic concentration (≈ 30 ± 2 μM) achieved in vivo and the drug´s hormetic effect, which accounts for the opposite anti-parasitic and immodulatory responses at different doses. Therefore, our assays do not allow us to propose to the RSV as a drug for the treatment of CE neither AE, due to it was perhaps not delivered and accumulated in the parasite in optimal amounts.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/276695
Paradoxical pharmacology effect of resveratrol against Echinococcosis; XXXIV Reunión Anual de Sociedad Argentina de Protozoología; La Plata; Argentina; 2023; 60-60
2953-5751
CONICET Digital
CONICET
url http://hdl.handle.net/11336/276695
identifier_str_mv Paradoxical pharmacology effect of resveratrol against Echinococcosis; XXXIV Reunión Anual de Sociedad Argentina de Protozoología; La Plata; Argentina; 2023; 60-60
2953-5751
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://protozoologia.org.ar/revista-parasitus/
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
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Protozoología
publisher.none.fl_str_mv Sociedad Argentina de Protozoología
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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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