Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde

Autores
Miró, María Victoria; Ichinose, Paula; Lloberas, Maria Mercedes; Lanusse, Carlos Edmundo; Virkel, Guillermo Leon; Lifschitz, Adrian Luis
Año de publicación
2025
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Considering the increase of nematode resis-tance to the synthetic anthelmintic drugs, newcontrol strategies are urgently needed. While many phytochemical compounds show in vitroantiparasitic activity, their in vivo therapeutic potential remains underexplored. Both theex vivo and in vivo effects of cinnamaldehyde (CNM) and thymol (TML) on the doramectin(DRM) and levamisole (LVM) nematodicidal response were assessed in naturally infected lambs. The interaction on intestinal absorption/secretion by CNM, TML (1.5 mM) DRM and LVM(5 μM) was assessed using a diffusion chamber model with Rho123 (0.5 μM) as a substrate across lamb ileum tissue. Two in vivo trials(T1 and T2) examined the interactions between monoterpenes and the synthetic anthelmintics. In T1, CNM (100 mg/kg, orally at 0 and 24h) was combined with DRM (0.2 mg/kg, SC),with outcomes evaluated over two years. In T2,lambs received LVM (3.75 mg/kg, SC) alone orcombined with CNM or TML (80 mg/kg, SC at0 and 3 h). Drug plasma levels were measuredby HPLC and fecal egg count reduction (FECR) were used to assess efficacy. CNM and LVM decreased Rho123 efflux across lamb intestine,suggesting a drug transport-related interaction.In T1, co-administration with CNM increased DRM efficacy from 66.3% to 78.0% (first treat-ment year); however, no significant differences in efficacy or pharmacokinetic (PK) parameters were observed in the second year between the DRM and DRM+CNM groups. In T2, both CNMand TML enhanced LVM systemic exposure,increasing the area under the curve (AUC) by20–50%. Despite this PK interaction, treatment efficacy remained comparable for LVM+C-NM (55.5%), LVM+TML (57.8%) and LVM alone(51.4%). These results suggest that the phytochemicals CNM and TML may induce drug PK and/or pharmacodynamics interactions both ex-vivo and in-vivo. Overall, the findings offervaluable insights into the potential of phytochemicals as antiparasitic agents and on their interactions with conventional anthelmintics.
Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Ichinose, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lloberas, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
30th Conference of the World Association for the Advancement of Veterinary Parasitology
Curitiba
Brasil
World Association for the Advancement of Veterinary Parasitology
Materia
ANTIPARASITIC
THYMOL
CINNAMALDEHYDE
DORAMECTIN
INFECTED LAMBS
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:11336/279421

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network_name_str CONICET Digital (CONICET)
spelling Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehydeMiró, María VictoriaIchinose, PaulaLloberas, Maria MercedesLanusse, Carlos EdmundoVirkel, Guillermo LeonLifschitz, Adrian LuisANTIPARASITICTHYMOLCINNAMALDEHYDEDORAMECTININFECTED LAMBShttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Considering the increase of nematode resis-tance to the synthetic anthelmintic drugs, newcontrol strategies are urgently needed. While many phytochemical compounds show in vitroantiparasitic activity, their in vivo therapeutic potential remains underexplored. Both theex vivo and in vivo effects of cinnamaldehyde (CNM) and thymol (TML) on the doramectin(DRM) and levamisole (LVM) nematodicidal response were assessed in naturally infected lambs. The interaction on intestinal absorption/secretion by CNM, TML (1.5 mM) DRM and LVM(5 μM) was assessed using a diffusion chamber model with Rho123 (0.5 μM) as a substrate across lamb ileum tissue. Two in vivo trials(T1 and T2) examined the interactions between monoterpenes and the synthetic anthelmintics. In T1, CNM (100 mg/kg, orally at 0 and 24h) was combined with DRM (0.2 mg/kg, SC),with outcomes evaluated over two years. In T2,lambs received LVM (3.75 mg/kg, SC) alone orcombined with CNM or TML (80 mg/kg, SC at0 and 3 h). Drug plasma levels were measuredby HPLC and fecal egg count reduction (FECR) were used to assess efficacy. CNM and LVM decreased Rho123 efflux across lamb intestine,suggesting a drug transport-related interaction.In T1, co-administration with CNM increased DRM efficacy from 66.3% to 78.0% (first treat-ment year); however, no significant differences in efficacy or pharmacokinetic (PK) parameters were observed in the second year between the DRM and DRM+CNM groups. In T2, both CNMand TML enhanced LVM systemic exposure,increasing the area under the curve (AUC) by20–50%. Despite this PK interaction, treatment efficacy remained comparable for LVM+C-NM (55.5%), LVM+TML (57.8%) and LVM alone(51.4%). These results suggest that the phytochemicals CNM and TML may induce drug PK and/or pharmacodynamics interactions both ex-vivo and in-vivo. Overall, the findings offervaluable insights into the potential of phytochemicals as antiparasitic agents and on their interactions with conventional anthelmintics.Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Ichinose, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lloberas, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina30th Conference of the World Association for the Advancement of Veterinary ParasitologyCuritibaBrasilWorld Association for the Advancement of Veterinary ParasitologyWorld Association for the Advancement of Veterinary Parasitology2025info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectConferenciaBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/279421Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde; 30th Conference of the World Association for the Advancement of Veterinary Parasitology; Curitiba; Brasil; 2025; 197-198CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://waavp2025.com/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 Técnicas2026-02-26T10:09:45Zoai:ri.conicet.gov.ar:11336/279421instacron: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:34982026-02-26 10:09:46.205CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde
title Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde
spellingShingle Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde
Miró, María Victoria
ANTIPARASITIC
THYMOL
CINNAMALDEHYDE
DORAMECTIN
INFECTED LAMBS
title_short Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde
title_full Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde
title_fullStr Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde
title_full_unstemmed Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde
title_sort Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde
dc.creator.none.fl_str_mv Miró, María Victoria
Ichinose, Paula
Lloberas, Maria Mercedes
Lanusse, Carlos Edmundo
Virkel, Guillermo Leon
Lifschitz, Adrian Luis
author Miró, María Victoria
author_facet Miró, María Victoria
Ichinose, Paula
Lloberas, Maria Mercedes
Lanusse, Carlos Edmundo
Virkel, Guillermo Leon
Lifschitz, Adrian Luis
author_role author
author2 Ichinose, Paula
Lloberas, Maria Mercedes
Lanusse, Carlos Edmundo
Virkel, Guillermo Leon
Lifschitz, Adrian Luis
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ANTIPARASITIC
THYMOL
CINNAMALDEHYDE
DORAMECTIN
INFECTED LAMBS
topic ANTIPARASITIC
THYMOL
CINNAMALDEHYDE
DORAMECTIN
INFECTED LAMBS
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Considering the increase of nematode resis-tance to the synthetic anthelmintic drugs, newcontrol strategies are urgently needed. While many phytochemical compounds show in vitroantiparasitic activity, their in vivo therapeutic potential remains underexplored. Both theex vivo and in vivo effects of cinnamaldehyde (CNM) and thymol (TML) on the doramectin(DRM) and levamisole (LVM) nematodicidal response were assessed in naturally infected lambs. The interaction on intestinal absorption/secretion by CNM, TML (1.5 mM) DRM and LVM(5 μM) was assessed using a diffusion chamber model with Rho123 (0.5 μM) as a substrate across lamb ileum tissue. Two in vivo trials(T1 and T2) examined the interactions between monoterpenes and the synthetic anthelmintics. In T1, CNM (100 mg/kg, orally at 0 and 24h) was combined with DRM (0.2 mg/kg, SC),with outcomes evaluated over two years. In T2,lambs received LVM (3.75 mg/kg, SC) alone orcombined with CNM or TML (80 mg/kg, SC at0 and 3 h). Drug plasma levels were measuredby HPLC and fecal egg count reduction (FECR) were used to assess efficacy. CNM and LVM decreased Rho123 efflux across lamb intestine,suggesting a drug transport-related interaction.In T1, co-administration with CNM increased DRM efficacy from 66.3% to 78.0% (first treat-ment year); however, no significant differences in efficacy or pharmacokinetic (PK) parameters were observed in the second year between the DRM and DRM+CNM groups. In T2, both CNMand TML enhanced LVM systemic exposure,increasing the area under the curve (AUC) by20–50%. Despite this PK interaction, treatment efficacy remained comparable for LVM+C-NM (55.5%), LVM+TML (57.8%) and LVM alone(51.4%). These results suggest that the phytochemicals CNM and TML may induce drug PK and/or pharmacodynamics interactions both ex-vivo and in-vivo. Overall, the findings offervaluable insights into the potential of phytochemicals as antiparasitic agents and on their interactions with conventional anthelmintics.
Fil: Miró, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Ichinose, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lloberas, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Virkel, Guillermo Leon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
30th Conference of the World Association for the Advancement of Veterinary Parasitology
Curitiba
Brasil
World Association for the Advancement of Veterinary Parasitology
description Considering the increase of nematode resis-tance to the synthetic anthelmintic drugs, newcontrol strategies are urgently needed. While many phytochemical compounds show in vitroantiparasitic activity, their in vivo therapeutic potential remains underexplored. Both theex vivo and in vivo effects of cinnamaldehyde (CNM) and thymol (TML) on the doramectin(DRM) and levamisole (LVM) nematodicidal response were assessed in naturally infected lambs. The interaction on intestinal absorption/secretion by CNM, TML (1.5 mM) DRM and LVM(5 μM) was assessed using a diffusion chamber model with Rho123 (0.5 μM) as a substrate across lamb ileum tissue. Two in vivo trials(T1 and T2) examined the interactions between monoterpenes and the synthetic anthelmintics. In T1, CNM (100 mg/kg, orally at 0 and 24h) was combined with DRM (0.2 mg/kg, SC),with outcomes evaluated over two years. In T2,lambs received LVM (3.75 mg/kg, SC) alone orcombined with CNM or TML (80 mg/kg, SC at0 and 3 h). Drug plasma levels were measuredby HPLC and fecal egg count reduction (FECR) were used to assess efficacy. CNM and LVM decreased Rho123 efflux across lamb intestine,suggesting a drug transport-related interaction.In T1, co-administration with CNM increased DRM efficacy from 66.3% to 78.0% (first treat-ment year); however, no significant differences in efficacy or pharmacokinetic (PK) parameters were observed in the second year between the DRM and DRM+CNM groups. In T2, both CNMand TML enhanced LVM systemic exposure,increasing the area under the curve (AUC) by20–50%. Despite this PK interaction, treatment efficacy remained comparable for LVM+C-NM (55.5%), LVM+TML (57.8%) and LVM alone(51.4%). These results suggest that the phytochemicals CNM and TML may induce drug PK and/or pharmacodynamics interactions both ex-vivo and in-vivo. Overall, the findings offervaluable insights into the potential of phytochemicals as antiparasitic agents and on their interactions with conventional anthelmintics.
publishDate 2025
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/279421
Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde; 30th Conference of the World Association for the Advancement of Veterinary Parasitology; Curitiba; Brasil; 2025; 197-198
CONICET Digital
CONICET
url http://hdl.handle.net/11336/279421
identifier_str_mv Ex vivo and in vivo pharmacological inte- raction between antiparasitic drugs and the phytochemical monoterpenes thymol and cinnamaldehyde; 30th Conference of the World Association for the Advancement of Veterinary Parasitology; Curitiba; Brasil; 2025; 197-198
CONICET Digital
CONICET
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