Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine

Autores
Ichinose, Paula; Miró, María Victoria; Larsen, Karen Elizabeth; Lifschitz, Adrian Luis; Virkel, Guillermo Leon
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The anthelmintic fenbendazole (FBZ), a benzymidazole (BZD) drug, is used to control gastrointestinal parasites in swine production. This compound is commercially available as a powder to be mixed with food for oral administration in pigs for 7-10 days. BZD-containing drugs possess the ability to significantly induce certain cytochrome P450 (CYP) isozymes in different species, particularly those belonging to the CYP1A family. This work aimed to evaluate in vitro the effect FBZ sustained administration on CYP1A-dependent enzyme activities in pig liver. Eleven (11) piglets were divided in two groups: five (5) animals remained untreated and used as controls; six (6) animals were treated with a FBZ commercial powder mixed with food. The drug concentration in food was 0.01% and animals were fed ad libitum for 10 days. Animals were euthanized for preparation of liver microsomes. Two CYP 1A-dependent enzyme activities, namely 7-ethoxuresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) were assayed in a spectrofluorometer. FBZ and its S-oxygenated metabolites, oxfendazole (OFZ) and fenbendazole sulphone (FBZSO2), were detected in the systemic circulation of treated piglets. Mean plasma AUCs (µg.day/mL) were 0.28±0.08 (FBZ), 4.10±0.58 (OFZ) and 4.56±1.01 (FBZSO2). The parent drug FBZ represented around the 46% (4.66±1.59 µg/g) of the total anthelmintic molecules in the liver, followed by OFZ (3.11±1.06 µg/g, 31%) and the inactive FBZSO2 (2.30±0.99 µg/mL, 23%). In liver microsomes from treated animals, both EROD and MROD enzyme activities increased 24.5-fold (p=0.003) and 17.2-fold (p=0.0006), respectively. The sustained administration of FBZ caused the induction of the CYP1A-dependent metabolism in pig liver. This fact may affect the metabolic fate of FBZ itself but also of other foreign compounds such as aflatoxin B1 present in certain pig foodstuffs.
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: 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: Larsen, Karen Elizabeth. 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
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
LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de La Asociación Argentina de Farmacología Experimental y XI Reunión Anual de La Asociación Argentina de Nanomedicinas
Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
Materia
FENBENDAZOLE
CYTOCHROME P450
SWINE
ENZYME ACTIVITIES
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:11336/169777
Acceder
id CONICETDig_ba2c4828d8e05343a7d34dd62058b241
oai_identifier_str oai:ri.conicet.gov.ar:11336/169777
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swineIchinose, PaulaMiró, María VictoriaLarsen, Karen ElizabethLifschitz, Adrian LuisVirkel, Guillermo LeonFENBENDAZOLECYTOCHROME P450SWINEENZYME ACTIVITIEShttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4The anthelmintic fenbendazole (FBZ), a benzymidazole (BZD) drug, is used to control gastrointestinal parasites in swine production. This compound is commercially available as a powder to be mixed with food for oral administration in pigs for 7-10 days. BZD-containing drugs possess the ability to significantly induce certain cytochrome P450 (CYP) isozymes in different species, particularly those belonging to the CYP1A family. This work aimed to evaluate in vitro the effect FBZ sustained administration on CYP1A-dependent enzyme activities in pig liver. Eleven (11) piglets were divided in two groups: five (5) animals remained untreated and used as controls; six (6) animals were treated with a FBZ commercial powder mixed with food. The drug concentration in food was 0.01% and animals were fed ad libitum for 10 days. Animals were euthanized for preparation of liver microsomes. Two CYP 1A-dependent enzyme activities, namely 7-ethoxuresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) were assayed in a spectrofluorometer. FBZ and its S-oxygenated metabolites, oxfendazole (OFZ) and fenbendazole sulphone (FBZSO2), were detected in the systemic circulation of treated piglets. Mean plasma AUCs (µg.day/mL) were 0.28±0.08 (FBZ), 4.10±0.58 (OFZ) and 4.56±1.01 (FBZSO2). The parent drug FBZ represented around the 46% (4.66±1.59 µg/g) of the total anthelmintic molecules in the liver, followed by OFZ (3.11±1.06 µg/g, 31%) and the inactive FBZSO2 (2.30±0.99 µg/mL, 23%). In liver microsomes from treated animals, both EROD and MROD enzyme activities increased 24.5-fold (p=0.003) and 17.2-fold (p=0.0006), respectively. The sustained administration of FBZ caused the induction of the CYP1A-dependent metabolism in pig liver. This fact may affect the metabolic fate of FBZ itself but also of other foreign compounds such as aflatoxin B1 present in certain pig foodstuffs.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; ArgentinaFil: 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: Larsen, Karen Elizabeth. 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; 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; ArgentinaLXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de La Asociación Argentina de Farmacología Experimental y XI Reunión Anual de La Asociación Argentina de NanomedicinasBuenos AiresArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de NanomedicinasFundación Revista Medicina2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/169777Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de La Asociación Argentina de Farmacología Experimental y XI Reunión Anual de La Asociación Argentina de Nanomedicinas; Buenos Aires; Argentina; 2021; 94-941669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol81-21/s3/Mv81s3.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:00Zoai:ri.conicet.gov.ar:11336/169777instacron: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:34982025-09-03 10:11:01.187CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine
title Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine
spellingShingle Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine
Ichinose, Paula
FENBENDAZOLE
CYTOCHROME P450
SWINE
ENZYME ACTIVITIES
title_short Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine
title_full Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine
title_fullStr Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine
title_full_unstemmed Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine
title_sort Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine
dc.creator.none.fl_str_mv Ichinose, Paula
Miró, María Victoria
Larsen, Karen Elizabeth
Lifschitz, Adrian Luis
Virkel, Guillermo Leon
author Ichinose, Paula
author_facet Ichinose, Paula
Miró, María Victoria
Larsen, Karen Elizabeth
Lifschitz, Adrian Luis
Virkel, Guillermo Leon
author_role author
author2 Miró, María Victoria
Larsen, Karen Elizabeth
Lifschitz, Adrian Luis
Virkel, Guillermo Leon
author2_role author
author
author
author
dc.subject.none.fl_str_mv FENBENDAZOLE
CYTOCHROME P450
SWINE
ENZYME ACTIVITIES
topic FENBENDAZOLE
CYTOCHROME P450
SWINE
ENZYME ACTIVITIES
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv The anthelmintic fenbendazole (FBZ), a benzymidazole (BZD) drug, is used to control gastrointestinal parasites in swine production. This compound is commercially available as a powder to be mixed with food for oral administration in pigs for 7-10 days. BZD-containing drugs possess the ability to significantly induce certain cytochrome P450 (CYP) isozymes in different species, particularly those belonging to the CYP1A family. This work aimed to evaluate in vitro the effect FBZ sustained administration on CYP1A-dependent enzyme activities in pig liver. Eleven (11) piglets were divided in two groups: five (5) animals remained untreated and used as controls; six (6) animals were treated with a FBZ commercial powder mixed with food. The drug concentration in food was 0.01% and animals were fed ad libitum for 10 days. Animals were euthanized for preparation of liver microsomes. Two CYP 1A-dependent enzyme activities, namely 7-ethoxuresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) were assayed in a spectrofluorometer. FBZ and its S-oxygenated metabolites, oxfendazole (OFZ) and fenbendazole sulphone (FBZSO2), were detected in the systemic circulation of treated piglets. Mean plasma AUCs (µg.day/mL) were 0.28±0.08 (FBZ), 4.10±0.58 (OFZ) and 4.56±1.01 (FBZSO2). The parent drug FBZ represented around the 46% (4.66±1.59 µg/g) of the total anthelmintic molecules in the liver, followed by OFZ (3.11±1.06 µg/g, 31%) and the inactive FBZSO2 (2.30±0.99 µg/mL, 23%). In liver microsomes from treated animals, both EROD and MROD enzyme activities increased 24.5-fold (p=0.003) and 17.2-fold (p=0.0006), respectively. The sustained administration of FBZ caused the induction of the CYP1A-dependent metabolism in pig liver. This fact may affect the metabolic fate of FBZ itself but also of other foreign compounds such as aflatoxin B1 present in certain pig foodstuffs.
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: 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: Larsen, Karen Elizabeth. 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
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
LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de La Asociación Argentina de Farmacología Experimental y XI Reunión Anual de La Asociación Argentina de Nanomedicinas
Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Asociación Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
description The anthelmintic fenbendazole (FBZ), a benzymidazole (BZD) drug, is used to control gastrointestinal parasites in swine production. This compound is commercially available as a powder to be mixed with food for oral administration in pigs for 7-10 days. BZD-containing drugs possess the ability to significantly induce certain cytochrome P450 (CYP) isozymes in different species, particularly those belonging to the CYP1A family. This work aimed to evaluate in vitro the effect FBZ sustained administration on CYP1A-dependent enzyme activities in pig liver. Eleven (11) piglets were divided in two groups: five (5) animals remained untreated and used as controls; six (6) animals were treated with a FBZ commercial powder mixed with food. The drug concentration in food was 0.01% and animals were fed ad libitum for 10 days. Animals were euthanized for preparation of liver microsomes. Two CYP 1A-dependent enzyme activities, namely 7-ethoxuresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) were assayed in a spectrofluorometer. FBZ and its S-oxygenated metabolites, oxfendazole (OFZ) and fenbendazole sulphone (FBZSO2), were detected in the systemic circulation of treated piglets. Mean plasma AUCs (µg.day/mL) were 0.28±0.08 (FBZ), 4.10±0.58 (OFZ) and 4.56±1.01 (FBZSO2). The parent drug FBZ represented around the 46% (4.66±1.59 µg/g) of the total anthelmintic molecules in the liver, followed by OFZ (3.11±1.06 µg/g, 31%) and the inactive FBZSO2 (2.30±0.99 µg/mL, 23%). In liver microsomes from treated animals, both EROD and MROD enzyme activities increased 24.5-fold (p=0.003) and 17.2-fold (p=0.0006), respectively. The sustained administration of FBZ caused the induction of the CYP1A-dependent metabolism in pig liver. This fact may affect the metabolic fate of FBZ itself but also of other foreign compounds such as aflatoxin B1 present in certain pig foodstuffs.
publishDate 2021
dc.date.none.fl_str_mv 2021
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/11336/169777
Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de La Asociación Argentina de Farmacología Experimental y XI Reunión Anual de La Asociación Argentina de Nanomedicinas; Buenos Aires; Argentina; 2021; 94-94
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/169777
identifier_str_mv Sustained treatment with fenbendazole induces cytochrome P450 enzyme activities in swine; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXIX Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de La Asociación Argentina de Farmacología Experimental y XI Reunión Anual de La Asociación Argentina de Nanomedicinas; Buenos Aires; Argentina; 2021; 94-94
1669-9106
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://medicinabuenosaires.com/revistas/vol81-21/s3/Mv81s3.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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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