Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver

Autores
Ichinose, Paula; Miró, María Victoria; Larsen, Karen Elizabeth; Lanusse, Carlos Edmundo; Lifschitz, Adrian Luis; Virkel, Guillermo Leon
Año de publicación
2022
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Fenbendazole (FBZ), a benzymidazole (BZD) drug, is used to control gastrointestinal parasites in continuous administration in swine. This drug undergoes two sequential S-oxidations through mixed function oxidases belonging to the cytochrome P450 (CYP) and flavin-monooxygenase (FMO) families. Also, BZD-containing drugs may induce the CYP1A subfamily. This work aimed to evaluate in vitro the effect of FBZ on CYP1A-dependent enzyme activities in pig liver. Five (5) piglets remained untreated (controls) and other six (6) were treated with a FBZ commercial powder mixed with food, in two dosing events repeated for 10 consecutive days, as usually is recommended. Both groups were fed ad libitum for 10 days and then euthanized for preparation of liver microsomes. FBZ and its 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). Concentrations (µg/g) of FBZ, OFZ and FBZSO2 in liver parenchyma were 4.66±1.59, 3.11±1.06 and 2.30±0.99, respectively. In liver microsomes from treated animals, CYP1A-dependent enzyme activities, 7-ethoxuresorufin O-deethylase and methoxyresorufin O-demethylase, increased 24.5-fold (p=0.003) and 17.2-fold (p=0.001), respectively. The participation of the CYP pathway in the S-oxidation of FBZ into OFZ was also enhanced (3.4-fold, p=0.004) in piglets which received the anthelmintic with food (61.8±19.5 pmol/min.mg) compared to controls (18.0±6.0 pmol/min.mg). Thus, FBZ may auto-induce its own metabolism though the CYP1A pathway. This fact may also affect the fate of other xenobiotics that share the same metabolic pattern, like 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: 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: 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
American Academy of Veterinary Pharmacology and Therapeutics Special Online Student Research Symposium
Estados Unidos
American Academy of Veterinary Pharmacology and Therapeutics
Materia
FENBENDAZOLE
METABOLISM
CYTOCHROME p450
INDUCTION
PIG LIVER
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:11336/225117
Acceder
id CONICETDig_ea4926eec44759a1c76d9cfe29054aff
oai_identifier_str oai:ri.conicet.gov.ar:11336/225117
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liverIchinose, PaulaMiró, María VictoriaLarsen, Karen ElizabethLanusse, Carlos EdmundoLifschitz, Adrian LuisVirkel, Guillermo LeonFENBENDAZOLEMETABOLISMCYTOCHROME p450INDUCTIONPIG LIVERhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Fenbendazole (FBZ), a benzymidazole (BZD) drug, is used to control gastrointestinal parasites in continuous administration in swine. This drug undergoes two sequential S-oxidations through mixed function oxidases belonging to the cytochrome P450 (CYP) and flavin-monooxygenase (FMO) families. Also, BZD-containing drugs may induce the CYP1A subfamily. This work aimed to evaluate in vitro the effect of FBZ on CYP1A-dependent enzyme activities in pig liver. Five (5) piglets remained untreated (controls) and other six (6) were treated with a FBZ commercial powder mixed with food, in two dosing events repeated for 10 consecutive days, as usually is recommended. Both groups were fed ad libitum for 10 days and then euthanized for preparation of liver microsomes. FBZ and its 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). Concentrations (µg/g) of FBZ, OFZ and FBZSO2 in liver parenchyma were 4.66±1.59, 3.11±1.06 and 2.30±0.99, respectively. In liver microsomes from treated animals, CYP1A-dependent enzyme activities, 7-ethoxuresorufin O-deethylase and methoxyresorufin O-demethylase, increased 24.5-fold (p=0.003) and 17.2-fold (p=0.001), respectively. The participation of the CYP pathway in the S-oxidation of FBZ into OFZ was also enhanced (3.4-fold, p=0.004) in piglets which received the anthelmintic with food (61.8±19.5 pmol/min.mg) compared to controls (18.0±6.0 pmol/min.mg). Thus, FBZ may auto-induce its own metabolism though the CYP1A pathway. This fact may also affect the fate of other xenobiotics that share the same metabolic pattern, like 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: 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: 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; ArgentinaAmerican Academy of Veterinary Pharmacology and Therapeutics Special Online Student Research SymposiumEstados UnidosAmerican Academy of Veterinary Pharmacology and TherapeuticsAmerican Academy of Veterinary Pharmacology and Therapeutics2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/225117Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver; American Academy of Veterinary Pharmacology and Therapeutics Special Online Student Research Symposium; Estados Unidos; 2022; 8-8CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://cdn.ymaws.com/www.aavpt.org/resource/resmgr/proceedings/aavpt_online_student_researc.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 Técnicas2025-09-03T09:49:19Zoai:ri.conicet.gov.ar:11336/225117instacron: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 09:49:20.149CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver
title Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver
spellingShingle Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver
Ichinose, Paula
FENBENDAZOLE
METABOLISM
CYTOCHROME p450
INDUCTION
PIG LIVER
title_short Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver
title_full Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver
title_fullStr Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver
title_full_unstemmed Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver
title_sort Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver
dc.creator.none.fl_str_mv Ichinose, Paula
Miró, María Victoria
Larsen, Karen Elizabeth
Lanusse, Carlos Edmundo
Lifschitz, Adrian Luis
Virkel, Guillermo Leon
author Ichinose, Paula
author_facet Ichinose, Paula
Miró, María Victoria
Larsen, Karen Elizabeth
Lanusse, Carlos Edmundo
Lifschitz, Adrian Luis
Virkel, Guillermo Leon
author_role author
author2 Miró, María Victoria
Larsen, Karen Elizabeth
Lanusse, Carlos Edmundo
Lifschitz, Adrian Luis
Virkel, Guillermo Leon
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv FENBENDAZOLE
METABOLISM
CYTOCHROME p450
INDUCTION
PIG LIVER
topic FENBENDAZOLE
METABOLISM
CYTOCHROME p450
INDUCTION
PIG LIVER
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Fenbendazole (FBZ), a benzymidazole (BZD) drug, is used to control gastrointestinal parasites in continuous administration in swine. This drug undergoes two sequential S-oxidations through mixed function oxidases belonging to the cytochrome P450 (CYP) and flavin-monooxygenase (FMO) families. Also, BZD-containing drugs may induce the CYP1A subfamily. This work aimed to evaluate in vitro the effect of FBZ on CYP1A-dependent enzyme activities in pig liver. Five (5) piglets remained untreated (controls) and other six (6) were treated with a FBZ commercial powder mixed with food, in two dosing events repeated for 10 consecutive days, as usually is recommended. Both groups were fed ad libitum for 10 days and then euthanized for preparation of liver microsomes. FBZ and its 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). Concentrations (µg/g) of FBZ, OFZ and FBZSO2 in liver parenchyma were 4.66±1.59, 3.11±1.06 and 2.30±0.99, respectively. In liver microsomes from treated animals, CYP1A-dependent enzyme activities, 7-ethoxuresorufin O-deethylase and methoxyresorufin O-demethylase, increased 24.5-fold (p=0.003) and 17.2-fold (p=0.001), respectively. The participation of the CYP pathway in the S-oxidation of FBZ into OFZ was also enhanced (3.4-fold, p=0.004) in piglets which received the anthelmintic with food (61.8±19.5 pmol/min.mg) compared to controls (18.0±6.0 pmol/min.mg). Thus, FBZ may auto-induce its own metabolism though the CYP1A pathway. This fact may also affect the fate of other xenobiotics that share the same metabolic pattern, like 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: 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: 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
American Academy of Veterinary Pharmacology and Therapeutics Special Online Student Research Symposium
Estados Unidos
American Academy of Veterinary Pharmacology and Therapeutics
description Fenbendazole (FBZ), a benzymidazole (BZD) drug, is used to control gastrointestinal parasites in continuous administration in swine. This drug undergoes two sequential S-oxidations through mixed function oxidases belonging to the cytochrome P450 (CYP) and flavin-monooxygenase (FMO) families. Also, BZD-containing drugs may induce the CYP1A subfamily. This work aimed to evaluate in vitro the effect of FBZ on CYP1A-dependent enzyme activities in pig liver. Five (5) piglets remained untreated (controls) and other six (6) were treated with a FBZ commercial powder mixed with food, in two dosing events repeated for 10 consecutive days, as usually is recommended. Both groups were fed ad libitum for 10 days and then euthanized for preparation of liver microsomes. FBZ and its 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). Concentrations (µg/g) of FBZ, OFZ and FBZSO2 in liver parenchyma were 4.66±1.59, 3.11±1.06 and 2.30±0.99, respectively. In liver microsomes from treated animals, CYP1A-dependent enzyme activities, 7-ethoxuresorufin O-deethylase and methoxyresorufin O-demethylase, increased 24.5-fold (p=0.003) and 17.2-fold (p=0.001), respectively. The participation of the CYP pathway in the S-oxidation of FBZ into OFZ was also enhanced (3.4-fold, p=0.004) in piglets which received the anthelmintic with food (61.8±19.5 pmol/min.mg) compared to controls (18.0±6.0 pmol/min.mg). Thus, FBZ may auto-induce its own metabolism though the CYP1A pathway. This fact may also affect the fate of other xenobiotics that share the same metabolic pattern, like aflatoxin B1 present in certain pig foodstuffs.
publishDate 2022
dc.date.none.fl_str_mv 2022
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info:eu-repo/semantics/conferenceObject
Congreso
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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/11336/225117
Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver; American Academy of Veterinary Pharmacology and Therapeutics Special Online Student Research Symposium; Estados Unidos; 2022; 8-8
CONICET Digital
CONICET
url http://hdl.handle.net/11336/225117
identifier_str_mv Fenbendazole administration induces cytochrome P450 1a-dependent enzyme activities in pig liver; American Academy of Veterinary Pharmacology and Therapeutics Special Online Student Research Symposium; Estados Unidos; 2022; 8-8
CONICET Digital
CONICET
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language eng
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv American Academy of Veterinary Pharmacology and Therapeutics
publisher.none.fl_str_mv American Academy of Veterinary Pharmacology and Therapeutics
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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