Enzymatic pathways involved in flubendazole biotransformation

Autores
Maté, María Laura; Virkel, Guillermo Leon; Lifschitz, Adrian Luis; Ballent, Mariana; Sallovitz, Juan Manuel; Lanusse, Carlos Edmundo
Año de publicación
2007
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Flubendazole (FLBZ) is a benzimidazole anthelmintic widely used in poultry and swine, which may be an alternative drug for parasite control in ruminants. The objective of this work was to characterise the main enzymatic pathways involved in the hepatic biotransformation of FLBZ. Liver cytosols and microsomes were obtained from control and phenobarbital (PB)-induced female Wistar rats, and from untreated male Corriedale x Merino cross breed sheep. Subcellular fractions were incubated with 40 µM of either FLBZ or its reduced chiral metabolite (red-FLBZ) in presence of NADPH. Incubation mixtures were analysed by HPLC. Liver microsomes from control rat reduced FLBZ to red-FLBZ and oxidised the later back to the parent molecule. Microsomes obtained from PB-induced rats displayed higher cytochrome (CYP) 3A and 2C-mediated N-demethylase activities, which correlated with an enhanced ability to convert red-FLBZ into FLBZ. CYP-mediated oxidative metabolism of red-FLBZ to FLBZ was absent in sheep liver. Both cytosolic and microsomal fractions obtained from sheep liver were able to reduce FLBZ into red-FLBZ at the same rate; the reduction of FLBZ led to the prevalent (~98%) stereospecific formation of one of the enantiomeric forms of red-FLBZ. A NADPH-dependent ketone-reductase may be involved on FLBZ reduction in sheep liver. The study of drug metabolising enzyme activities may help to predict drug-drug metabolic interactions in Veterinary Therapeutics.
Fil: Maté, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; 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. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Ballent, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Sallovitz, Juan Manuel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
XXXIX Annual Scientific Meeting Argentine Society of Experimental Pharmacology
Ciudad Autónoma de Buenos Aires
Argentina
Sociedad Argentina de Farmacología Experimental
Materia
FLUIBENDAZOLE
ENZYMATIC PATHWAYS
RATS
SHEEP
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:11336/243735
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Enzymatic pathways involved in flubendazole biotransformationMaté, María LauraVirkel, Guillermo LeonLifschitz, Adrian LuisBallent, MarianaSallovitz, Juan ManuelLanusse, Carlos EdmundoFLUIBENDAZOLEENZYMATIC PATHWAYSRATSSHEEPhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Flubendazole (FLBZ) is a benzimidazole anthelmintic widely used in poultry and swine, which may be an alternative drug for parasite control in ruminants. The objective of this work was to characterise the main enzymatic pathways involved in the hepatic biotransformation of FLBZ. Liver cytosols and microsomes were obtained from control and phenobarbital (PB)-induced female Wistar rats, and from untreated male Corriedale x Merino cross breed sheep. Subcellular fractions were incubated with 40 µM of either FLBZ or its reduced chiral metabolite (red-FLBZ) in presence of NADPH. Incubation mixtures were analysed by HPLC. Liver microsomes from control rat reduced FLBZ to red-FLBZ and oxidised the later back to the parent molecule. Microsomes obtained from PB-induced rats displayed higher cytochrome (CYP) 3A and 2C-mediated N-demethylase activities, which correlated with an enhanced ability to convert red-FLBZ into FLBZ. CYP-mediated oxidative metabolism of red-FLBZ to FLBZ was absent in sheep liver. Both cytosolic and microsomal fractions obtained from sheep liver were able to reduce FLBZ into red-FLBZ at the same rate; the reduction of FLBZ led to the prevalent (~98%) stereospecific formation of one of the enantiomeric forms of red-FLBZ. A NADPH-dependent ketone-reductase may be involved on FLBZ reduction in sheep liver. The study of drug metabolising enzyme activities may help to predict drug-drug metabolic interactions in Veterinary Therapeutics.Fil: Maté, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; 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; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Ballent, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Sallovitz, Juan Manuel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaXXXIX Annual Scientific Meeting Argentine Society of Experimental PharmacologyCiudad Autónoma de Buenos AiresArgentinaSociedad Argentina de Farmacología ExperimentalSociedad Argentina de Farmacología Experimental2007info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/mswordapplication/pdfhttp://hdl.handle.net/11336/243735Enzymatic pathways involved in flubendazole biotransformation; XXXIX Annual Scientific Meeting Argentine Society of Experimental Pharmacology; Ciudad Autónoma de Buenos Aires; Argentina; 2007; 89-89CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/wp-content/uploads/2021/07/ACTA_2007.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:11:33Zoai:ri.conicet.gov.ar:11336/243735instacron: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:34982025-10-22 12:11:33.521CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Enzymatic pathways involved in flubendazole biotransformation
title Enzymatic pathways involved in flubendazole biotransformation
spellingShingle Enzymatic pathways involved in flubendazole biotransformation
Maté, María Laura
FLUIBENDAZOLE
ENZYMATIC PATHWAYS
RATS
SHEEP
title_short Enzymatic pathways involved in flubendazole biotransformation
title_full Enzymatic pathways involved in flubendazole biotransformation
title_fullStr Enzymatic pathways involved in flubendazole biotransformation
title_full_unstemmed Enzymatic pathways involved in flubendazole biotransformation
title_sort Enzymatic pathways involved in flubendazole biotransformation
dc.creator.none.fl_str_mv Maté, María Laura
Virkel, Guillermo Leon
Lifschitz, Adrian Luis
Ballent, Mariana
Sallovitz, Juan Manuel
Lanusse, Carlos Edmundo
author Maté, María Laura
author_facet Maté, María Laura
Virkel, Guillermo Leon
Lifschitz, Adrian Luis
Ballent, Mariana
Sallovitz, Juan Manuel
Lanusse, Carlos Edmundo
author_role author
author2 Virkel, Guillermo Leon
Lifschitz, Adrian Luis
Ballent, Mariana
Sallovitz, Juan Manuel
Lanusse, Carlos Edmundo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv FLUIBENDAZOLE
ENZYMATIC PATHWAYS
RATS
SHEEP
topic FLUIBENDAZOLE
ENZYMATIC PATHWAYS
RATS
SHEEP
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Flubendazole (FLBZ) is a benzimidazole anthelmintic widely used in poultry and swine, which may be an alternative drug for parasite control in ruminants. The objective of this work was to characterise the main enzymatic pathways involved in the hepatic biotransformation of FLBZ. Liver cytosols and microsomes were obtained from control and phenobarbital (PB)-induced female Wistar rats, and from untreated male Corriedale x Merino cross breed sheep. Subcellular fractions were incubated with 40 µM of either FLBZ or its reduced chiral metabolite (red-FLBZ) in presence of NADPH. Incubation mixtures were analysed by HPLC. Liver microsomes from control rat reduced FLBZ to red-FLBZ and oxidised the later back to the parent molecule. Microsomes obtained from PB-induced rats displayed higher cytochrome (CYP) 3A and 2C-mediated N-demethylase activities, which correlated with an enhanced ability to convert red-FLBZ into FLBZ. CYP-mediated oxidative metabolism of red-FLBZ to FLBZ was absent in sheep liver. Both cytosolic and microsomal fractions obtained from sheep liver were able to reduce FLBZ into red-FLBZ at the same rate; the reduction of FLBZ led to the prevalent (~98%) stereospecific formation of one of the enantiomeric forms of red-FLBZ. A NADPH-dependent ketone-reductase may be involved on FLBZ reduction in sheep liver. The study of drug metabolising enzyme activities may help to predict drug-drug metabolic interactions in Veterinary Therapeutics.
Fil: Maté, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; 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. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Ballent, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Sallovitz, Juan Manuel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
XXXIX Annual Scientific Meeting Argentine Society of Experimental Pharmacology
Ciudad Autónoma de Buenos Aires
Argentina
Sociedad Argentina de Farmacología Experimental
description Flubendazole (FLBZ) is a benzimidazole anthelmintic widely used in poultry and swine, which may be an alternative drug for parasite control in ruminants. The objective of this work was to characterise the main enzymatic pathways involved in the hepatic biotransformation of FLBZ. Liver cytosols and microsomes were obtained from control and phenobarbital (PB)-induced female Wistar rats, and from untreated male Corriedale x Merino cross breed sheep. Subcellular fractions were incubated with 40 µM of either FLBZ or its reduced chiral metabolite (red-FLBZ) in presence of NADPH. Incubation mixtures were analysed by HPLC. Liver microsomes from control rat reduced FLBZ to red-FLBZ and oxidised the later back to the parent molecule. Microsomes obtained from PB-induced rats displayed higher cytochrome (CYP) 3A and 2C-mediated N-demethylase activities, which correlated with an enhanced ability to convert red-FLBZ into FLBZ. CYP-mediated oxidative metabolism of red-FLBZ to FLBZ was absent in sheep liver. Both cytosolic and microsomal fractions obtained from sheep liver were able to reduce FLBZ into red-FLBZ at the same rate; the reduction of FLBZ led to the prevalent (~98%) stereospecific formation of one of the enantiomeric forms of red-FLBZ. A NADPH-dependent ketone-reductase may be involved on FLBZ reduction in sheep liver. The study of drug metabolising enzyme activities may help to predict drug-drug metabolic interactions in Veterinary Therapeutics.
publishDate 2007
dc.date.none.fl_str_mv 2007
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Book
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/11336/243735
Enzymatic pathways involved in flubendazole biotransformation; XXXIX Annual Scientific Meeting Argentine Society of Experimental Pharmacology; Ciudad Autónoma de Buenos Aires; Argentina; 2007; 89-89
CONICET Digital
CONICET
url http://hdl.handle.net/11336/243735
identifier_str_mv Enzymatic pathways involved in flubendazole biotransformation; XXXIX Annual Scientific Meeting Argentine Society of Experimental Pharmacology; Ciudad Autónoma de Buenos Aires; Argentina; 2007; 89-89
CONICET Digital
CONICET
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language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/wp-content/uploads/2021/07/ACTA_2007.pdf
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Farmacología Experimental
publisher.none.fl_str_mv Sociedad Argentina de Farmacología Experimental
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reponame_str CONICET Digital (CONICET)
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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