Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole

Autores
Devine, Catherine; Brennan, Gerard P.; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Trudgett, Alan G.; Hoey, Elizabeth M.; Fairweather, Ian
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP P450) system was inhibited using piperonyl butoxide (PB). The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP P450 system was inhibited by a 2 h pre-incubation in PB (100 μm). Flukes were then incubated for a further 22 h in NCTC medium containing either PB; PB+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nm); PB+NADPH+TCBZ (15 μg/ml); or PB+NADPH+TCBZ.SO (15 μg/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater disruption to the TCBZ-susceptible than the resistant isolate. However, co-incubation with PB and TCBZ/TCBZ.SO lead to more severe surface changes to the TCBZ-resistant Oberon isolate than with each drug on its own. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action, and only with TCBZ.SO. The results support the concept of altered drug metabolism in TCBZ-resistant flukes and this process may play a role in the development of drug resistance.
Fil: Devine, Catherine. The Queens University of Belfast; Irlanda
Fil: Brennan, Gerard P.. The Queens University of Belfast; Irlanda
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Trudgett, Alan G.. The Queens University of Belfast; Irlanda
Fil: Hoey, Elizabeth M.. The Queens University of Belfast; Irlanda
Fil: Fairweather, Ian. The Queens University of Belfast; Irlanda
Materia
FASCIOLA HEPATICA
LIVER FLUKE
TRICLABENDAZOLE RESISTANCE
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:11336/258630
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/258630
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazoleDevine, CatherineBrennan, Gerard P.Lanusse, Carlos EdmundoAlvarez, Luis IgnacioTrudgett, Alan G.Hoey, Elizabeth M.Fairweather, IanFASCIOLA HEPATICALIVER FLUKETRICLABENDAZOLE RESISTANCEhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP P450) system was inhibited using piperonyl butoxide (PB). The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP P450 system was inhibited by a 2 h pre-incubation in PB (100 μm). Flukes were then incubated for a further 22 h in NCTC medium containing either PB; PB+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nm); PB+NADPH+TCBZ (15 μg/ml); or PB+NADPH+TCBZ.SO (15 μg/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater disruption to the TCBZ-susceptible than the resistant isolate. However, co-incubation with PB and TCBZ/TCBZ.SO lead to more severe surface changes to the TCBZ-resistant Oberon isolate than with each drug on its own. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action, and only with TCBZ.SO. The results support the concept of altered drug metabolism in TCBZ-resistant flukes and this process may play a role in the development of drug resistance.Fil: Devine, Catherine. The Queens University of Belfast; IrlandaFil: Brennan, Gerard P.. The Queens University of Belfast; IrlandaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Trudgett, Alan G.. The Queens University of Belfast; IrlandaFil: Hoey, Elizabeth M.. The Queens University of Belfast; IrlandaFil: Fairweather, Ian. The Queens University of Belfast; IrlandaCambridge University Press2009-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/258630Devine, Catherine; Brennan, Gerard P.; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Trudgett, Alan G.; et al.; Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole; Cambridge University Press; Parasitology; 137; 5; 12-2009; 871-8800031-1820CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.cambridge.org/core/journals/parasitology/article/abs/inhibition-of-cytochrome-p450mediated-metabolism-enhances-ex-vivo-susceptibility-of-fasciola-hepatica-to-triclabendazole/0B1ADAA37D322BABA1CBDB9F64B9786Einfo:eu-repo/semantics/altIdentifier/doi/10.1017/S003118200999148Xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:05Zoai:ri.conicet.gov.ar:11336/258630instacron: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 10:00:05.258CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole
title Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole
spellingShingle Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole
Devine, Catherine
FASCIOLA HEPATICA
LIVER FLUKE
TRICLABENDAZOLE RESISTANCE
title_short Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole
title_full Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole
title_fullStr Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole
title_full_unstemmed Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole
title_sort Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole
dc.creator.none.fl_str_mv Devine, Catherine
Brennan, Gerard P.
Lanusse, Carlos Edmundo
Alvarez, Luis Ignacio
Trudgett, Alan G.
Hoey, Elizabeth M.
Fairweather, Ian
author Devine, Catherine
author_facet Devine, Catherine
Brennan, Gerard P.
Lanusse, Carlos Edmundo
Alvarez, Luis Ignacio
Trudgett, Alan G.
Hoey, Elizabeth M.
Fairweather, Ian
author_role author
author2 Brennan, Gerard P.
Lanusse, Carlos Edmundo
Alvarez, Luis Ignacio
Trudgett, Alan G.
Hoey, Elizabeth M.
Fairweather, Ian
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv FASCIOLA HEPATICA
LIVER FLUKE
TRICLABENDAZOLE RESISTANCE
topic FASCIOLA HEPATICA
LIVER FLUKE
TRICLABENDAZOLE RESISTANCE
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP P450) system was inhibited using piperonyl butoxide (PB). The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP P450 system was inhibited by a 2 h pre-incubation in PB (100 μm). Flukes were then incubated for a further 22 h in NCTC medium containing either PB; PB+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nm); PB+NADPH+TCBZ (15 μg/ml); or PB+NADPH+TCBZ.SO (15 μg/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater disruption to the TCBZ-susceptible than the resistant isolate. However, co-incubation with PB and TCBZ/TCBZ.SO lead to more severe surface changes to the TCBZ-resistant Oberon isolate than with each drug on its own. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action, and only with TCBZ.SO. The results support the concept of altered drug metabolism in TCBZ-resistant flukes and this process may play a role in the development of drug resistance.
Fil: Devine, Catherine. The Queens University of Belfast; Irlanda
Fil: Brennan, Gerard P.. The Queens University of Belfast; Irlanda
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
Fil: Trudgett, Alan G.. The Queens University of Belfast; Irlanda
Fil: Hoey, Elizabeth M.. The Queens University of Belfast; Irlanda
Fil: Fairweather, Ian. The Queens University of Belfast; Irlanda
description A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP P450) system was inhibited using piperonyl butoxide (PB). The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP P450 system was inhibited by a 2 h pre-incubation in PB (100 μm). Flukes were then incubated for a further 22 h in NCTC medium containing either PB; PB+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nm); PB+NADPH+TCBZ (15 μg/ml); or PB+NADPH+TCBZ.SO (15 μg/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater disruption to the TCBZ-susceptible than the resistant isolate. However, co-incubation with PB and TCBZ/TCBZ.SO lead to more severe surface changes to the TCBZ-resistant Oberon isolate than with each drug on its own. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action, and only with TCBZ.SO. The results support the concept of altered drug metabolism in TCBZ-resistant flukes and this process may play a role in the development of drug resistance.
publishDate 2009
dc.date.none.fl_str_mv 2009-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/258630
Devine, Catherine; Brennan, Gerard P.; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Trudgett, Alan G.; et al.; Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole; Cambridge University Press; Parasitology; 137; 5; 12-2009; 871-880
0031-1820
CONICET Digital
CONICET
url http://hdl.handle.net/11336/258630
identifier_str_mv Devine, Catherine; Brennan, Gerard P.; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Trudgett, Alan G.; et al.; Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole; Cambridge University Press; Parasitology; 137; 5; 12-2009; 871-880
0031-1820
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://www.cambridge.org/core/journals/parasitology/article/abs/inhibition-of-cytochrome-p450mediated-metabolism-enhances-ex-vivo-susceptibility-of-fasciola-hepatica-to-triclabendazole/0B1ADAA37D322BABA1CBDB9F64B9786E
info:eu-repo/semantics/altIdentifier/doi/10.1017/S003118200999148X
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
dc.publisher.none.fl_str_mv Cambridge University Press
publisher.none.fl_str_mv Cambridge University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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