Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep

Autores
Moreno Torrejon, Laura; Ceballos, Laura; Fairweather, Ian; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The flukicidal compound triclabendazole (TCBZ) has a complex metabolic pattern that includes the systemic presence of its sulphoxide (TCBZ.SO) and sulphone (TCBZ.SO2) metabolites, usually recovered from the bile of treated animals. The aim of the current work was to evaluate the time-course and pattern of in vivo accumulation of TCBZ/metabolites into adult Fasciola hepatica specimens recovered from infected sheep. Twelve (12) healthy Corriedale sheep were orally infected with one hundred (100) metacercariae of the TCBZ-susceptible Cullomptom isolate of F. hepatica. Sixteen weeks after infection, animals were intraruminally treated with TCBZ (10 mg/kg). At 3, 24, 48 and 60 h post-treatment (pt), animals were sacrificed (n = 3/time period) and samples of blood, bile, liver tissue and adult F. hepatica specimens were collected. The concentrations of TCBZ/metabolites were measured by HPLC. TCBZ.SO and TCBZ.SO2 were the only molecules recovered in the bloodstream, with peak plasma concentrations of 10.8 lg/mL (TCBZ.SO) and 12.6 lg/mL (TCBZ.SO2). The same metabolites were also the main analytes accumulated within the adult flukes, reaching peak concentrations between 6.35 lg/g (TCBZ.SO) and 13.9 lg/g (TCBZ.SO2) at 24 h pt, which was coincident with the time when the maximum plasma concentration was attained. Low levels of TCBZ parent drug (0.14 lg/g at 24 h pt) were measured within collected flukes. TCBZ parent drug and its sulpho- and hydroxy-derivatives were recovered in bile collected from treated sheep between 3 and 60 h pt. Although relatively high concentrations of hydroxy-TCBZ (ranging from 0.86 to 10.1 lg/mL) were measured in bile, this metabolite was not recovered within the flukes at any time pt. Finally, TCBZ parent drug was the main compound accumulated in liver tissue over the 60 h pt period. The time-course and drug concentration patterns within the adult liver fluke after TCBZ treatment followed a similar trend to those observed in plasma. Overall, the data reported here confirm that oral ingestion is a main route of drug entry into the trematode in vivo exposed to TCBZ/metabolites.
Fil: Moreno Torrejon, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina
Fil: Fairweather, Ian. The Queens University Of Belfast; Irlanda
Fil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina
Materia
Triclabendazole
Fasciola Hepatica
Drug Distribution
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/10797

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network_name_str CONICET Digital (CONICET)
spelling Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheepMoreno Torrejon, LauraCeballos, LauraFairweather, IanLanusse, Carlos EdmundoAlvarez, Luis IgnacioTriclabendazoleFasciola HepaticaDrug Distributionhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4The flukicidal compound triclabendazole (TCBZ) has a complex metabolic pattern that includes the systemic presence of its sulphoxide (TCBZ.SO) and sulphone (TCBZ.SO2) metabolites, usually recovered from the bile of treated animals. The aim of the current work was to evaluate the time-course and pattern of in vivo accumulation of TCBZ/metabolites into adult Fasciola hepatica specimens recovered from infected sheep. Twelve (12) healthy Corriedale sheep were orally infected with one hundred (100) metacercariae of the TCBZ-susceptible Cullomptom isolate of F. hepatica. Sixteen weeks after infection, animals were intraruminally treated with TCBZ (10 mg/kg). At 3, 24, 48 and 60 h post-treatment (pt), animals were sacrificed (n = 3/time period) and samples of blood, bile, liver tissue and adult F. hepatica specimens were collected. The concentrations of TCBZ/metabolites were measured by HPLC. TCBZ.SO and TCBZ.SO2 were the only molecules recovered in the bloodstream, with peak plasma concentrations of 10.8 lg/mL (TCBZ.SO) and 12.6 lg/mL (TCBZ.SO2). The same metabolites were also the main analytes accumulated within the adult flukes, reaching peak concentrations between 6.35 lg/g (TCBZ.SO) and 13.9 lg/g (TCBZ.SO2) at 24 h pt, which was coincident with the time when the maximum plasma concentration was attained. Low levels of TCBZ parent drug (0.14 lg/g at 24 h pt) were measured within collected flukes. TCBZ parent drug and its sulpho- and hydroxy-derivatives were recovered in bile collected from treated sheep between 3 and 60 h pt. Although relatively high concentrations of hydroxy-TCBZ (ranging from 0.86 to 10.1 lg/mL) were measured in bile, this metabolite was not recovered within the flukes at any time pt. Finally, TCBZ parent drug was the main compound accumulated in liver tissue over the 60 h pt period. The time-course and drug concentration patterns within the adult liver fluke after TCBZ treatment followed a similar trend to those observed in plasma. Overall, the data reported here confirm that oral ingestion is a main route of drug entry into the trematode in vivo exposed to TCBZ/metabolites.Fil: Moreno Torrejon, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Fairweather, Ian. The Queens University Of Belfast; IrlandaFil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; ArgentinaFil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaElsevier2014-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/10797Moreno Torrejon, Laura; Ceballos, Laura; Fairweather, Ian; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep; Elsevier; Experimental Parasitology; 136; 2-2014; 14-190014-4894enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2013.10.014info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014489413002865info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:44:08Zoai:ri.conicet.gov.ar:11336/10797instacron: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:34982025-10-15 14:44:08.47CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep
title Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep
spellingShingle Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep
Moreno Torrejon, Laura
Triclabendazole
Fasciola Hepatica
Drug Distribution
title_short Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep
title_full Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep
title_fullStr Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep
title_full_unstemmed Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep
title_sort Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep
dc.creator.none.fl_str_mv Moreno Torrejon, Laura
Ceballos, Laura
Fairweather, Ian
Lanusse, Carlos Edmundo
Alvarez, Luis Ignacio
author Moreno Torrejon, Laura
author_facet Moreno Torrejon, Laura
Ceballos, Laura
Fairweather, Ian
Lanusse, Carlos Edmundo
Alvarez, Luis Ignacio
author_role author
author2 Ceballos, Laura
Fairweather, Ian
Lanusse, Carlos Edmundo
Alvarez, Luis Ignacio
author2_role author
author
author
author
dc.subject.none.fl_str_mv Triclabendazole
Fasciola Hepatica
Drug Distribution
topic Triclabendazole
Fasciola Hepatica
Drug Distribution
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 flukicidal compound triclabendazole (TCBZ) has a complex metabolic pattern that includes the systemic presence of its sulphoxide (TCBZ.SO) and sulphone (TCBZ.SO2) metabolites, usually recovered from the bile of treated animals. The aim of the current work was to evaluate the time-course and pattern of in vivo accumulation of TCBZ/metabolites into adult Fasciola hepatica specimens recovered from infected sheep. Twelve (12) healthy Corriedale sheep were orally infected with one hundred (100) metacercariae of the TCBZ-susceptible Cullomptom isolate of F. hepatica. Sixteen weeks after infection, animals were intraruminally treated with TCBZ (10 mg/kg). At 3, 24, 48 and 60 h post-treatment (pt), animals were sacrificed (n = 3/time period) and samples of blood, bile, liver tissue and adult F. hepatica specimens were collected. The concentrations of TCBZ/metabolites were measured by HPLC. TCBZ.SO and TCBZ.SO2 were the only molecules recovered in the bloodstream, with peak plasma concentrations of 10.8 lg/mL (TCBZ.SO) and 12.6 lg/mL (TCBZ.SO2). The same metabolites were also the main analytes accumulated within the adult flukes, reaching peak concentrations between 6.35 lg/g (TCBZ.SO) and 13.9 lg/g (TCBZ.SO2) at 24 h pt, which was coincident with the time when the maximum plasma concentration was attained. Low levels of TCBZ parent drug (0.14 lg/g at 24 h pt) were measured within collected flukes. TCBZ parent drug and its sulpho- and hydroxy-derivatives were recovered in bile collected from treated sheep between 3 and 60 h pt. Although relatively high concentrations of hydroxy-TCBZ (ranging from 0.86 to 10.1 lg/mL) were measured in bile, this metabolite was not recovered within the flukes at any time pt. Finally, TCBZ parent drug was the main compound accumulated in liver tissue over the 60 h pt period. The time-course and drug concentration patterns within the adult liver fluke after TCBZ treatment followed a similar trend to those observed in plasma. Overall, the data reported here confirm that oral ingestion is a main route of drug entry into the trematode in vivo exposed to TCBZ/metabolites.
Fil: Moreno Torrejon, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina
Fil: Fairweather, Ian. The Queens University Of Belfast; Irlanda
Fil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina
Fil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigacion Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires; Argentina
description The flukicidal compound triclabendazole (TCBZ) has a complex metabolic pattern that includes the systemic presence of its sulphoxide (TCBZ.SO) and sulphone (TCBZ.SO2) metabolites, usually recovered from the bile of treated animals. The aim of the current work was to evaluate the time-course and pattern of in vivo accumulation of TCBZ/metabolites into adult Fasciola hepatica specimens recovered from infected sheep. Twelve (12) healthy Corriedale sheep were orally infected with one hundred (100) metacercariae of the TCBZ-susceptible Cullomptom isolate of F. hepatica. Sixteen weeks after infection, animals were intraruminally treated with TCBZ (10 mg/kg). At 3, 24, 48 and 60 h post-treatment (pt), animals were sacrificed (n = 3/time period) and samples of blood, bile, liver tissue and adult F. hepatica specimens were collected. The concentrations of TCBZ/metabolites were measured by HPLC. TCBZ.SO and TCBZ.SO2 were the only molecules recovered in the bloodstream, with peak plasma concentrations of 10.8 lg/mL (TCBZ.SO) and 12.6 lg/mL (TCBZ.SO2). The same metabolites were also the main analytes accumulated within the adult flukes, reaching peak concentrations between 6.35 lg/g (TCBZ.SO) and 13.9 lg/g (TCBZ.SO2) at 24 h pt, which was coincident with the time when the maximum plasma concentration was attained. Low levels of TCBZ parent drug (0.14 lg/g at 24 h pt) were measured within collected flukes. TCBZ parent drug and its sulpho- and hydroxy-derivatives were recovered in bile collected from treated sheep between 3 and 60 h pt. Although relatively high concentrations of hydroxy-TCBZ (ranging from 0.86 to 10.1 lg/mL) were measured in bile, this metabolite was not recovered within the flukes at any time pt. Finally, TCBZ parent drug was the main compound accumulated in liver tissue over the 60 h pt period. The time-course and drug concentration patterns within the adult liver fluke after TCBZ treatment followed a similar trend to those observed in plasma. Overall, the data reported here confirm that oral ingestion is a main route of drug entry into the trematode in vivo exposed to TCBZ/metabolites.
publishDate 2014
dc.date.none.fl_str_mv 2014-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/10797
Moreno Torrejon, Laura; Ceballos, Laura; Fairweather, Ian; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep; Elsevier; Experimental Parasitology; 136; 2-2014; 14-19
0014-4894
url http://hdl.handle.net/11336/10797
identifier_str_mv Moreno Torrejon, Laura; Ceballos, Laura; Fairweather, Ian; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep; Elsevier; Experimental Parasitology; 136; 2-2014; 14-19
0014-4894
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language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2013.10.014
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014489413002865
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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