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dc.contributor.author
Devine, Catherine  
dc.contributor.author
Brennan, Gerard P.  
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Lanusse, Carlos Edmundo  
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Alvarez, Luis Ignacio  
dc.contributor.author
Trudgett, Alan  
dc.contributor.author
Hoey, Elizabeth  
dc.contributor.author
Fairweather, Ian  
dc.date.available
2019-09-18T20:01:30Z  
dc.date.issued
2010-07  
dc.identifier.citation
Devine, Catherine; Brennan, Gerard P.; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Trudgett, Alan; et al.; Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole; Springer; Parasitology Research; 107; 2; 7-2010; 337-353  
dc.identifier.issn
0932-0113  
dc.identifier.uri
http://hdl.handle.net/11336/83877  
dc.description.abstract
A study has been carried out to investigate whether the action of triclabendazole (TCBZ) is altered by using the metabolic inhibitor, ketoconazole (KTZ) to inhibit the cytochrome P450 (CYP 450) system within Fasciola hepatica. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP 450 enzyme system was inhibited by a 2 h pre-incubation in KTZ (40 μM). Flukes were then incubated for a further 22 h in NCTC medium containing either KTZ; KTZ + nicotinamide adenine dinucleotide phosphate (NADPH; 1 nM); KTZ + NADPH + TCBZ (15 μg/ml); or KTZ + NADPH + triclabendazole sulphoxide (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 isolate than the TCBZ-resistant isolate. However, co-incubation with KTZ and TCBZ/TCBZ.SO led to more severe surface changes to the TCBZ-resistant isolate than with each drug on its own, with greater swelling and blebbing of the tegument and even the loss of the apical plasma membrane in places. With the Cullompton isolate, there was limited potentiation of drug action in combination with KTZ, and only with TCBZ.SO. The results support the concept of altered drug metabolism within TCBZ-resistant isolates and indicate that this process may play a role in the development of drug resistance.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Springer  
dc.rights
info:eu-repo/semantics/restrictedAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Fasciola  
dc.subject
Hepatica  
dc.subject
Metabolic  
dc.subject
Ketoconazole  
dc.subject.classification
Ciencias Veterinarias  
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Ciencias Veterinarias  
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CIENCIAS AGRÍCOLAS  
dc.title
Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2019-07-24T17:37:43Z  
dc.journal.volume
107  
dc.journal.number
2  
dc.journal.pagination
337-353  
dc.journal.pais
Alemania  
dc.journal.ciudad
Berlin  
dc.description.fil
Fil: Devine, Catherine. The Queens University of Belfast; Irlanda  
dc.description.fil
Fil: Brennan, Gerard P.. The Queens University of Belfast; Irlanda  
dc.description.fil
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  
dc.description.fil
Fil: Alvarez, Luis Ignacio. 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  
dc.description.fil
Fil: Trudgett, Alan. The Queens University of Belfast; Irlanda  
dc.description.fil
Fil: Hoey, Elizabeth. The Queens University of Belfast; Irlanda  
dc.description.fil
Fil: Fairweather, Ian. The Queens University of Belfast; Irlanda  
dc.journal.title
Parasitology Research  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00436-010-1866-2  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00436-010-1866-2