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dc.contributor.author
Devine, C.  
dc.contributor.author
Brennan, G.P.  
dc.contributor.author
Lanusse, Carlos Edmundo  
dc.contributor.author
Alvarez, Luis Ignacio  
dc.contributor.author
Trudgett, A.  
dc.contributor.author
Hoey, E.  
dc.contributor.author
Fairweather, I.  
dc.date.available
2019-02-25T21:06:37Z  
dc.date.issued
2011-10  
dc.identifier.citation
Devine, C.; Brennan, G.P.; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Trudgett, A.; et al.; Inhibition of triclabendazole metabolism in vitro by ketoconazole increases disruption to the tegument of a triclabendazole-resistant isolate of Fasciola hepatica; Springer; Parasitology Research; 109; 4; 10-2011; 981-995  
dc.identifier.issn
0932-0113  
dc.identifier.uri
http://hdl.handle.net/11336/70820  
dc.description.abstract
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 450) enzyme pathway was inhibited using ketoconazole (KTZ) to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ action. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP 450 system was inhibited by a 2-h pre-incubation in ketoconazole (40 μM), 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). Changes to fluke ultrastructure following drug treatment and metabolic inhibition were assessed using transmission electron microscopy. After treatment with either TCBZ or TCBZ.SO on their own, there was greater disruption to the TCBZ-susceptible than TCBZ-resistant isolate. However, co-incubation with KTZ+ TCBZ, but more particularly KTZ+TCBZ.SO, led to more severe changes to the TCBZ-resistant isolate than with each drug on its own: in the syncytium, for example, there was severe swelling of the basal infolds and their associated mucopolysaccharide masses, accompanied by an accumulation of secretory bodies just below the apex. Golgi complexes were greatly reduced or absent in the tegumental cells and the synthesis, production, and transport of secretory bodies were badly disrupted. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action. 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.  
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
Triclabendazole  
dc.subject
In Vitro  
dc.subject
Ketoconazole  
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Fasciola Hepatica  
dc.subject.classification
Ciencias Veterinarias  
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Ciencias Veterinarias  
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CIENCIAS AGRÍCOLAS  
dc.title
Inhibition of triclabendazole metabolism in vitro by ketoconazole increases disruption to the tegument of a triclabendazole-resistant isolate of Fasciola hepatica  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2019-01-23T18:54:34Z  
dc.identifier.eissn
1432-1955  
dc.journal.volume
109  
dc.journal.number
4  
dc.journal.pagination
981-995  
dc.journal.pais
Alemania  
dc.journal.ciudad
Berlin  
dc.description.fil
Fil: Devine, C.. The Queens University of Belfast; Irlanda  
dc.description.fil
Fil: Brennan, G.P.. The Queens University of Belfast; Irlanda  
dc.description.fil
Fil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Alvarez, Luis Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Trudgett, A.. The Queens University of Belfast; Irlanda  
dc.description.fil
Fil: Hoey, E.. The Queens University of Belfast; Irlanda  
dc.description.fil
Fil: Fairweather, I.. 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/s00436-011-2304-9  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00436-011-2304-9