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dc.contributor.author
Devine, Catherine
dc.contributor.author
Brennan, Gerard P.
dc.contributor.author
Lanusse, Carlos Edmundo
dc.contributor.author
Alvarez, Luis Ignacio
dc.contributor.author
Trudgett, Alan
dc.contributor.author
Hoey, Elizabeth
dc.contributor.author
Fairweather, Ian
dc.date.available
2019-09-18T20:31:27Z
dc.date.issued
2010-05
dc.identifier.citation
Devine, Catherine; Brennan, Gerard P.; Lanusse, Carlos Edmundo; Alvarez, Luis Ignacio; Trudgett, Alan; et al.; Potentiation of triclabendazole sulphoxide-induced tegumental disruption by methimazole in a triclabendazole-resistant isolate of Fasciola hepatica; Springer; Parasitology Research; 106; 6; 5-2010; 1351-1363
dc.identifier.issn
0932-0113
dc.identifier.uri
http://hdl.handle.net/11336/83887
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 flavin monooxygenase system (FMO) was inhibited using methimazole (MTZ) 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 FMO system was inhibited by a 2-h pre-incubation in methimazole (100 μM), then incubated for a further 22 h in NCTC medium containing either MTZ; MTZ+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nM); MTZ+NADPH+TCBZ (15 μg/ml); or MTZ+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 triclabedazole-resistant isolate. However, co-incubation with MTZ+TCBZ, but more particularly MTZ+TCBZ.SO, led to more severe changes to the TCBZ-resistant isolate than with each drug on its own, with severe swelling of the basal infolds and mucopolysaccharide masses in the syncytium, accompanied by a reduction in numbers of secretory bodies. The synthesis and production of secretory bodies in the tegumental cells was severely affected as well. 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
Methimazole
dc.subject
Fasciola
dc.subject
Hepatica
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Ciencias Veterinarias
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Ciencias Veterinarias
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CIENCIAS AGRÍCOLAS
dc.title
Potentiation of triclabendazole sulphoxide-induced tegumental disruption by methimazole in 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
2019-07-24T17:38:24Z
dc.journal.volume
106
dc.journal.number
6
dc.journal.pagination
1351-1363
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; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina
dc.description.fil
Fil: Alvarez, Luis Ignacio. 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
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/url/https://link.springer.com/article/10.1007/s00436-010-1806-1
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1007/s00436-010-1806-1
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