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Adult triclabendazole-resistant Fasciola hepatica: surface and subsurface tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha

Published online by Cambridge University Press:  02 May 2006

M. McCONVILLE ,
G. P. BRENNAN ,
M. McCOY ,
R. CASTILLO ,
A. HERNANDEZ-CAMPOS ,
F. IBARRA  and
I. FAIRWEATHER
M. McCONVILLE
Affiliation:
Parasite Proteomics and Therapeutics Research Group, Queens University Belfast
G. P. BRENNAN
Affiliation:
Parasite Proteomics and Therapeutics Research Group, Queens University Belfast
M. McCOY
Affiliation:
Veterinary Sciences Division, Department of Agriculture and Rural Development for Northern Ireland (DARDNI), Belfast
R. CASTILLO
Affiliation:
Facultads de Quimica y Medicina Veterinaria, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City
A. HERNANDEZ-CAMPOS
Affiliation:
Facultads de Quimica y Medicina Veterinaria, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City
F. IBARRA
Affiliation:
Facultads de Quimica y Medicina Veterinaria, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City
I. FAIRWEATHER
Affiliation:
Parasite Proteomics and Therapeutics Research Group, Queens University Belfast
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Abstract

Mature Fasciola hepatica of the triclabendazole-resistant Sligo isolate were incubated in vitro with 10 μg/ml of the sulphoxide metabolite of compound alpha [5-chloro-2-methylthio-6-(1-naphthyloxy)-H-benzimidazole]; the metabolite will be referred to as alpha.SO. Changes resulting from drug treatment were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and tubulin immunocytochemistry (ICC). SEM revealed that disruption to the tegumental surface mainly took the form of swelling and blebbing. Extensive spine loss occurred on the ventral surface of the oral cone, and sloughing of the tegument was observed along the lateral margins of the fluke. Examination of sections from the anterior mid-body region at the TEM level revealed that treatment with alpha.SO led to swelling of the basal infolds and mitochondria within the tegumental syncytium; also, accumulations of secretory bodies beneath the apical plasma membrane. The tegumental cell bodies contained swollen mitochondria and cisternae of granular endoplasmic reticulum, but few Golgi complexes were observed. An increase in T2 secretory bodies was observed, whilst in the T1 tegumental cells, the T1 secretory bodies had decreased in number. Immunocytochemical (ICC) studies showed that incubation with alpha.SO, ABZ.SO and TCBZ.SO did not cause significant changes to the distribution of tubulin within the tegumental syncytium of the Sligo isolate. In contrast, alpha.SO, ABZ.SO and TCBZ.SO caused severe disruption to tubulin organization within the syncytial layer of the TCBZ-susceptible Cullompton isolate. The EM results confirm that compound alpha is a fasciolicide capable of disrupting the tegument of mature TCBZ-resistant F. hepatica; however, this was not accompanied by any change in tubulin immunoreactivity.

Keywords

Fasciola hepaticatriclabendazole resistancealpha.SOimmunocytochemistrytegumenttubulin
Type
Research Article
Information
Parasitology , Volume 133 , Issue 2 , August 2006 , pp. 195 - 208
Copyright
2006 Cambridge University Press

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