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Ultrastructural changes to the tegumental system and the gastrodermal cells in adult Fasciola hepatica following in vivo treatment with the experimental fasciolicide, compound alpha

Published online by Cambridge University Press:  16 April 2009

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
A. FLANAGAN
Affiliation:
Parasite Proteomics and Therapeutics Research Group, Queens University Belfast
H. W. J. EDGAR
Affiliation:
Veterinary Sciences Division, Agri-Food Biosciences Institute (AFBI), Stormont, Belfast
R. CASTILLO
Affiliation:
Facultads de Quimica y Medicina Veterinaria, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City
A. HERNÁNDEZ-CAMPOS
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
*
*Corresponding author: Parasite Proteomics and Therapeutics Research Group, School of Biological Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland. Tel: +44 28 9097 2298. Fax: +44 28 9097 5877. E-mail: [email protected]

Summary

Sheep infected with the triclabendazole-susceptible, Cullompton isolate of Fasciola hepatica were dosed with 15 mg/kg of compound alpha at 12 weeks post-infection. Adult flukes were recovered from the bile ducts at 24, 48 and 72 h post-treatment (p.t.). Ultrastructural changes to the flukes were assessed using transmission electron microscopy (TEM), with a view to gathering information on the mechanism(s) of action for compound alpha and on the possible route of its entry into F. hepatica. The tegumental syncytium was more severely affected than the gut at all time-points p.t. with compound alpha, suggesting a predominantly trans-tegumental route of uptake. Disruption to the tegumental system became increasingly severe over time. A stress response was observed at 24 h p.t. and took the form of blebbing and increases in the production and transport of secretory bodies. By 72 h p.t., extensive tegumental loss and degeneration of the tegumental cell bodies had occurred. Degeneration of subtegumental tissues and internal flooding were also observed. Changes in the gastrodermal cells were slow to develop: reduced secretory activity was evident at 72 h p.t.. There was progressive disruption to the somatic muscle layers, with disorganization of the muscle blocks and loss of muscle fibres.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2009

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References

REFERENCES

Anderson, H. R. and Fairweather, I. (1995). Fasciola hepatica: ultrastructural changes to the tegument of juvenile flukes following incubation in vitro with the deacetylated (amine) metabolite of diamphenethide. International Journal for Parasitology 25, 319333.CrossRefGoogle Scholar
Buchanan, J. F., Fairweather, I., Brennan, G., Trudgett, A. and Hoey, E. M. (2003). Fasciola hepatica: surface and internal tegumental changes induced by treatment in vitro with the sulphoxide metabolite of albendazole (‘Valbazen’). Parasitology 126, 141153.CrossRefGoogle ScholarPubMed
Carr, A. W., McCracken, R. O. and Stillwell, W. H. (1993). Uncoupling of rat liver mitochondria oxidative phosphorylation by the fasciolicide triclabendazole and its sulfoxide and sulfone metabolites. Journal of Parasitology 79, 198204.CrossRefGoogle ScholarPubMed
Fairweather, I. and Boray, J. C. (1999). Fasciolicides: efficacy, actions, resistance and its management. Veterinary Journal 158, 81–112.CrossRefGoogle ScholarPubMed
Fairweather, I., Holmes, S. D. and Threadgold, L. T. (1984). Fasciola hepatica: motility response to fasciolicides in vitro. Experimental Parasitology 57, 209224.CrossRefGoogle ScholarPubMed
Fairweather, I., Anderson, H. R. and Threadgold, L. T. (1986) Fasciola hepatica: tegumental changes induced in vitro by the deacetylated (amine) metabolite of diamphenethide. Experimental Parasitology 62, 336348.CrossRefGoogle ScholarPubMed
Fairweather, I., Anderson, H. R. and Baldwin, T. M. A. (1987). Fasciola hepatica: tegumental surface alterations following treatment in vitro with the deacetylated (amine) metabolite of diamphenethide. Parasitology Research 73, 99–106.CrossRefGoogle ScholarPubMed
Fairweather, I., Threadgold, L. T. and Hanna, R. E. B. (1999). Development of Fasciola hepatica in the mammalian host. In Fasciolosis (ed. Dalton, J. P.), pp. 47–111. CAB International Publishing, Oxon, UK.Google Scholar
Halferty, L., Brennan, G. P., Hanna, R. E. B., Edgar, H. W., Meaney, M., McConville, M., Trudgett, A., Hoey, L. and Fairweather, I. (2008). Tegumental surface changes in juvenile Fasciola hepatica in response to treatment in vivo with triclabendazole. Veterinary Parasitology 155, 4958.CrossRefGoogle ScholarPubMed
Hanna, R. E. B. (1980). Fasciola hepatica: glycocalyx replacement in the juvenile as a possible mechanism for protection against host immunity. Experimental Parasitology 50, 103114.CrossRefGoogle ScholarPubMed
Hernández-Campos, A., Ibarra-Velarde, F., Vera-Montenegro, Y., Rivera-Fernandez, N. and Castillo, R. (2002). Synthesis and fasciolicidal activity of 5-chloro-2-methylthio-6-(1-naphthyloxy)-1H-benzimidazole. Chemical and Pharmaceutical Bulletin 50, 649652.CrossRefGoogle ScholarPubMed
Heytler, P. G. (1979). Uncouplers of oxidative phosphorylation. Methods in Enzymology 55, 462472.CrossRefGoogle ScholarPubMed
Ibarra, V. F., García, S. E., Fernández, R. M., Vera, M. Y., Castillo, B. R. and Hernández, C. A. (1997 a). Eficacia fasciolicida de dos compuestos de síntesis química in vitro e in vivo en ovinos. Veterinaria México 8, 48.Google Scholar
Ibarra, V. F., Vera, M. Y., Hernández, C. A. and Castillo, B. R. (1997 b). Eficacia fasciolicida del compuesto “alfa” contra estadios juveniles y adultos en ovinos. Veterinaria México 28, 297301.Google Scholar
Ibarra, V. F., Montenegro, C. N., Flores, C. J., Hernández, C. A. and Castillo, B. R. (2000). Evaluación de cuatro vehículos para formular un fasciolicida experimental. Veterinaria México 31, 4751.Google Scholar
Kelly, R. B. (1990). Microtubules, membrane traffic, and cell organisation. Cell 61, 57.CrossRefGoogle Scholar
Kumar, D., McGeown, J. G., Reynoso-Ducoing, O., Ambrosio, J. R. and Fairweather, I. (2003). Observations on the musculature and isolated muscle fibres of the liver fluke, Fasciola hepatica. Parasitology 127, 457473.CrossRefGoogle ScholarPubMed
McCoy, M. A., Fairweather, I., Brennan, G. P., Kenny, J. M., Ellison, S. and Forbes, A. F. (2005). The efficacy of nitroxynil and triclabendazole administered synchronously against juvenile triclabendazole-resistant Fasciola hepatica in sheep. Research in Veterinary Science 78 (Suppl. A), 33.Google Scholar
McConville, M., Brennan, G. P., McCoy, M., Castillo, R., Hernandez-Campos, A., Ibarra, F. and Fairweather, I. (2006). Adult triclabendazole-resistant Fasciola hepatica: surface and subsurface tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha. Parasitology 133, 195208.CrossRefGoogle ScholarPubMed
McConville, M., Brennan, G. P., McCoy, M., Castillo, R., Hernandez-Campos, A., Ibarra, F. and Fairweather, I. (2007). Immature triclabendazole-resistant Fasciola hepatica: tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha. Parasitology Research 100, 365377.CrossRefGoogle ScholarPubMed
McConville, M., Brennan, G. P., Flanagan, A., Edgar, H. W. J., McCoy, M., Castillo, R., Hernández-Campos, A. and Fairweather, I. (2008). Surface and internal tegumental changes in juvenile Fasciola hepatica following treatment in vivo with the experimental fasciolicide, compound alpha. Veterinary Parasitology 153, 5264.CrossRefGoogle ScholarPubMed
McConville, M., Brennan, G. P., Flanagan, A., Edgar, H. W. J., Hanna, R. E. B., McCoy, M., Gordon, A. W., Castillo, R., Hernández-Campos, A. and Fairweather, I. (2009). An evaluation of the efficacy of compound alpha and triclabendazole against two isolates of Fasciola hepatica. Veterinary Parasitology (in the Press).CrossRefGoogle ScholarPubMed
McKinstry, B., Fairweather, I., Brennan, G. P. and Forbes, A. B. (2003). Fasciola hepatica: tegumental surface alterations following treatment in vivo and in vitro with nitroxynil (Trodax). Parasitology Research 91, 251263.CrossRefGoogle ScholarPubMed
McKinstry, B., Brennan, G. P., Halferty, L., Forbes, A. B. and Fairweather, I. (2007). Ultrastructural changes induced in the tegument and gut of Fasciola hepatica following in vivo and in vitro drug treatment with nitroxynil (Trodax). Parasitology Research 101, 929941.CrossRefGoogle ScholarPubMed
McKinstry, B., Halferty, L., Brennan, G. P. and Fairweather, I. (2009). Morphological response of triclabendazole-susceptible and triclabendazole-resistant isolates of Fasciola hepatica to treatment in vitro with nitroxynil (Trodax). Parasitology Research 104, 645655.CrossRefGoogle ScholarPubMed
Meaney, M., Fairweather, I., Brennan, G. P., McDowell, L. S. L. and Forbes, A. B. (2003). Fasciola hepatica: effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes. Parasitology Research 91, 238250.CrossRefGoogle Scholar
Meaney, M., Fairweather, I., Brennan, G. and Forbes, A. B. (2004). Transmission electron microscope study of the ultrastructural changes induced in the tegument and gut of Fasciola hepatica following treatment with clorsulon. Parasitology Research 92, 232241.CrossRefGoogle ScholarPubMed
Meaney, M., Haughey, S., Brennan, G. P. and Fairweather, I. (2005 a). A scanning electron microscope study on the route of entry of clorsulon into the liver fluke, Fasciola hepatica. Parasitology Research 95, 117128 and 96, 189–198.CrossRefGoogle Scholar
Meaney, M., Haughey, S., Brennan, G. P. and Fairweather, I. (2005 b). Ultrastructural observations on oral ingestion and trans-tegumental uptake of clorsulon by the liver fluke, Fasciola hepatica. Parasitology Research 95, 201212.CrossRefGoogle ScholarPubMed
Meaney, M., Allister, J., McKinstry, B., McLaughlin, K., Brennan, G. P., Forbes, A. B. and Fairweather, I. (2007). Fasciola hepatica: ultrastructural effects of a combination of triclabendazole and clorsulon against mature fluke. Parasitology Research 100, 10911104.CrossRefGoogle ScholarPubMed
Mottier, L., Alverez, L., Ceballos, L. and Lanusse, C. (2006). Drug transport mechanisms in helminth parasites: passive diffusion of benzimidazole anthelmintics. Experimental Parasitology 113, 4957.CrossRefGoogle ScholarPubMed
Ramírez, N., Mayet, L., Del Rivero, L., Ibarra-Velarde, F., Castillo, R., Hernández-Campos, A. and Jung-Cook, H. (2009). Pharmacokinetic behaviour in sheep and cattle of 5-Chloro-2-(methylthio)-6-(1-naphthyloxy)-1H-benzimidazole, a new fasciolicide agent. Journal of Veterinary Pharmacology and Therapeutics (in the Press).CrossRefGoogle ScholarPubMed
Rivera, F. N., Ibarra, V. F., Olazaràn, J. S., Vera, M. Y., Castillo, B. R. and Hernández, C. A. (2002). Efficacy of 5-chloro-2-methylthio-6-(1-naftiloxi)-ih-benzimidazole against different stages of Fasciola hepatica in Pelibuey sheep. Veterinaria México 33, 5561.Google Scholar
Rivera, N., Ibarra, F., Zepeda, A., Fortoul, T., Cantó, G., Hernández, A. and Castillo, R. (2005). The effect of the 5-chloro-2-methylthio-6-(1-naphtyloxy)-H-benzimidazole on the tegument of immature Fasciola hepatica in their natural host. Parasitology Research 95, 379383.CrossRefGoogle Scholar
Rivera, N., Ibarra, F., Zepeda, A., Fortoul, T., Hernández, A., Castillo, R. and Cantó, G. (2004). Tegumental surface changes in adult Fasciola hepatica following treatment in vitro and in vivo with an experimental fasciolicide. Parasitology Research 93, 283286.CrossRefGoogle ScholarPubMed
Rivero, L. M., Jung, H., Castillo, R. and Hernández Campos, A. (1998). High-performance liquid chromatographic assay for a new fasciolicide agent, α-BIOF10, in biological fluids. Journal of Chromatography B 712, 237241.CrossRefGoogle ScholarPubMed
Robinson, G. and Threadgold, L. T. (1975). Electron microscope studies of Fasciola hepatica. XII. The fine structure of the gastrodermis. Experimental Parasitology 37, 2036.CrossRefGoogle ScholarPubMed
Robinson, M. W., Trudgett, A., Hoey, E. M. and Fairweather, I. (2002). Triclabendazole-resistant Fasciola hepatica: ß-tubulin and response to in vitro treatment with triclabendazole. Parasitology 124, 325338.CrossRefGoogle Scholar
Robinson, M. W., Trudgett, A., Hoey, E. M. and Fairweather, I. (2003). The effect of the microtubule inhibitor tubulozole-C on the tegument of triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica. Parasitology Research 91, 117129.CrossRefGoogle ScholarPubMed
Skuce, P. J. and Fairweather, I. (1990). The effect of the hydrogen ionophore closantel upon the pharmacology and ultrastructure of the adult liver fluke Fasciola hepatica. Parasitology Research 76, 241250.CrossRefGoogle ScholarPubMed
Stitt, A. W. and Fairweather, I. (1993 a). Fasciola hepatica: tegumental surface changes in adult and juvenile flukes following treatment in vitro with the sulphoxide metabolite of triclabendazole (‘Fasinex’). Parasitology Research 79, 529536.CrossRefGoogle ScholarPubMed
Stitt, A. W. and Fairweather, I. (1993 b). Fasciola hepatica: the effect of the microtubule inhibitors colchicine and tubulozole-C on the ultrastructure of the adult fluke. Parasitology 107, 297309.CrossRefGoogle ScholarPubMed
Stitt, A. W. and Fairweather, I. (1994). The effect of the sulphoxide metabolite of triclabendazole (‘Fasinex’) on the tegument of mature and immature stages of the liver fluke, Fasciola hepatica. Parasitology 108, 555567.CrossRefGoogle ScholarPubMed
Threadgold, L. T. and Brennan, G. (1978). Fasciola hepatica: basal infolds and associated vacuoles of the tegument. Experimental Parasitology 46, 300316.CrossRefGoogle ScholarPubMed
Toner, E., McConvery, F., Meaney, M., Brennan, G. P. and Fairweather, I. (2009). A scanning electron microscope study on the route of entry of triclabendazole into the liver fluke, Fasciola hepatica. Parasitology 136 (in Press).CrossRefGoogle Scholar
Verheyen, A., Vanparijs, O., Lauwers, H. and Thienpont, D. (1980). The influence of closantel administration to sheep on the ultrastructure of the adult liver fluke, Fasciola hepatica L. In The Host-Invader Interplay (ed. Van den Bossche, H.), pp. 705708. Elsevier/North Holland, Amsterdam, The Netherlands.Google Scholar
Walker, S. M., McKinstry, B., Boray, J. C., Brennan, G. P., Trudgett, A., Hoey, E. M., Fletcher, H. and Fairweather, I. (2004). Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro. Parasitology Research 94, 427438.CrossRefGoogle ScholarPubMed