Fasciola hepatica: Tegumental surface changes in adult and juvenile flukes following treatment in vitro with the sulphoxide metabolite of triclabendazole (Fasinex)

Paramphistomosis is a chronic, debilitating parasitic disease of livestock prevalent in the tropical and sub-tropical countries. Globally there is a heavy reliance on anthelmintics but concerns over drug resistance encourage the search for new leads. Metalloproteinases play a significant role in the biology and life cycle of parasitic helminths. The efficacy of metalloproteinase inhibitor, 1,10-Phenanthroline (1,10-phe) which is commonly used as a specific enzyme inhibitor in biochemical assays, was tested in vitro on Gigantocotyle explanatum tegument as a marker of anthelmintic action. The scanning electron microscopy revealed that the tegumental surface exhibited considerable changes in the worms treated with the metalloenzyme inhibitor, 1,10-phe. The untreated control worms appeared normal showing smooth tegumental surface with abundant dome shaped papillae in the anterior to mid region, while their density was less around the acetabulum which serves as a hold-fast organ helping the worms to remain attached in biliary passage. The 1,10-phe produced significant tegumental damage when the liver amphistomes were in vitro exposed to this compound at 12.5 µM concentration. The surface changes appeared in the form of edematous ridges with prominent furrows and erosion of the dome shaped papillae with rosette shaped deep lesions as a result of which deep parenchymatous tissues were exposed. The collapse of sensory bulbs as well as sloughing of tegument, particularly in the anterior-mid region was observed. The nature of damage could be comparable to various anthelmintics used in previous studies. To the best of our knowledge this is the first report of direct exposure of amphistome worms to zinc metallo-enzyme inhibitor, however, further in vivo studies are required to ascertain the anthelmintic efficacy of 1,10-phe.

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Fasciola hepatica: surface and internal tegumental changes induced by treatment in vitro with the sulphoxide metabolite of albendazole (‘Valbazen’)

Parasitology ◽

10.1017/s0031182002002664 ◽

2003 ◽

Vol 126 (2) ◽

pp. 141-153 ◽

Cited By ~ 43

Author(s):

J. F. BUCHANAN ◽

I. FAIRWEATHER ◽

G. P. BRENNAN ◽

A. TRUDGETT ◽

E. M. HOEY

Keyword(s):

Electron Microscopy ◽

Fasciola Hepatica ◽

Benzimidazole Derivative ◽

Microtubule Inhibitors ◽

Transmission Electron ◽

Basal Plasma ◽

Benzimidazole Anthelmintic ◽

Distinct Increase ◽

Surface Changes

A morphological study has been carried out to determine the effect of the active sulphoxide metabolite of the benzimidazole anthelmintic, albendazole (ABZ-SO) on the adult liver fluke, Fasciola hepatica. Whole flukes were treated with ABZ-SO for 12 and 24 h at a concentration of 10 μg/ml. The changes in response to drug treatment were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and tubulin immunocytochemistry (ICC). No surface changes were apparent following 12 h ABZ-SO treatment, but localized blebbing was observed after 24 h, which became more extensive towards the posterior region of both surfaces. TEM of sections from the posterior midbody region revealed that ABZ-SO caused the accumulation of secretory bodies in the tegumental cells and in their cytoplasmic connections and, after 24 h, just above the basal plasma membrane. Localized blebbing of the apical membrane also occurred. The morphology of the Golgi complexes within the tegumental cells began to change after 12 h treatment with ABZ-SO and, by 24 h, few complexes were observed. A distinct increase in tubulin immunoreactivity occurred after 12 h treatment, but this decreased after 24 h. The results obtained are consistent with those expected for microtubule inhibition. They are discussed in relation to the action of established microtubule inhibitors, as well as the benzimidazole derivative, triclabendazole.

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Fasciola hepatica : tegumental surface alterations following treatment in vivo and in vitro with nitroxynil (Trodax)

Parasitology Research ◽

10.1007/s00436-003-0930-6 ◽

2003 ◽

Vol 91 (3) ◽

pp. 251-263 ◽

Cited By ~ 48

Author(s):

B. McKinstry ◽

I. Fairweather ◽

G. P. Brennan ◽

A. B. Forbes

Keyword(s):

Fasciola Hepatica ◽

Tegumental Surface

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Tegumental surface changes in adult Paramphistomum microbothrium (Fischoeder 1901) following in vitro administration of artemether

Journal of Helminthology ◽

10.1017/s0022149x09990356 ◽

2009 ◽

Vol 84 (2) ◽

pp. 115-122 ◽

Cited By ~ 11

Author(s):

H.A. Shalaby ◽

A.H. El Namaky ◽

R.A. Kamel ◽

A.A. Derbala

Keyword(s):

Oral Sucker ◽

The Body ◽

Neglected Tropical Disease ◽

Oral Aperture ◽

Naked Eye ◽

Tegumental Surface ◽

First Time ◽

Scanning Electron ◽

Surface Changes

AbstractThe treatment of paramphistomiasis, a neglected tropical disease, has been carried out with different fasciolicidal compounds, all showing weak efficacy. Therefore, the search for alternative paramphistomicidal drugs is warranted. In the present study, the in vitro effects of artemether on adult Paramphistomum microbothrium were evaluated, for the first time, using scanning electron microscopy. After 24 h of incubation with 10 μg ml− 1 artemether, tegumental damage of both anterior and posterior ends of the fluke had occurred in the majority of the specimens examined. Sensory papillae surrounding the oral aperture were ruptured, while those at the acetabular region appeared to be sunken due to tegumental swelling. The tegumental disruption became more pronounced and both oral sucker and acetabulum were severely distorted, on increasing the concentration to 20 μg ml− 1. With higher concentration of 30 μg ml− 1, gross swellings of the body of the fluke, clearly visible to the naked eye, were observed, and damage to both oral sucker and acetabulum was so extreme that little recognizable structure remained.

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Fasciola hepatica: tegumental surface alterations following treatment in vitro with the deacetylated (amine) metabolite of diamphenethide

Zeitschrift für Parasitenkunde Parasitology Research ◽

10.1007/bf00536464 ◽

1987 ◽

Vol 73 (2) ◽

pp. 99-106 ◽

Cited By ~ 26

Author(s):

I. Fairweather ◽

H. R. Anderson ◽

T. M. A. Baldwin

Keyword(s):

Fasciola Hepatica ◽

Tegumental Surface

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Tegumental surface changes in adult Fasciola hepatica in response to treatment in vivo with triclabendazole in the sheep host

Veterinary Parasitology ◽

10.1016/j.vetpar.2010.05.012 ◽

2010 ◽

Vol 172 (3-4) ◽

pp. 238-248 ◽

Cited By ~ 19

Author(s):

E. Toner ◽

G.P. Brennan ◽

R.E.B. Hanna ◽

H.W. Edgar ◽

I. Fairweather

Keyword(s):

Fasciola Hepatica ◽

Response To Treatment ◽

Tegumental Surface ◽

Surface Changes

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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 ◽

10.1007/s00436-003-0863-0 ◽

2003 ◽

Vol 91 (3) ◽

pp. 238-250 ◽

Cited By ~ 42

Author(s):

M. Meaney ◽

I. Fairweather ◽

G. P. Brennan ◽

L. S. L. McDowell ◽

A. B. Forbes

Keyword(s):

Fasciola Hepatica ◽

Tegumental Surface

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The soluble glutathione transferase superfamily: role of Mu class in triclabendazole sulphoxide challenge in Fasciola hepatica

Parasitology Research ◽

10.1007/s00436-021-07055-5 ◽

2021 ◽

Vol 120 (3) ◽

pp. 979-991

Author(s):

Rebekah B. Stuart ◽

Suzanne Zwaanswijk ◽

Neil D. MacKintosh ◽

Boontarikaan Witikornkul ◽

Peter M. Brophy ◽

...

Keyword(s):

In Vitro Culture ◽

Liver Fluke ◽

Glutathione Transferase ◽

Fasciola Hepatica ◽

Affinity Purification ◽

Economic Loss ◽

Differential Abundance ◽

Parasitic Helminths

AbstractFasciola hepatica (liver fluke), a significant threat to food security, causes global economic loss for the livestock industry and is re-emerging as a foodborne disease of humans. In the absence of vaccines, treatment control is by anthelmintics; with only triclabendazole (TCBZ) currently effective against all stages of F. hepatica in livestock and humans. There is widespread resistance to TCBZ and its detoxification by flukes might contribute to the mechanism. However, there is limited phase I capacity in adult parasitic helminths with the phase II detoxification system dominated by the soluble glutathione transferase (GST) superfamily. Previous proteomic studies have demonstrated that the levels of Mu class GST from pooled F. hepatica parasites respond under TCBZ-sulphoxide (TCBZ-SO) challenge during in vitro culture ex-host. We have extended this finding by exploiting a sub-proteomic lead strategy to measure the change in the total soluble GST profile (GST-ome) of individual TCBZ-susceptible F. hepatica on TCBZ-SO-exposure in vitro culture. TCBZ-SO exposure demonstrated differential abundance of FhGST-Mu29 and FhGST-Mu26 following affinity purification using both GSH and S-hexyl GSH affinity. Furthermore, a low or weak affinity matrix interacting Mu class GST (FhGST-Mu5) has been identified and recombinantly expressed and represents a new low-affinity Mu class GST. Low-affinity GST isoforms within the GST-ome was not restricted to FhGST-Mu5 with a second likely low-affinity sigma class GST (FhGST-S2) uncovered. This study represents the most complete Fasciola GST-ome generated to date and has supported the potential of subproteomic analyses on individual adult flukes.

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