Tegumental surface changes in adult Fasciola hepatica following treatment in vitro and in vivo with an experimental fasciolicide

2004 ◽  
Vol 93 (4) ◽  
Author(s):  
Norma Rivera ◽  
Froyl�n Ibarra ◽  
Armando Zepeda ◽  
Teresa Fortoul ◽  
Alicia Hern�ndez ◽  
...  
2008 ◽  
Vol 155 (1-2) ◽  
pp. 49-58 ◽  
Author(s):  
L. Halferty ◽  
G.P. Brennan ◽  
R.E.B. Hanna ◽  
H.W. Edgar ◽  
M.M. Meaney ◽  
...  

Author(s):  
S.M.A. Abidi ◽  
Kavita Singh ◽  
A. Rehman ◽  
R. Ullah ◽  
L. Rehman ◽  
...  

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.


2003 ◽  
Vol 91 (3) ◽  
pp. 251-263 ◽  
Author(s):  
B. McKinstry ◽  
I. Fairweather ◽  
G. P. Brennan ◽  
A. B. Forbes

2010 ◽  
Vol 172 (3-4) ◽  
pp. 238-248 ◽  
Author(s):  
E. Toner ◽  
G.P. Brennan ◽  
R.E.B. Hanna ◽  
H.W. Edgar ◽  
I. Fairweather

2003 ◽  
Vol 91 (3) ◽  
pp. 238-250 ◽  
Author(s):  
M. Meaney ◽  
I. Fairweather ◽  
G. P. Brennan ◽  
L. S. L. McDowell ◽  
A. B. Forbes

2022 ◽  
Author(s):  
Emily Robb ◽  
Erin McCammick ◽  
Duncan Wells ◽  
Paul McVeigh ◽  
Erica Gardiner ◽  
...  

Fasciola spp. liver fluke have significant impacts in veterinary and human medicine. The absence of a vaccine and increasing anthelmintic resistance threaten sustainable control and underscore the need for novel flukicides. Functional genomic approaches underpinned by in vitro culture of juvenile Fasciola hepatica facilitate control target validation in the most pathogenic life stage. Comparative transcriptomics of in vitro and in vivo maintained 21 day old F. hepatica finds that 86% of genes are expressed at similar levels across maintenance treatments suggesting commonality in core biological functioning within these juveniles. Phenotypic comparisons revealed higher cell proliferation and growth rates in the in vivo juveniles compared to their in vitro counterparts. These phenotypic differences were consistent with the upregulation of neoblast-like stem cell and cell-cycle associated genes in in vivo maintained worms. The more rapid growth/development of in vivo juveniles was further evidenced by a switch in cathepsin protease expression profiles, dominated by cathepsin B in in vitro juveniles and then by cathepsin L in in vivo juveniles. Coincident with more rapid growth/development was the marked downregulation of both classical and peptidergic neuronal signalling components in in vivo maintained juveniles, supporting a role for the nervous system in regulating liver fluke growth and development. Differences in the miRNA complements of in vivo and in vitro juveniles identified 31 differentially expressed miRNAs, notably fhe-let-7a-5p , fhe-mir-124-3p and, miRNAs predicted to target Wnt-signalling, supporting a key role for miRNAs in driving the growth/developmental differences in the in vitro and in vivo maintained juvenile liver fluke. Widespread differences in the expression of neuronal genes in juvenile fluke grown in vitro and in vivo expose significant interplay between neuronal signalling and the rate of growth/development, encouraging consideration of neuronal targets in efforts to dysregulate growth/development for parasite control.


2003 ◽  
Vol 18 ◽  
pp. 48-54 ◽  
Author(s):  
Claude B Rieker ◽  
Reto Konrad ◽  
Rolf Schön ◽  
Werner Schneider ◽  
Niels A Abt
Keyword(s):  

Parasitology ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 589-603 ◽  
Author(s):  
J. KEISER

SUMMARYSchistosomiasis and food-borne trematodiases are chronic parasitic diseases affecting millions of people mostly in the developing world. Additional drugs should be developed as only few drugs are available for treatment and drug resistance might emerge. In vitro and in vivo whole parasite screens represent essential components of the trematodicidal drug discovery cascade. This review describes the current state-of-the-art of in vitro and in vivo screening systems of the blood fluke Schistosoma mansoni, the liver fluke Fasciola hepatica and the intestinal fluke Echinostoma caproni. Examples of in vitro and in vivo evaluation of compounds for activity are presented. To boost the discovery pipeline for these diseases there is a need to develop validated, robust high-throughput in vitro systems with simple readouts.


Parasitology ◽  
2003 ◽  
Vol 126 (2) ◽  
pp. 141-153 ◽  
Author(s):  
J. F. BUCHANAN ◽  
I. FAIRWEATHER ◽  
G. P. BRENNAN ◽  
A. TRUDGETT ◽  
E. M. HOEY

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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