Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica


Fascioliasis is a neglected zoonotic disease that infects humans and ruminant species worldwide. In the absence of vaccines, control of fascioliasis is primarily via anthelminthic treatment with triclabendazole (TCBZ). Parasitic flatworms, including Fasciola hepatica, are active secretors of extracellular vesicles (EVs), but research has not been undertaken investigating EV anthelmintic sequestration. Adult F. hepatica were cultured in lethal and sub-lethal doses of TCBZ and its active metabolites, in order to collect EVs and evaluate their morphological characteristics, production and anthelmintic metabolite content. Transmission electron microscopy demonstrated that F. hepatica exposed to TCBZ and its metabolites produced EVs of similar morphology, compared to non-TCBZ exposed controls, even though TCBZ dose and/or TCBZ metabolite led to measurable structural changes in the treated F. hepatica tegument. qNano particle analysis revealed that F. hepatica exposed to TCBZ and its metabolites produced at least five times greater EV concentrations than non-TCBZ controls. A combined mass spectrometry and qNano particle analysis confirmed the presence of TCBZ and the TCBZ–sulphoxide metabolite in anthelmintic exposed EVs, but limited TCBZ sulphone was detectable. This data suggests that EVs released from adult F. hepatica have a biological role in the sequestration of TCBZ and additional toxic xenobiotic metabolites.

Publication DOI: https://doi.org/10.1038/s41598-020-69970-4
Divisions: College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences
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Uncontrolled Keywords: General
Publication ISSN: 2045-2322
Last Modified: 12 Mar 2024 08:14
Date Deposited: 11 Aug 2020 14:07
Full Text Link:
Related URLs: https://www.nat ... 598-020-69970-4 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020-08-10
Accepted Date: 2020-07-21
Authors: Milic, Ivana (ORCID Profile 0000-0001-7531-7561)
Devitt, Andrew (ORCID Profile 0000-0002-4651-6761)
Davis, Chelsea N.
Winters, Ana
Cookson, Alan
Brophy, Peter M.
Morphew, Russell M.



Version: Published Version

License: Creative Commons Attribution

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