Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 08 2020
10 08 2020
Historique:
received:
30
04
2020
accepted:
21
07
2020
entrez:
12
8
2020
pubmed:
12
8
2020
medline:
18
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32778698
doi: 10.1038/s41598-020-69970-4
pii: 10.1038/s41598-020-69970-4
pmc: PMC7418001
doi:
Substances chimiques
Anthelmintics
0
Triclabendazole
4784C8E03O
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
13445Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S00324X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S00324X/1
Pays : United Kingdom
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