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Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica
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Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica
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Journal Article
Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica
2020
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/337
/ 631/45
/ 631/601
/ 631/80
/ 692/308
/ 692/420
/ 692/699
/ Animals
/ Anthelmintics - pharmacology
/ Drug Resistance - drug effects
/ Extracellular Vesicles - metabolism
/ Fasciola hepatica - metabolism
/ Humanities and Social Sciences
/ Science
/ Sheep
/ Sheep Diseases - parasitology
/ Tegument
/ Transmission electron microscopy
/ Triclabendazole - metabolism
/ Triclabendazole - pharmacology
/ Triclabendazole - therapeutic use
/ Zoonoses
