Niclosamide Induces Epiboly Delay During Early Zebrafish Embryogenesis

Toxicological Sciences : an Official Journal of the Society of Toxicology
Sara M F VlietDavid C Volz

Abstract

Niclosamide is an antihelminthic drug used worldwide for the treatment of tapeworm infections. Recent drug repurposing screens have revealed that niclosamide exhibits diverse mechanisms of action and, as a result, demonstrates promise for a number of applications, including the treatment of cancer, bacterial infections, and Zika virus. As new applications of niclosamide will require non-oral delivery routes that may lead to exposure in utero, the objective of this study was to investigate the mechanism of niclosamide toxicity during early stages of embryonic development. Using zebrafish as a model, we found that niclosamide induced a concentration-dependent delay in epiboly progression during late-blastula and early-gastrula, an effect that was dependent on exposure during the maternal-to-zygotic transition-a period characterized by degradation of maternally derived transcripts, zygotic genome activation, and initiation of cell motility. Moreover, we found that niclosamide did not affect embryonic oxygen consumption, suggesting that oxidative phosphorylation-a well-established target for niclosamide within intestinal parasites-may not play a role in niclosamide-induced epiboly delay. However, mRNA-sequencing revealed that niclo...Continue Reading

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Citations

Feb 20, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Linlin ZhaoHao Zhu
May 4, 2020·Environmental Toxicology and Chemistry·Jennifer C BrennanDonald E Tillitt

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