Examining the developmental toxicity of piperonyl butoxide as a Sonic hedgehog pathway inhibitor.

Autor: Rivera-González KS; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA; Molecular and Environmental Toxicology Graduate Training Program, University of Wisconsin-Madison, Madison, WI, 53706, USA., Beames TG; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA; Molecular and Environmental Toxicology Graduate Training Program, University of Wisconsin-Madison, Madison, WI, 53706, USA., Lipinski RJ; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53706, USA; Molecular and Environmental Toxicology Graduate Training Program, University of Wisconsin-Madison, Madison, WI, 53706, USA. Electronic address: robert.lipinski@wisc.edu.
Jazyk: angličtina
Zdroj: Chemosphere [Chemosphere] 2021 Feb; Vol. 264 (Pt 1), pp. 128414. Date of Electronic Publication: 2020 Sep 23.
DOI: 10.1016/j.chemosphere.2020.128414
Abstrakt: Piperonyl butoxide (PBO) is a semisynthetic chemical present in hundreds of pesticide formulations used in agricultural, commercial, and residential settings. PBO acts as a pesticide synergist by inhibiting insect cytochrome P450 enzymes and is often present at much higher concentrations than active insecticidal ingredients. PBO was recently discovered to also inhibit Sonic hedgehog (Shh) signaling, a key molecular pathway in embryonic development and in brain and face morphogenesis. Recent animal model studies have shown that in utero PBO exposure can cause overt craniofacial malformations or more subtle neurodevelopmental abnormalities. Related adverse developmental outcomes in humans are etiologically heterogeneous, and, while studies are limited, PBO exposure during pregnancy has been linked to neurodevelopmental deficits. Contextualized in PBO's newly recognized mechanism as a Shh signaling inhibitor, these findings support more rigorous examination of the developmental toxicity of PBO and its potential contribution to etiologically complex human birth defects. In this review, we highlight environmental sources of human PBO exposure and summarize existing animal studies examining the developmental impact of prenatal PBO exposure. Also presented are critical knowledge gaps in our understanding of PBO's pharmacokinetics and potential role in gene-environment and environment-environment interactions that should be addressed to better understand the human health impact of environmental PBO exposure.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020. Published by Elsevier Ltd.)
Databáze: MEDLINE
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