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Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins

Mudyanselage, Anusha W.; Wijamunige, Buddhika C.; Kocon, Artur; Carter, Wayne G.

Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins Thumbnail


Authors

Anusha W. Mudyanselage

Buddhika C. Wijamunige

Artur Kocon



Contributors

James O’Callaghan
Editor

Abstract

Organophosphate (OP) and carbamate pesticides are toxic to pests through targeted inhibition of acetylcholinesterase (AChE). However, OPs and carbamates may be harmful to non-target species including humans and could induce developmental neurotoxicity if differentiated or differentiating neurons are particularly vulnerable to neurotoxicant exposures. Hence, this study compared the neurotoxicity of OPs, chlorpyrifos-oxon (CPO), and azamethiphos (AZO) and the carbamate pesticide, aldicarb, to undifferentiated versus differentiated SH-SY5Y neuroblastoma cells. OP and carbamate concentration-response curves for cell viability were undertaken using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and cellular bioenergetic capacity assessed via quantitation of cellular ATP levels. Concentration-response curves for inhibition of cellular AChE activity were also generated and the production of reactive oxygen species (ROS) was monitored using a 2′,7′-dichlorofluorescein diacetate (DCFDA) assay. The OPs and aldicarb reduced cell viability, cellular ATP levels, and neurite outgrowth in a concentration-dependent fashion, from a threshold concentration of ≥10 µM. Neurotoxic potency was in the order AZO > CPO > aldicarb for undifferentiated cells but CPO > AZO > aldicarb for differentiated cells and this toxic potency of CPO reflected its more extensive induction of reactive oxygen species (ROS) and generation of carbonylated proteins that were characterized by western blotting. Hence, the relative neurotoxicity of the OPs and aldicarb in part reflects non-cholinergic mechanisms that are likely to contribute to developmental neurotoxicity.

Journal Article Type Article
Acceptance Date Apr 25, 2023
Online Publication Date Apr 26, 2023
Publication Date May 1, 2023
Deposit Date Apr 29, 2023
Publicly Available Date May 3, 2023
Journal Brain Sciences
Electronic ISSN 2076-3425
Publisher MDPI AG
Peer Reviewed Peer Reviewed
Volume 13
Issue 5
Article Number 728
DOI https://doi.org/10.3390/brainsci13050728
Keywords aldicarb; azamethiphos; chlorpyrifos; cholinergic toxicity; developmental neurotoxicity; non-cholinergic mechanisms; pesticides
Public URL https://nottingham-repository.worktribe.com/output/20008745
Publisher URL https://www.mdpi.com/2076-3425/13/5/728

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Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins (4.7 Mb)
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/

Copyright Statement
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).





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