Anusha W. Mudyanselage
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.
Authors
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.
Citation
Mudyanselage, A. W., Wijamunige, B. C., Kocon, A., & Carter, W. G. (2023). 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. Brain Sciences, 13(5), Article 728. https://doi.org/10.3390/brainsci13050728
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 |
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
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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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