Organophosphate (OP) and carbamate compounds are widely employed pesticides that are toxic to target species through targeted inhibition of acetylcholinesterase (AChE). However, their toxicity to off-target species including humans remains a health and environmental concern. The neurotoxicity of a 24-hour exposure to the OP pesticides chlorpyrifos-oxon (CPO) and azamethiphos-oxon (AZO), and the carbamate pesticide, aldicarb, were investigated using undifferentiated and differentiated SH-SY5Y neuroblastoma cells. Pesticide concentration-response curves for cell viability were undertaken using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assays. Concentration-response curves for pesticide 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. Pesticides reduced cell viability and neurite outgrowth in a concentration-dependent fashion, from a threshold pesticide 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 ROS and generation of carbonylated proteins that were characterized by Western blotting. Hence, the relative neurotoxicity of OP pesticides and aldicarb in part reflects non-cholinergic mechanisms that likely contribute to tissue injury.
Physiology 2023 (Harrogate, UK) (2023) Proc Physiol Soc 54, PCA085
Poster Communications: Differentiated neurons are damaged by organophosphate and carbamate pesticides by non-cholinergic mechanisms
Anusha Wijesekara1, Buddhika Wijamunige1, Artur Kocon1, Wayne Carter1,
1School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Uttoxeter Road Derby United Kingdom,
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Where applicable, experiments conform with Society ethical requirements.