High-fidelity nonanimal screening methods are needed that can rapidly and accurately characterize
organophosphorus compound (OP)-induced neurotoxicity. Herein, the efficacy of human
neuroblastoma cell line (SH-SY5Y) to provide molecular and cellular responses characteristic of the OP neurotoxicity pathway was investigated in response to the OP-model compound,
ethyl-parathion. Undifferentiated SH-SY5Y cells were exposed to
ethyl-parathion for 30 min at 0 (control), 0.5, 2.5, 5, 10, and 25 µg/ml. Dose-responsive reductions in cell viability were observed with significant reductions at ≥10 µg/ml. From these results,
ethyl-parathion exposures of 0 (control), 5, and 10 µg/ml were selected to examine
bioindicators underlying the OP neurotoxicity pathway including:
reactive oxygen species (ROS), cell membrane peroxidation, mitochondrial membrane potential (
MMP), and apoptosis.
Ethyl-parathion elicited highly significant increases in ROS relative to controls (p < .01) at both exposure concentrations, confirmed using N-acetyl
cysteine (NAC) as a ROS quencher which alleviated ROS increases. A response characteristic of increased ROS exposure,
cell membrane-lipid peroxidation, significantly increased (p < .05) at the highest
ethyl-parathion exposure (10 µg/ml). As a likely consequence of
membrane-lipid peroxidation,
ethyl-parathion-induced reductions in
MMP were observed with significant effects at 10 µg/ml, reducing
MMP by 58.2%. As a culmination of these cellular-damage indicators, apoptosis progression was investigated by
phosphatidylserine translocation where
ethyl-parathion-induced dose-responsive, highly significant (p < .01) increases at both 5 and 10 µg/ml. Overall, the mechanistic responses observed in undifferentiated SH-SY5Y cells corresponded with in vivo mammalian results demonstrating potential for this nonanimal model to provide accurate OP neurotoxicology screening.