Assistant Professor Taipei Medical University Taipei, Taipei, Taiwan (Republic of China)
Abstract: Sodium chlorate (NaClO₃), a strong oxidizing agent widely used in industrial and agricultural applications, poses potential risks to both human health and the environment. This study aimed to investigate the dose-dependent neurotoxic effects of NaClO₃ using human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) and zebrafish as models, with a focus on understanding implications for environmental pollution. We treated iPSC-derived DAn and zebrafish with 10, 30, and 50 mM concentrations of NaClO₃, observing significant effects only at the highest concentration (50 mM). In DAn, 50 mM NaClO₃ treatment led to a marked increase in apoptosis, accompanied by upregulation of cell cycle regulators P16 and P21, indicating stress-induced senescence and apoptosis specifically in iPSC-derived neurons. Additionally, zebrafish treated with 50 mM NaClO₃ exhibited notable reductions in movement distance and speed, suggesting impaired motor function. qPCR analysis revealed that NaClO₃ at this concentration significantly downregulated tyrosine hydroxylase (TH) expression in zebrafish and upregulated genes associated with oxidative stress (CAT, GPX1, SOD1/2) and apoptosis (Bcl2b, Caspase 3b, Caspase 8, Caspase 9) in the brain. These findings indicate that NaClO₃ exhibits significant neurotoxicity at higher concentrations, particularly affecting iPSC-derived dopaminergic neurons and motor behavior through oxidative stress and apoptosis pathways. Given these neurotoxic effects, high concentrations of NaClO₃ in industrial waste and agricultural runoff may pose serious risks to aquatic ecosystems and organisms, highlighting the importance of regulating NaClO₃ emissions to prevent environmental and ecological harm.
Funding Source: This work was supported by the National Science and Technology Council [grant numbers: NSTC 112-2314-B-038-043]
