Bisphenol A Induces Neuronal Apoptosis and Oxidative Stress Through TRPV4 Channel Signaling Pathways: Protective Role of Alpha‐Lipoic Acid

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Bisphenol A (BPA), an environmental toxin, exerts adverse effects by increasing mitochondrial (mROS) and intracellular (iROS) reactive oxygen species, apoptosis, and Ca 2+ influx in neurological diseases. However, antioxidants can mitigate these detrimental effects. This study aimed to investigate the protective role of antioxidant alpha‐lipoic acid (ALA) against BPA‐induced TRPV4 channel stimulation, oxidant, and apoptotic changes in SH‐SY5Y neuronal cells. Five experimental groups were established: control, ALA, BPA, BPA + ALA, and BPA + TRPV4 antagonist (ruthenium red, RuR). BPA increased excessive Ca 2+ influx and TRPV4 current density, while BPA‐ and TRPV4 agonist (GSK1016790A)‐induced TRPV4 stimulations were downregulated following incubation with ALA and RuR. BPA‐induced increases in oxidant markers (lipid peroxidation, mROS, iROS), apoptotic markers (caspase‐3, −8, and −9), Zn 2+ , and cell death were reduced by ALA and RuR treatment. Conversely, BPA‐induced reductions in cell viability, glutathione, and glutathione peroxidase levels were restored following treatment. In summary, ALA attenuated BPA‐induced excess Ca 2+ influx, Zn 2+ accumulation, apoptosis, and oxidative neurotoxicity via TRPV4 inhibition. Therefore, ALA may offer protection against BPA‐induced neuronal cell death associated with oxidative neurotoxicity.