Abstract
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.