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

ÇINAR R., NAZIROĞLU M.

Environmental Toxicology, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/tox.24541
  • Dergi Adı: Environmental Toxicology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, Environment Index, Food Science & Technology Abstracts, Geobase, Greenfile, MEDLINE, Pollution Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: alpha-lipoic acid, apoptosis, bisphenol A, oxidative neurotoxicity, TRPV4 channel
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Evet

Özet

Bisphenol A (BPA), an environmental toxin, exerts adverse effects by increasing mitochondrial (mROS) and intracellular (iROS) reactive oxygen species, apoptosis, and Ca2+ 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 Ca2+ 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), Zn2+, 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 Ca2+ influx, Zn2+ accumulation, apoptosis, and oxidative neurotoxicity via TRPV4 inhibition. Therefore, ALA may offer protection against BPA-induced neuronal cell death associated with oxidative neurotoxicity.