Comparative evaluation of the effects of bisphenol A and/or bisphenol F on oxidative stress and cytokine responses in SH-SY5Y neuroblastoma cells: in silico and in vitro

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical, whereas bisphenol F (BPF), a common BPA substitute, is less characterized, particularly regarding neuronal-derived cells and combined BPA + BPF exposure. Human SH-SY5Y neuroblastoma cells were exposed to BPA, BPF, or BPA + BPF for 24 h. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and oxidative stress and cytokine endpoints were evaluated at IC20 concentrations. SwissTargetPrediction and molecular docking were used to examine potential interactions with estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and androgen receptor (AR). BPA was more cytotoxic than BPF, with IC50 values of 173.2 and 456.8 µM, respectively; the BPA + BPF combination IC50 was 196.9 µM. BPA and BPA + BPF significantly increased reactive oxygen species by 15.74% and 18.32% and protein carbonyl levels by 227.69% and 172.67%, respectively. BPA markedly increased interleukin-6, whereas BPF strongly increased tumor necrosis factor-alpha. In contrast, TNF-α decreased in the BPA and BPA + BPF groups, while malondialdehyde showed a non-significant downward trend. Docking predicted interactions of both compounds with AR, ERα, and ERβ, with binding energies of −7.3 to −8.5 kcal/mol. BPA and BPF produced distinct cytotoxic, oxidative, and cytokine-response profiles after acute exposure. BPA-containing treatments were associated with greater oxidative stress-related changes, whereas BPF elicited a distinct inflammatory response. Predicted receptor interactions require functional validation, and further studies should assess chronic, low-dose, and mixed exposures.