Sevim_2026_J.Biochem.Mol.Toxicol_40_e70681

Neurodegenerative disorders are characterized by progressive neuronal dysfunction, cholinergic impairment, and disruption of cellular homeostasis. Ionic balance and metabolic stability are increasingly recognized as critical contributors to neuronal resilience under injurious conditions. The present study aimed to evaluate the potential protective effects of selected sodium (Na) and potassium (K) salts in differentiated SH-SY5Y neuronal cells subjected to hydrogen peroxide (H2O2; 100 microM), a widely used model of neuronal injury. Following H2O2 exposure, cells were treated with non-toxic concentrations of the following salts: Sodium citrate tribasic dihydrate (Na3C6H5O7.2H2O), Sodium hydrogen carbonate (NaHCO), Disodium hydrogen phosphate (Na2HPO4), Potassium sodium tartrate tetrahydrate (KNaC4H4O6.4H2O). Salt treatments ameliorated the decline in cell viability and partially reversed changes in total antioxidant status (TAS), total oxidant status (TOS), and acetylcholinesterase (AChE) activity induced by H2O2. To further explore potential mechanistic interactions, molecular docking and molecular dynamics (MD) simulations were conducted on human AChE. The salts were found to interact primarily with peripheral residues surrounding the active-site gorge, suggesting a possible allosteric influence rather than direct engagement with the catalytic triad. Among the tested compounds, disodium hydrogen phosphate (Na2HPO4) exhibited the most stable binding profile over 100 ns MD simulations. Overall, these findings provide preliminary evidence that selected Na- and K-based salts may attenuate neuronal injury and support cellular function under stress conditions. Given their established safety profiles and accessibility, these compounds warrant further investigation as potential adjunctive agents for mitigating processes relevant to neurodegeneration.