Introduction: Parkinson’s disease (PD) is characterized by progressive dopaminergic neurodegeneration and pathological α-synuclein aggregation. Mitochondrial dysfunction and oxidative stress are central to PD pathogenesis, and mitochondrial complex I inhibitors such as rotenone are widely used to model PD-related neurotoxicity in vitro. Boric acid (BA), a boron-containing compound with reported antioxidant and neuroprotective properties, has not been fully explored in PD-related apoptotic mechanisms. Therefore, this study aimed to investigate the neuroprotective and anti-apoptotic effects of BA in a rotenone-induced in vitro PD model using SH-SY5Y human neuroblastoma cells.
Materials and Methods: SH-SY5Y cells were exposed to 50 µM rotenone to induce PD-like neurotoxicity and co-treated with BA at concentrations ranging from 100 to 800 µM. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis-related molecular changes were evaluated by real-time quantitative polymerase chain reaction and Western blot analyses, focusing on key regulators of mitochondrial apoptosis, including BAX (B-cell lymphoma 2 [BCL-2]-associated X protein), BCL-2, and cleaved caspase-3.
Results: Rotenone treatment significantly reduced cell viability compared to control cells. Co-treatment with 200 µM BA markedly restored cell viability (**p<0.01), indicating a strong neuroprotective effect. Molecular analyses demonstrated that BA treatment significantly decreased the BAX/BCL-2 ratio in rotenone-treated cells (p=0.0295), suggesting an attenuation of mitochondria-mediated apoptotic signaling.
Discussion and Conclusion: These findings demonstrate that BA exerts a significant neuroprotective effect against rotenone-induced cytotoxicity by enhancing cell survival and modulating apoptosis-related pathways. BA may represent a promising candidate for mitigating PD-associated neuronal damage, warranting further mechanistic and in vivo investigations.