Esmanur CIG, Berrin USTUNDAG, Yunus Emre ARVAS
Neuro-Cell Molecular Research - 2026;3(1):20-26
Neuronal damage, which is responsible for the development and progression of many neurological disorders, is closely linked to cellular-level mechanisms, primarily oxidative stress and apoptosis. Oxidative stress, particularly that resulting from the overproduction of reactive oxygen species (ROS), induces biochemical alterations such as lipid peroxidation, protein oxidation and DNA damage. These biochemical changes disrupt neuronal cell integrity and alter cellular functions. This process leads to the activation of intrinsic apoptotic pathways, mitochondrial dysfunction, and programmed cell death. 4-aminopyridine (4-AP) is a potassium channel blocker widely used to induce oxidative damage resulting from excessive neuronal stimulation and is commonly used in experimental neurotoxicity models. The aim of this study is to investigate the effect of sinapic acid (SPA), a naturally occurring phenolic compound with strong antioxidant properties, on 4-AP-induced neuronal damage in human neuroblastoma cells (SH-SY5Y). In the experimental design, cells were divided into four categories: control, SPA, 4-AP, and SPA + 4-AP. In addition to total antioxidant status (TAS), total oxidant status (TOS), and malondialdehyde (MDA) levels, caspase-3 activity-a hallmark marker of apoptosis, was evaluated. According to our findings, 4-AP application led to a significant decrease in TAS levels but increased TOS, MDA, and caspase-3 levels. This suggests that 4-AP application increases oxidative stress and apoptosis in SH-SY5Y cells. In contrast, SPA pre-treatment significantly increased TAS levels and decreased TOS, MDA, and caspase-3 levels compared to the 4-AP group. In conclusion, SPA was shown to significantly modulate oxidative stress and apoptotic processes, thereby mitigating 4-AP-induced neuronal damage. These findings have strengthened the potential of SPA as a neuroprotective agent in oxidative stress-induced neuronal damage.
