Redox Imbalance, Oxidative DNA Damage, and Mitochondrial Membrane Depolarization Induced by Pervari Honey in SH-SY5Y...

Neuroblastoma remains a challenging malignancy in which redox imbalance and mitochondrial dysfunction represent potential cellular vulnerabilities. This study investigated the redox-associated cytotoxic effects and mitochondrial responses of Pervari honey (PH), a region-specific natural product from Türkiye, in SH-SY5Y neuroblastoma cells. MTT-based viability was assessed in SH-SY5Y neuroblastoma cells and L929 fibroblasts, used as a non-cancerous control cell model, after 48 h of PH exposure. Redox status was evaluated by measuring intracellular reactive oxygen species (ROS), total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Mitochondrial membrane potential (ΔΨm) was analyzed using the JC-10 assay. Expression levels of apoptosis- and antioxidant-related genes were determined by RT-qPCR. Comparative viability analysis showed that L929 fibroblasts were less affected by PH exposure than SH-SY5Y cells, and the IC50 value of PH was not reached in L929 cells within the tested concentration range. Treatment increased ROS production and shifted the oxidant/antioxidant balance toward oxidative stress, as indicated by increased TOS and OSI and decreased TAC and GSH levels. Elevated MDA and 8-OHdG levels confirmed oxidative damage to lipids and DNA. Additionally, PH reduced mitochondrial membrane potential and altered the expression of apoptosis- and antioxidant-related genes, including cytochrome c (Cyt-c), p53, SOD1, and CAT. PH exerted cytotoxic effects in SH-SY5Y cells through redox imbalance and mitochondrial dysfunction. These findings suggest that PH may influence redox-sensitive pathways in neuroblastoma cells. However, further studies including compositional analysis and appropriate controls are required to clarify the underlying mechanisms.