Curcumin protects SH-SY5Y cells against glutamate-induced excitotoxicity by maintaining genomic integrity and antioxidant balance

Glutamate-induced excitotoxicity, characterized by oxidative stress and genomic instability, is a hallmark of neurodegenerative disorders. This study investigated the protective effects of curcumin against glutamate-induced excitotoxicity in SH-SY5Y cells, focusing on oxidative balance and DNA integrity. SH-SY5Y cells were exposed to 40 mM L-glutamate to induce excitotoxicity. Cells were concurrently treated with curcumin (2.5-15 µM). Cell viability was assessed via XTT assay. Oxidative status was evaluated by measuring Total Antioxidant Status (TAS) and Total Oxidant Status (TOS). Genomic integrity was analyzed using the Comet assay (Tail DNA%). Exposure to 40 mM glutamate caused ∼50% cell death, significantly increased TOS levels, and induced extensive DNA damage (increased Tail DNA%). Co-treatment with 10 and 15 µM curcumin significantly restored cell viability in a dose-dependent manner. Notably, 10 µM curcumin ameliorated glutamate-induced TAS depletion and significantly reduced DNA fragmentation, restoring genomic stability to near-baseline levels. Curcumin alone exhibited no pro-oxidant or genotoxic effects. Curcumin exerts a significant cytoprotective effect against glutamate excitotoxicity in SH-SY5Y cells. This protection is primarily mediated through the restoration of the cellular antioxidant pool and the preservation of genomic integrity, suggesting curcumin as a promising therapeutic agent for mitigating excitotoxic neuronal damage.