Suberoylanilide Hydroxamic Acid (SAHA) Reduces Glutamate-Induced Oxidative Stress in Hippocampal Cells

Glutamate is an essential excitatory neurotransmitter in the brain, neuronal cell loss by overactivation in high concentrations. Epigenetic mechanisms, such as histone modifications, alter gene expression for maintaining cellular balance and are activated during sustained neuroinflammation and oxidative stress. Suberoylanilide hydroxamic acid (SAHA) is a well-known histone deacetylase inhibitor for its antitumor and anti-inflammatory properties. Therefore, in this study, we aimed to investigate the neuroprotective effect of SAHA against glutamate-induced oxidative stress in HT-22 hippocampal cells. Materials and Methods: The HT-22 hippocampal neuronal cells were cultured in DMEM medium with 10% FBS and 1% penicillin/streptomycin and incubated at 37°C in a humidified atmosphere containing 5% CO 2 . Cell viability was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay after administration of glutamate and SAHA to HT-22 cells, and then the absorbance levels were measured at 550 nm using a microplate reader. The neuroprotective effect of SAHA was evaluated by measuring the oxidative stress parameters like reduced glutathione (GSH) level, and antioxidant enzyme activities of glutathione reductase (GR) and glutathione peroxide (GPx) by Enzyme-like immunosorbent assay (ELISA). Results: SAHA has reduced glutamate-induced neuron death in HT-22 cells. Moreover, SAHA alleviated glutamate-induced oxidative stress by increasing GSH levels, and the activities of the antioxidant enzymes GR and GPx. Conclusion: These results demonstrated that SAHA has antioxidant activity, reduces glutamate-induced oxidative stress, and confers protection against glutamate-induced neuronal death.