Abstract
Objective: The aim of this study was to explain the benefits and possible protective mechanisms of sinapic acid (SA) against cisplatin-induced oxido-inflammatory damage in HT-22 rat hippocampal cells by biochemical and molecular methods. Materials and methods: Sinapic acid (SA) was applied at different concentrations (100, 400, and 800 μM) before cisplatin treatment on HT-22 cells under in vitro conditions to elicit neuroprotective activity. Half an hour after SA treatment, 5.5 μM cisplatin was added to all wells except the control group and incubated for 24 hours. Cell viability was determined by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cytotoxicity was determined by lactate dehydrogenase (LDH) assays. Oxidative stress was evaluated by total antioxidant capacity (TAC), catalase (CAT), glutathione reductase (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) assays. In addition, the effect of SA on Caspase-3 gene regulation in HT-22 cells was investigated by real-time PCR. Results: Cisplatin decreased cell viability by approximately 40% and increased LDH level in HT-22 cells. In SA-treated groups, cell viability increased and LDH level decreased dose-independently. SA showed neuroprotective activity by inhibiting the cytotoxic activity of cisplatin and increasing the antioxidant activity in cells. Similarly, Caspase-3, which was up-regulated by cisplatin, approached the control value upon SA administration. SA eliminated the neurotoxicity of cisplatin and significantly reduced cell death and oxidative stress. Conclusion: The results of this study indicate that SA protects HT-22 cells against cisplatin by inhibiting both the formation of oxidative stress and induction of cell apoptosis.
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