Does Sinapic Acid Provide Neuroprotection Against Cisplatin-Induced Toxicity in HT-22 Cells

INTRODUCTION: This study aimed to explain the beneficial effects 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. METHODS: Primarily, different concentrations of SA (100, 400 and 800 µM) were applied to HT-22 cells under in vitro conditions before cisplatin application in order to produce neuroprotective activity. Half an hour after the SA application, 5.5 µM cisplatin (CP) was applied to all wells except the control group and incubated for 24 hours under appropriate conditions. Cell viability was determined with routinely used 3-(4,5-Dimethyl Thiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and cytotoxic activity was determined by lactate dehydrogenase (LDH) assays. Oxidative stress was evaluated by total antioxidant capacity (TAC), catalase (CAT), glutathione (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 administered groups, cell viability increased and LDH level decreased regardless of dose. SA showed its neuroprotective effect by stopping the cytotoxic activity of cisplatin and increasing its antioxidant action mechanism in cells. Similarly, caspase-3 up-regulated by cisplatin approached the control value with SA administration. SA abolished the neurotoxicity of cisplatin and significantly reduced cell death and oxidative stress levels (p<0.05 and p<0.001). DISCUSSION AND CONCLUSION: These findings show that SA protects HT-22 cells against cisplatin by preventing both oxidative stress formation mechanisms and apoptosis induction of cells.