Cerium Oxide Nanoparticles Rescue Dopaminergic Neurons in Parkinson’s Disease Model of SH-SY5Y Cells via Modulating Nrf2 Signaling and Ameliorating Apoptotic Cell Death

Objective: This study was designed to explore the potential neuroprotective role of cerium oxide nanoparticles, which are known to have antioxidant properties, in 6-hyd roxyd opami ne-in duced Parkinson’s disease in SH-SY5Y cells. Methods: SH-SY5Y cells were exposed to 200 μM 6-hydroxydopamine for 24 hours to mimic Parkinson’s disease model in vitro. Cells were treated with cerium oxide nanoparticles (25, 50, and 100 μg/mL) for 30 minutes before 6-hydroxydopamine administration. Cell viability was determined by (3-[4 ,5-di methy lthia zol-2 -yl]- 2,5-d iphen yl tetrazolium bromide) and lactate dehydrogenase assays. The neuroprotective effect of cerium oxide nanoparticles on 6-hyd roxyd opami ne-re lated oxidative damage was assessed with malondialdehyde, superoxide dismutase, and catalase analyses. The effects of cerium oxide nanoparticles on NRF2 expression in 6-hyd roxyd opami ne-as socia ted neurotoxicity were evaluated by the reverse transcriptase polymerase chain reaction. Moreover, BAX and BCL-2 expression levels were analyzed to determine the apoptosis. Results: Cerium oxide nanoparticles at concentrations of 50 and 100 μg/mL showed protective effects against 6-hyd roxyd opami ne-in duced cell damage. Moreover, cerium oxide nanoparticles (at 50 and 100 μg/mL) attenuated oxidative injury evoked by 6-hydroxydopamine as determined by decreased malondialdehyde level probably through the improvement of antioxidant capacity by elevating superoxide dismutase and catalase. Cerium oxide nanoparticles promoted the NRF2 transcriptional activity. Finally, we found that this nanoparticle (at 50 and 100 μg/mL) reversed the 6-hyd roxyd opami ne-re lated elevation of BAX levels and reduction of BCL-2 level. Conclusion: Collectively, cerium oxide nanoparticles prevented 6-hyd roxyd opami ne-in duced toxicity in SH-SY5Y cells in a dosedependent manner by activating Nrf2 signaling-related antioxidant pathways and alleviating apoptotic neuronal cell death.