Key points are not available for this paper at this time.
Abstract Oxidative stress, a major player in secondary brain injury, has been shown to contribute to apoptosis, neuroinflammation, and mitochondrial dysfunction. The possibility of targeting the Nrf2-Keap-ARE pathway, using mitochondria-targeted antioxidants, such as mitoquinone (MitoQ), has been proposed to treat neurotoxicity. The neuroprotective effects of MitoQ on human neuroblastoma SH-SY5Y cells were assessed by MTT assay, SRB assay, and propidium iodide stain using MitoQ at concentrations of 0.03 and 0.05 µg/mL as pre-treatment or post-treatment for hydrogen peroxide (H2O2)-induced stress. Oxidative stress was evaluated by NBT assay and DHE staining while mitochondrial integrity was studied using MitotrackerGreen dye. The gene expression profile of the antioxidant genes Nrf2, SOD1, HOX1, and CAT and the inflammatory genes COX-2 and NFκB were investigated via RT-qPCR along with immunofluorescence imaging. Our results showed that pre-treatment with MitoQ protected SH-SY5Y cells by increasing cell viability, decreasing cell growth inhibition, preserving cell morphology and cell cycle integrity, and attenuating oxidative stress progression while preserving mitochondrial phenotype. The Nrf2-Keap-ARE pathway was demonstrated to be contributing to the protective effects of MitoQ with an upregulation of the antioxidant genes Nrf2 and HMOX1 along with the normalization of SOD1 gene expression. Finally, the decrease in COX-2 levels underscores the anti-inflammatory effect of the antioxidant which supports the use of MitoQ as a treatment for neurotoxicity.
Barsa et al. (Wed,) studied this question.