Naringenin Attenuates HO-Induced Mitochondrial Dysfunction by an Nrf2-Dependent Mechanism in SH-SY5Y Cells.

Mitochondria are the major site of ATP production in mammalian cells. Furthermore, these organelles are a source and a target of reactive oxygen species (ROS), such as radical anion superoxide (O) and hydrogen peroxide (HO). The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is the master regulator of the mammalian redox biology and controls the expression of antioxidant and phase II detoxifying enzymes in several cell types. Naringenin (NGN, 5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one), a flavanone, exhibits cytoprotective effects by acting as an antioxidant and anti-inflammatory agent. NGN is a potent activator of Nrf2. Nonetheless, it was not examine yet whether NGN would induce mitochondrial protection in cells under redox stress. Therefore, we investigate here whether Nrf2 would be involved in the mitochondrial protection elicited by NGN in SH-SY5Y cells exposed to HO. We observed that a pretreatment with NGN at 80 µM for 2 h reduced the levels of lipid peroxidation, protein carbonylation, and protein nitration in the membranes of mitochondria obtained from HO-treated SH-SY5Y cells. Additionally, NGN prevented the HO-induced impairment in the function of the enzymes aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. The activites of the complexes I and V, as well as the production of ATP, were restored by NGN. NGN also suppressed the HO-induced mitochondria-related apoptosis. Interestingly, NGN promoted an increase in the levels of both total and mitochondrial glutathione (GSH). Silencing of Nrf2 abolished the protective effects induced by NGN. Overall, NGN induced mitochondrial protection by an Nrf2-dependent mechanism in HO-treated SH-SY5Y cells.