Sesamol prevents mitochondrial impairment and pro-inflammatory alterations in the human neuroblastoma SH-SY5Y cells: role for Nrf2

Mitochondria are a primary source and a target of reactive oxygen species (ROS). Increased mitochondrial production of ROS is associated with bioenergetics decline, cell death, and inflammation. Here we investigated whether a pretreatment (for 24 h) with sesamol (SES; at 12.5—50 µM) would be efficient in preventing the mitochondrial collapse induced by hydrogen peroxide (H₂O₂, at 300 µM) in the human neuroblastoma SH-SY5Y cell line. We have found that a pretreatment with SES at 25 µM decreased the effects of H₂O₂ on lipid peroxidation, protein carbonylation, and protein nitration in membranes obtained from the mitochondria isolated from the SH-SY5Y cells. In this regard, SES pretreatment decreased the production of superoxide anion radical (O₂^−•) by the mitochondria of H₂O₂-treated cells. SES also prevented the mitochondrial dysfunction induced by H₂O₂, as assessed by analyzing the activity of the complexes I and V. The H₂O₂-induced reduction in the production of adenosine triphosphate (ATP) was also prevented by SES. The levels of the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well as the activity of the transcription factor nuclear factor-κB (NF-κB) were downregulated by the SES pretreatment in the H₂O₂-challenged cells. Silencing of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor abolished the protection induced by SES regarding mitochondrial function and inflammation. Thus, SES depends on Nrf2 to promote mitochondrial protection in cells facing redox impairment.