NF-E2 related factor 2 activation and heme oxygenase-1 induction by tert-Butylhydroquinone protect against deltamethrin-mediated oxidative stress in PC12 cells

Recent findings suggest that oxidative stress caused by pyrethroid pesticides could be closely involved in the neurotoxicity. tert-Butylhydroquinone (tBHQ) is a known inducer of Nrf2-mediated transcription, and treatment of cells with tBHQ can confer protection against H2O2 and 6-hydroxydopamine (6-OHDA). In this study, we investigated the neuroprotective effect of tBHQ against deltamethrin (DM)-induced oxidative stress using rat PC 12 adrenal pheochromocytoma cells. The pretreatment of PC 12 cells with tBHQ significantly reduced DM-induced generation of reactive oxygen species (ROS) and increased intracellular ionized calcium ([Ca (2+)](i)). We also observed that DM or tBHQ induced the expression of NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), a Nrf2-regulated gene. In addition, the Nrf2 antioxidant responsive element (ARE) pathways activated by tBHQ caused a partial inhibition of the DM-induced Nrf2 and HO-1 expression. Altogether, our data clearly indicate that an activation of Nrf2/ARE pathways in PC12 cells by tBHQ treatment protects cells from DM-induced oxidative stress and regulates DM-mediated adaptive responses in PC12 cells via translocation of Nrf2.