The neurotoxicity of
fluoride is associated with oxidative stress due to imbalance between production and removal of
reactive oxygen species (ROS). In contrast, induction of detoxifying and
antioxidant genes through activation of
NF-E2-related factor 2 (Nrf2) has been implicated in preventing oxidative stress and apoptosis in
neurodegenerative diseases. The present study aimed to investigate the possible neuroprotective role of
tert-butylhydroquinone (
tBHQ), a general Nrf2 activator, on
sodium fluoride (NaF)-induced oxidation damage and apoptosis in neuron-like rat
pheochromocytoma (PC12) cells. Pretreatment with
tBHQ protected PC12 cells against NaF-induced cytotoxicity as measured by MTT assay and apoptosis detection, simultaneously, inhibited NaF-induced overproduction of intracellular ROS and reduction of total
glutathione content. Furthermore, NaF or
tBHQ induced the stabilization of Nrf2, and enhanced expression of
heme oxygenase-1 (HO-1) and γ-
glutamylcysteine synthetase (γ-GCS) as a consequence of Nrf2 inducing. These findings indicated that
tBHQ pretreatment conferred protective effect on PC12 cells against NaF-induced apoptotic cell death and oxidation-redox imbalance through stabilization of Nrf2 and elevation of downstream HO-1 and γ-GCS expressions.