Increasing evidence had proved the critical role of
iron in the pathogenesis of numerous
neurodegenerative diseases because of its capacity to promote the formation of
reactive oxygen species (ROS).
Tert-butylhydroquinone (
tBHQ) was a metabolite of
butylated hydroxyanisole, a widely used food
antioxidant. This study was aimed to investigate the protective effects of
tBHQ on a cellular model of
neurodegenerative disease, which was established in PC12 cells by exposure to
ferrous sulfate (FS), and elucidate the potential protective mechanisms. The results showed that FS exposure increased
lactate dehydrogenase (LDH) release and cell apoptosis in PC12 cells, accompanied by significant increases in the bax/bcl-2 ratio,
cytochrome c release, and
caspase-3 cleavage. It also enhanced the ROS production,
malondialdehyde (MDA) content (lipid peroxidation), γ-H2A.X formation (DNA damage), and promoted
nuclear factor kappa B (NF-κB) activation and expressions of
cyclooxygenase-2 (COX-2),
tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β).
tBHQ pretreatment alleviated FS-induced LDH release, cell apoptosis, oxidative stress and inflammatory response by promoting Nrf2 nuclear translocation and the
protein levels of Nrf2 downstream target genes
heme oxygenase-1 (Hmox-1),
nicotinamide adenine dinucleotide phosphate (
NADPH):
quinone oxidoreductase-1 (Nqo1) and
glutathione peroxidase-1 (Gpx1).
tBHQ alleviated the FS-induced LDH release in control
siRNA-treated PC12 cells, but failed to alleviate FS-induced LDH release in Nrf2
siRNA-treated cells. These findings suggested that pretreatment with
tBHQ protected PC12 cells from FS-induced oxidative and inflammatory injury via the Nrf2/ARE pathway.
tBHQ was promising as a potential therapeutic agent for
neurodegenerative diseases induced by
iron toxicity and should be encouraged for further research.