Tert-butylhydroquinone protects PC12 cells against ferrous sulfate-induced oxidative and inflammatory injury via the Nrf2/ARE pathway

Wenzhe Xu, Feng Li, Zhenkuan Xu, Bin Sun, Jingwei Cao, Yuguang Liu, Chemico-Biological Interactions, Available online 2 June 2017, ISSN 0009-2797, doi:10.1016/j.cbi.2017.05.021

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. tBHQ could change the conformation of the Keap1-Nrf2 complex and helps Nrf2 escape from Keap1-mediated degradation, which can lead to Nrf2 stabilization. tBHQ has been proven to exert neuroprotective effects in different models of CNS injury and has been approved for human use

Free iron exhibits cytotoxicity because of its ability to promote the generation of reactive oxygen species (ROS), which could lead to lipid peroxidation, DNA strand breaks, degradation of biomolecules, and induce inflammatory response. Brain iron content tends to increase during healthy aging, while excessive iron deposits are found in neuritic plaques in brains with Alzheimer’s disease, substantia nigra in Parkinson’s disease, basal ganglia in Huntington’s disease and dorsal root ganglia in Friedreich’s ataxia (FRDA). This study proved the beneficial effects of tBHQ on the attenuation of iron-induced neurotoxicity, suggesting the therapeutic potential of tBHQ for neurodegenerative diseases.