Neuroprotective effects of tert-butylhydroquinone on paraquat-induced dopaminergic cell degeneration in C57BL/6 mice and in PC12 cells

Abstract

The present study was aimed at determining the role of paraquat (PQ) in the activation of the NF-E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway and the possible neuroprotective effects of tert-butylhydroquinone (tBHQ) pretreatment on PQ-induced neurodegeneration in vivo and in vitro. 7 mg/kg PQ treatment of male C57BL/6 mice caused decreased spontaneous locomotor activity, decreased tyrosine hydroxylase (TH)-positive neurons, increased terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL)-positive cells in the substantia nigra, as well as increased protein levels of both nuclear Nrf2 and HO-1. In PQ-treated mice, pretreatment with 1 % tBHQ (w/w) significantly attenuated impairments in behavioral performance, decreased TH-positive neurons, and increased TUNEL-positive cells in the substantia nigra, as well as increased protein expression of both nuclear Nrf2 and HO-1. Pretreatment with 40 μM tBHQ protected PC12 cells against 100 and 300 μM PQ-mediated cytotoxicity. The dual-luciferase reporter gene also revealed that the transcriptional activation of HO-1 gene expression of the antioxidant responsive element via Nrf2 occurred as a consequence of 100 and 300 μM PQ exposure. Collectively, these results clearly indicated for the first time that the Nrf2/HO-1 pathway in the substantia nigra was activated by PQ, and pretreatment with tBHQ conferred neuroprotection against PQ-induced Parkinsonism presumably by increasing Nrf2 and HO-1 expression.

Neuroprotective Effect of Didymin on Hydrogen Peroxide-Induced Injury in the Neuronal Membrane System

“…In order to have an in vitro model of oxidative stress, neuronal cells after 7 days of culture in the PCL membrane system were initially subjected to H 2 O 2 treatment before the administration of didymin for the next 24 h. In spite of the high percentage of cell death, administration of didymin significantly attenuated cell death and reduced the intracellular ROS levels. As a positive control we used tBHQ since it is known as a strong inducer of phase II detoxification enzymes which have antioxidative functions [Hara et al, 2003;Li et al, 2012]. Lee et al [2001] demonstrated that the treatment with tBHQ prevented H 2 O 2 -induced apoptosis and induced many genes associated with resistance against oxidative stress in neuronal cells.…”

Sequential Upregulation of Superoxide Dismutase 2 and Heme Oxygenase 1 by tert-Butylhydroquinone Protects Mitochondria during Oxidative Stress

“…ARE-driven genes are involved in production of a battery of antioxidant and phase 2 enzymes, which is a potent strategy to repress oxidative damage (Calkins et al, 2009). Among Nrf2-regulated phase 2 enzymes, heme oxygenase 1 (HO-1), the rate-limiting enzyme in catalysis of heme, has been reported to be critical for the protective effect of the Nrf2-ARE signaling pathway in neurodegenerative diseases (Satoh et al, 2006;Li et al, 2012;Alfieri et al, 2013).…”

Neuroprotective activities of fermented Ganoderma lucidum extracts by lactic acid bacteria against H2O2-stimulated oxidative stress in PC12 cells

“…Neurodegenerative diseases refer to cerebral or spinal disorders caused by abnormal neuronal death and are accompanied by impaired cognitive, walking, and motor abilities (2). As oxygen free radicals are known to be largely responsible for these degenerative diseases, more research and development into technologies to control oxygen free radicals are being conducted (3)(4)(5). Oxidative stress induces lipid peroxidation, injury to protein, cell membranes, and DNA, and cell aging and deformation, resulting in various neurodegenerative diseases such as stroke, Alzheimer's disease, and Parkinson's disease (6,7).…”