Neuroprotective effects of tert-butylhydroquinone on paraquat-induced dopaminergic cell degeneration

Huangyuan LI; Siying WU; Zhangjing WANG; Wei LIN; Chenzi ZHANG; Bin HUANG

doi:10.14869/toxpt.39.2.0.AP-92.0

The 6th International Congress of Asian Society of Toxicology

Session ID : AP-92

DOI https://doi.org/10.14869/toxpt.39.2.0.AP-92.0

Conference information

Host: The Japanese Society of Toxicology

Agricultural chemical & Food additive

Neuroprotective effects of tert-butylhydroquinone on paraquat-induced dopaminergic cell degeneration

*Huangyuan LI, Siying WU, Zhangjing WANG, Wei LIN, Chenzi ZHANG, Bin HUANG

Author information

*Huangyuan LI
Department of Occupational and Environmental Health, Fujian Province Key lab of Environment and Health, Institution of Environment and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, China
Siying WU
Department of Epidemiology and Health Statistics, Fujian Province Key lab of Environment and Health, Institution of Environment and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, China
Zhangjing WANG
Department of Occupational and Environmental Health, Fujian Province Key lab of Environment and Health, Institution of Environment and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, China
Wei LIN
Department of Occupational and Environmental Health, Fujian Province Key lab of Environment and Health, Institution of Environment and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, China
Chenzi ZHANG
Department of Occupational and Environmental Health, Fujian Province Key lab of Environment and Health, Institution of Environment and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, China
Bin HUANG
Department of Occupational and Environmental Health, Fujian Province Key lab of Environment and Health, Institution of Environment and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, China

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Abstract

The present study aimed to determine the role of paraquat (PQ) in the NF-E2-related factor-2 (Nrf2) / heme oxygenase 1 (HO-1) pathway activation and the possible neuroprotective effects of tert-butylhydroquinone (tBHQ) pretreatment on PQ-induced neurodegeneration in vivo and in vitro. Treatment with PQ 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 tBHQ significantly attenuated behavioral performance impairment, the decrease in TH-positive neurons, and the increase in TUNEL-positive cells in the substantia nigra, as well as increased the protein expression of both nuclear Nrf2 and HO-1. In PC12 cells, pretreatment with tBHQ protected against PQ-mediated cytotoxicity. The dual-luciferase reporter gene also revealed the transcriptional activation of the HO-1 gene expression of antioxidant responsive element via Nrf2 as a consequence of PQ exposure. Collectively, these results clearly indicated for the first time that the Nrf2/HO-1 pathway in dopaminergic nigra was activated by PQ, and pretreatment with tBHQ conferred neuroprotection against PQ-induced Parkinsonism probably by increasing Nrf2 and HO-1 expression. This work was supported by National Natural Science Foundation in China (Grant 30800936, 81172715) and by Program for New Century Excellent Talents in Fujian Province University (NCETFJ).
Keywords: Paraquat; Neurodegeneration; tert-Butylhydroquinone (tBHQ); NF-E2-related factor 2 (Nrf2); Heme oxygenase 1 (HO-1)

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