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Tert-Butylhydroquinone as a Phenolic Activator of Nrf2 Antagonizes Arsenic-Induced Oxidative Cytotoxicity but Promotes Arsenic Methylation and Detoxication in Human Hepatocyte Cell Line

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Abstract

Oxidative stress plays crucial roles in exerting a variety of damages upon arsenic exposure. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master transcriptional regulator protecting cells and tissues from oxidative injuries. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a well-known synthetic Nrf2 inducer, could protect human hepatocytes against arsenic-induced cytotoxicity and oxidative injuries. Our results showed that 5 and 25 μmol/l tBHQ pretreatment suppressed the arsenic-induced hepatocellular cytotoxicity, reactive oxygen species generation, and hepatic lipid peroxidation, while relieved the arsenic-induced disturbances of intracellular glutathione balance. In addition, we also observed that tBHQ treatment promoted the arsenic biomethylation process and upregulated Nrf2-regulated downstream heme oxygenase-1 and NADPH: quinine oxidoreductase 1 mRNA expressions. Collectively, we suspected that Nrf2 signaling pathway may be involved in the protective effects of tBHQ against arsenic invasion in hepatocytes. These data suggest that phenolic Nrf2 inducers, such as tBHQ, represent novel therapeutic or dietary candidates for the population at high risk of arsenic poisoning.

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Acknowledgments

This study was supported by grants from National Natural Science Foundation of China (NSFC, No. 81172611).

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Authors and Affiliations

  1. Department of Occupational and Environmental Health, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, 92 North 2nd Road, Heping District, Shenyang, 110001, China

    Xiaoxu Duan, Dan Liu, Jinlong Li, Shuo Zhao, Huifang Nie, Yang Zhang, Guifan Sun & Bing Li

  2. Student Office, China Medical University, Shenyang, 110001, China

    Xiaoyue Xing

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  1. Xiaoxu Duan
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  2. Dan Liu
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Correspondence to Bing Li.

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Duan, X., Liu, D., Xing, X. et al. Tert-Butylhydroquinone as a Phenolic Activator of Nrf2 Antagonizes Arsenic-Induced Oxidative Cytotoxicity but Promotes Arsenic Methylation and Detoxication in Human Hepatocyte Cell Line. Biol Trace Elem Res 160, 294–302 (2014). https://doi.org/10.1007/s12011-014-0042-4

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