title: Tert-butylhydroquinone as a phenolic activator of Nrf2 antagonizes arsenic-induced oxidative cytotoxicity but promotes arsenic methylation and detoxication in human hepatocyte cell line.
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.
authors: 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.
authors: Xiaoxu
authors: X
authors: Duan
authors: Dan
authors: D
authors: Liu
authors: Xiaoyue
authors: X
authors: Xing
authors: Jinlong
authors: J
authors: Li
authors: Shuo
authors: S
authors: Zhao
authors: Huifang
authors: H
authors: Nie
authors: Yang
authors: Y
authors: Zhang
authors: Guifan
authors: G
authors: Sun
authors: Bing
authors: B
authors: Li
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001151:Arsenic / Q000378:metabolism / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000975:Antioxidants; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D020011:Protective Agents; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; C018855:2-tert-butylhydroquinone; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005980:Glutathione Reductase; D005978:Glutathione; D001151:Arsenic