title: Hepatic and Nephric NRF2 Pathway Up-Regulation, an Early Antioxidant Response, in Acute Arsenic-Exposed Mice.
abstract: Inorganic arsenic (iAs), a proven human carcinogen, damages biological systems through multiple mechanisms, one of them being reactive oxygen species (ROS) production. NRF2 is a redox-sensitive transcription factor that positively regulates the genes of encoding antioxidant and detoxification enzymes to neutralize ROS. Although NRF2 pathway activation by iAs has been reported in various cell types, however, the experimental data in vivo are very limited and not fully elucidated in humans. The present investigation aimed to explore the hepatic and nephric NRF2 pathway upregulation in acute arsenic-exposed mice in vivo. Our results showed 10 mg/kg NaAsO₂ elevated the NRF2 protein and increased the transcription of Nrf2 mRNA, as well as up-regulated NRF2 downstream targets HO-1, GST and GCLC time- and dose-dependently both in the liver and kidney. Acute NaAsO₂ exposure also resulted in obvious imbalance of oxidative redox status represented by the increase of GSH and MDA, and the decrease of T-AOC. The present investigation reveals that hepatic and nephric NRF2 pathway expression is an early antioxidant defensive response upon iAs exposure. A better knowledge about the NRF2 pathway involvment in the cellular response against arsenic could help improve the strategies for reducing the cellular toxicity related to this metalloid.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110013, China. lijinlong2201751@163.com.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110013, China. duanxiaoxu1987@sina.com.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110013, China. woddd1986@126.com.|Cao County Center for Disease Control and Prevention, Heze 274400, China. woddd1986@126.com.
authors.forename: Dandan
authors.initials: D
authors.lastname: Dong
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110013, China. zhangyang521516@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110013, China. liwei09070710@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110013, China. m13072474706@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110013, China. nhflzm@163.com.
authors.forename: Huifang
authors.initials: H
authors.lastname: Nie
authors.affiliation: Environment and Non-Communicable Diseases Research Center, School of Public Health, China Medical University, Shenyang 110013, China. sungf@mail.cmu.edu.cn.
authors.forename: Guifan
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110013, China. libing@mail.cmu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001149:Arsenates / Q000633:toxicity; D001151:Arsenic / Q000633:toxicity*; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D023382:Toxicity Tests, Acute; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001149:Arsenates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C009277:sodium arsenate; D001151:Arsenic
keywords: NRF2; ROS; arsenic; kidney; liver