title: Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.
abstract: Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid.
authors.affiliation: 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, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110013, Liaoning Province, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110013, Liaoning Province, People's Republic of China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Duan
authors.affiliation: 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, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110013, Liaoning Province, People's Republic of China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.affiliation: 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, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110013, Liaoning Province, People's Republic of China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhao
authors.affiliation: 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, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110013, Liaoning Province, People's Republic of China.|Health Care Department, Maternal and Child Health Care Center of Cangzhou, Hebei, 061000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: 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, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110013, Liaoning Province, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: 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, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110013, Liaoning Province, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: 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, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110013, Liaoning Province, People's Republic of China.
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, People's Republic of China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Sun
authors.affiliation: 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, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110013, Liaoning Province, People's Republic of China. libing@mail.cmu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001151:Arsenic / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D001151:Arsenic
keywords: Arsenic; Cerebral cortex; Hippocampus; NRF2; Oxidative stress