title: Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response.
abstract: Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted in pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure.
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Shasha
authors.initials: S
authors.lastname: Tao
authors.forename: Fangru
authors.initials: F
authors.lastname: Lian
authors.forename: Binh T
authors.initials: BT
authors.lastname: Chau
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Guifan
authors.initials: G
authors.lastname: Sun
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
authors.forename: R Clark
authors.initials: RC
authors.lastname: Lantz
authors.forename: Donna D
authors.initials: DD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004249:DNA Damage; D007150:Immunohistochemistry; D019570:Inhalation Exposure / Q000009:adverse effects*; D017879:Isothiocyanates; D055370:Lung Injury / Q000139:chemically induced* / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000276:immunology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D013861:Thiocyanates; D012313:RNA; C016766:sulforaphane; D001151:Arsenic