Title: Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response.

Authors: Zheng, Yi; Tao, Shasha; Lian, Fangru; Chau, Binh T; Chen, Jie; Sun, Guifan; Fang, Deyu; Lantz, R Clark; Zhang, Donna D

Published In Toxicol Appl Pharmacol, (2012 Dec 15)

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.

PubMed ID: 22975029

MeSH Terms: Animals; Arsenic/toxicity*; Bronchoalveolar Lavage Fluid/cytology; Bronchoalveolar Lavage Fluid/immunology; Cytokines/genetics; Cytokines/immunology; DNA Damage; Immunohistochemistry; Inhalation Exposure/adverse effects*; Isothiocyanates; Lung Injury/chemically induced*; Lung Injury/immunology; Lung Injury/prevention & control*; Mice; Mice, Knockout; NF-E2-Related Factor 2/genetics; NF-E2-Related Factor 2/immunology*; RNA/chemistry; RNA/genetics; Reverse Transcriptase Polymerase Chain Reaction; Thiocyanates/pharmacology*