Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response.
Zheng, Yi a,b; Tao, Shasha b; Lian, Fangru c; Chau, Binh T. d; Chen, Jie a; Sun, Guifan a; Fang, Deyu e; Lantz, Clark R. d,f; Zhang, Donna D. b,f,*
[Article]
Toxicology & Applied Pharmacology.
265(3):292-299, December 2012.
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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.
(C) 2012Elsevier, Inc.