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

Toxicol Appl Pharmacol. 2012 Dec 15;265(3):292-9. doi: 10.1016/j.taap.2012.08.028. Epub 2012 Sep 6.

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.

Publication types

  • Research Support, N.I.H., Extramural

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*

Substances

  • Cytokines
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Thiocyanates
  • RNA
  • sulforafan
  • Arsenic