Nrf2 protects against As(III)-induced damage in mouse liver and bladder

Toxicol Appl Pharmacol. 2009 Oct 1;240(1):8-14. doi: 10.1016/j.taap.2009.06.010. Epub 2009 Jun 16.


Arsenic compounds are classified as toxicants and human carcinogens. Environmental exposure to arsenic imposes a big health issue worldwide. Arsenic elicits its toxic efforts through many mechanisms, including generation of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls expression of a main cellular antioxidant response, which is required for neutralizing ROS and thus defending cells from exogenous insults. Previously, we demonstrated a protective role of Nrf2 against arsenic-induced toxicity using a cell culture model. In this report, we present evidence that Nrf2 protects against liver and bladder injury in response to six weeks of arsenic exposure in a mouse model. Nrf2(-/-) mice displayed more severe pathological changes in the liver and bladder, compared to Nrf2(+/+) mice. Furthermore, Nrf2(-/-) mice were more sensitive to arsenic-induced DNA hypomethylation, oxidative DNA damage, and apoptotic cell death. These results indicate a protective role of Nrf2 against arsenic toxicity in vivo. Hence, this work demonstrates the feasibility of using dietary compounds that target activation of the Nrf2 signaling pathway to alleviate arsenic-induced damage.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arsenites / toxicity*
  • Chemical and Drug Induced Liver Injury
  • Liver Diseases / genetics
  • Liver Diseases / metabolism
  • Liver Diseases / prevention & control*
  • Mice
  • Mice, Knockout
  • NF-E2-Related Factor 2 / deficiency
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / physiology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Sodium Compounds / toxicity*
  • Urinary Bladder Diseases / chemically induced
  • Urinary Bladder Diseases / genetics
  • Urinary Bladder Diseases / metabolism
  • Urinary Bladder Diseases / prevention & control*


  • Arsenites
  • NF-E2-Related Factor 2
  • Sodium Compounds
  • sodium arsenite