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

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

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Department of Pharmacology and Toxicology, University of Arizona, 1703 E. Mabel St., Tucson, AZ 85721, USA.


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.

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