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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.

Author information

1
Department of Pharmacology and Toxicology, University of Arizona, 1703 E. Mabel St., Tucson, AZ 85721, USA.

Abstract

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.

PMID:
19538980
PMCID:
PMC2739886
DOI:
10.1016/j.taap.2009.06.010
[Indexed for MEDLINE]
Free PMC Article

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