Nrf2 protects against As(III)-induced damage in mouse liver and bladder.
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.
Jiang
Tao
T
Department of Pharmacology and Toxicology, University of Arizona, 1703 E. Mabel St., Tucson, AZ 85721, USA.
Huang
Zheping
Z
Chan
Jefferson Y
JY
Zhang
Donna D
DD
D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017670:Sodium Compounds / Q000633:toxicity*; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
D018053:Arsenites; D051267:NF-E2-Related Factor 2; D017670:Sodium Compounds; C017947:sodium arsenite