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

Tao Jiang, Zheping Huang, Jefferson Y. Chan, Donna D. Zhang

Research output: Contribution to journalArticle

71 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8-14
Number of pages7
JournalToxicology and Applied Pharmacology
Volume240
Issue number1
DOIs
StatePublished - Oct 1 2009

Keywords

  • Arsenic
  • As(III)
  • Nrf2
  • Oxidative Stress
  • ROS

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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