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

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

Research output: Contribution to journalArticle

64 Citations (Scopus)

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

Fingerprint

Arsenic
Liver
Urinary Bladder
Toxicity
Reactive Oxygen Species
Arsenicals
Poisons
DNA
Environmental Exposure
Cell death
Cell culture
Carcinogens
DNA Damage
Cell Death
Transcription Factors
Cell Culture Techniques
Antioxidants
Chemical activation
Health
Wounds and Injuries

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Nrf2 protects against As(III)-induced damage in mouse liver and bladder. / Jiang, Tao; Huang, Zheping; Chan, Jefferson Y.; Zhang, Donna.

In: Toxicology and Applied Pharmacology, Vol. 240, No. 1, 01.10.2009, p. 8-14.

Research output: Contribution to journalArticle

Jiang, Tao ; Huang, Zheping ; Chan, Jefferson Y. ; Zhang, Donna. / Nrf2 protects against As(III)-induced damage in mouse liver and bladder. In: Toxicology and Applied Pharmacology. 2009 ; Vol. 240, No. 1. pp. 8-14.
@article{cbaf9bc91358435aa4bcb848a3dc28ce,
title = "Nrf2 protects against As(III)-induced damage in mouse liver and bladder",
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.",
keywords = "Arsenic, As(III), Nrf2, Oxidative Stress, ROS",
author = "Tao Jiang and Zheping Huang and Chan, {Jefferson Y.} and Donna Zhang",
year = "2009",
month = "10",
day = "1",
doi = "10.1016/j.taap.2009.06.010",
language = "English (US)",
volume = "240",
pages = "8--14",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Nrf2 protects against As(III)-induced damage in mouse liver and bladder

AU - Jiang, Tao

AU - Huang, Zheping

AU - Chan, Jefferson Y.

AU - Zhang, Donna

PY - 2009/10/1

Y1 - 2009/10/1

N2 - 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.

AB - 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.

KW - Arsenic

KW - As(III)

KW - Nrf2

KW - Oxidative Stress

KW - ROS

UR - http://www.scopus.com/inward/record.url?scp=69749108385&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69749108385&partnerID=8YFLogxK

U2 - 10.1016/j.taap.2009.06.010

DO - 10.1016/j.taap.2009.06.010

M3 - Article

C2 - 19538980

AN - SCOPUS:69749108385

VL - 240

SP - 8

EP - 14

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 1

ER -