Hepatic and Nephric NRF2 Pathway Up-Regulation, an Early Antioxidant Response, in Acute Arsenic-Exposed Mice

International Journal of Environmental Research and Public Health

Jinlong Li¹  Xiaoxu Duan¹  Dandan Dong¹  Yang Zhang¹  Wei Li¹  Lu Zhao¹  Huifang Nie¹  Guifan Sun²  Bing Li¹ 

[1] Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang 110013, China; E-Mails:;Environment and Non-Communicable Diseases Research Center, School of Public Health, China Medical University, Shenyang 110013, China; E-Mail:

关键词: arsenic;    ROS;    NRF2;    liver;    kidney;   

DOI  :  10.3390/ijerph121012628

来源: mdpi

【 摘 要 】

Inorganic arsenic (iAs), a proven human carcinogen, damages biological systems through multiple mechanisms, one of them being reactive oxygen species (ROS) production. NRF2 is a redox-sensitive transcription factor that positively regulates the genes of encoding antioxidant and detoxification enzymes to neutralize ROS. Although NRF2 pathway activation by iAs has been reported in various cell types, however, the experimental data in vivo are very limited and not fully elucidated in humans. The present investigation aimed to explore the hepatic and nephric NRF2 pathway upregulation in acute arsenic-exposed mice in vivo. Our results showed 10 mg/kg NaAsO₂ elevated the NRF2 protein and increased the transcription of Nrf2 mRNA, as well as up-regulated NRF2 downstream targets HO-1, GST and GCLC time- and dose-dependently both in the liver and kidney. Acute NaAsO₂ exposure also resulted in obvious imbalance of oxidative redox status represented by the increase of GSH and MDA, and the decrease of T-AOC. The present investigation reveals that hepatic and nephric NRF2 pathway expression is an early antioxidant defensive response upon iAs exposure. A better knowledge about the NRF2 pathway involvment in the cellular response against arsenic could help improve the strategies for reducing the cellular toxicity related to this metalloid.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.