Toxicologic Pathology

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here for more information

Click here for more information

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
0192623307311401v1
36/2/353    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Google Scholar
Right arrow Articles by Kanki, K.
Right arrow Articles by Hirose, M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kanki, K.
Right arrow Articles by Hirose, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
This version was published on February 1, 2008
Toxicologic Pathology, Vol. 36, No. 2, 353-361 (2008)
DOI: 10.1177/0192623307311401
© 2008 Society of Toxicologic Pathology

Invited Review

A Possible Role of Nrf2 in Prevention of Renal Oxidative Damage by Ferric Nitrilotriacetate

Keita Kanki1, Takashi Umemura1, Yasuki Kitamura1, Yuji Ishii1, Yuichi Kuroiwa1, Yukio Kodama2, Ken Itoh3, Masayuki Yamamoto4, Akiyoshi Nishikawa1 and Masao Hirose1

1 Division of Pathology and
2 Division of Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan;
3 Center for Advanced Medical Research, School of Medicine, Hirosaki University, 5 Zaihu-cho, Hirosaki-shi, Aomori, Japan and
4 Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tennoudai, Tsukuba 305, Ibaraki, Japan

Correspondence: Address correspondence to: Takashi Umemura, Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan; e-mail: umemura{at}nihs.go.jp.

To ascertain the possible roles of nuclear erythroid 2 p45-related factor 2 (Nrf2), a key transcription factor of phase 2 drug-metabolizing enzymes, in renal cellular defense against oxidative stress, wild-type and Nrf2-knockout (–/–) mice were treated with ferric nitrilotriacetate (Fe-NTA) at doses of 3 or 6 mg iron/kg body weight. After Fe-NTA treatment, Nrf2 (–/–) mice consistently showed lower levels of glutathione (GSH) in the kidney at the low dose and the liver at the high dose than the wild-type mice. Gamma-glutamylcysteine ligase (GCL) activity in the kidney and liver of Nrf2 (–/–) mice was also consistently lower than in wild-type mice after the Fe-NTA treatment. Histopathological examination revealed that nephrotoxicity of Fe-NTA, reflected in necrosis of renal tubule epithelial cells following nuclear damage, was more severe in the Nrf2 (–/–) mice than in their wild-type counterparts. Overall, the data suggest that Nrf2 (–/–) mice are unable to compensate for depletion of renal GSH because of oxidative stress, being more susceptible to Fe-NTA-induced nephrotoxicity. In conclusion, the present study showed that Nrf2 might play an important role in protecting cells from oxidative stress in the kidney through its regulation of antioxidant enzymes.

Key Words: Fe-NTA • Nrf2 • kidney • oxidative stress

Abbreviations: ARE, antioxidant-response element • Fe-NTA, ferric nitrilotri-acetate • GCL, gamma-glutamylcysteine ligase • GSH, glutathione • GSS, glutathione synthetase • H&E, hematoxylin and eosin • Keap1, Kelch-like ECH-associated protein 1 • NDA, 2 3-naphthalenedicarboxyaldehyde • MDA, malondialdehyde • Nrf2, nuclear erythroid 2 p45-related factor 2 • ROS, reactive oxygen species • TBARS, thiobarbituric acid-reactive substances • PCR, polymerase chain reaction


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?