A possible role of Nrf2 in prevention of renal oxidative damage by ferric nitrilotriacetate

Keita Kanki, Takashi Umemura, Yasuki Kitamura, Yuji Ishii, Yuichi Kuroiwa, Yukio Kodama, Ken Itoh, Masayuki Yamamoto, Akiyoshi Nishikawa, Masao Hirose

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)353-361
Number of pages9
JournalToxicologic Pathology
Issue number2
Publication statusPublished - 2008 Feb
Externally publishedYes


  • Fe-NTA
  • Kidney
  • Nrf2
  • Oxidative stress

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology


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