BioMetals

, Volume 24, Issue 6, pp 1123–1131 | Cite as

Effect of diquat-induced oxidative stress on iron metabolism in male Fischer-344 rats

  • Masashi Higuchi
  • Yasunaga Yoshikawa
  • Koichi Orino
  • Kiyotaka Watanabe
Article

Abstract

Diquat toxicity causes iron-mediated oxidative stress; however, it remains unclear how diquat affects iron metabolism. Here, we examined the effect of diquat-induced oxidative stress on iron metabolism in male Fischer-344 rats, with particular focus on gene expression. Hepatic nonheme iron content was unchanged until 20 h after diquat treatment. Hepatic free iron levels increased markedly in the early stages following treatment and remained elevated for at least 6 h, resulting in severe hepatotoxicity, until returning to control levels at 20 h. The level of hepatic ferritin, especially the H-subunit, increased 20 h after diquat treatment due to elevated hepatic ferritin-H mRNA expression. These results indicate that early elevated levels of free iron in the liver of diquat-treated rats cause hepatotoxicity, and that this free iron is subsequently sequestered by ferritin synthesized under conditions of oxidative stress, thus limiting the pro-oxidant challenge of iron. The plasma iron concentration decreased at 6 and 20 h after diquat treatment, whereas the level of plasma interleukin-6 increased markedly at 3 h and remained high until 20 h. In the liver of diquat-treated rats, expression of hepcidin mRNA was markedly upregulated at 3 and 6 h, whereas ferroportin mRNA expression was downregulated slightly at 20 h. Transferrin receptor 1 mRNA expression was significantly upregulated at 3, 6, and 20 h. These results indicate that inhibition of iron release from iron-storage tissues, through stimulation of the interleukin-6-hepcidin-ferroportin axis, and enhanced iron uptake into hepatocytes, mediated by transferrin receptor 1, cause hypoferremia.

Keywords

Diquat Iron metabolism Oxidative stress Rat 

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Masashi Higuchi
    • 1
  • Yasunaga Yoshikawa
    • 1
  • Koichi Orino
    • 1
  • Kiyotaka Watanabe
    • 1
  1. 1.Laboratory of Veterinary Biochemistry, School of Veterinary MedicineKitasato UniversityTowadaJapan

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