caa a22 4500 445321334 CHVBK 20180317142705.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10534-011-9471-0 doi (NATIONALLICENCE)springer-10.1007/s10534-011-9471-0 Effect of diquat-induced oxidative stress on iron metabolism in male Fischer-344 rats [Elektronische Daten] [Masashi Higuchi, Yasunaga Yoshikawa, Koichi Orino, Kiyotaka Watanabe] 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 20h after diquat treatment. Hepatic free iron levels increased markedly in the early stages following treatment and remained elevated for at least 6h, resulting in severe hepatotoxicity, until returning to control levels at 20h. The level of hepatic ferritin, especially the H-subunit, increased 20h 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 20h after diquat treatment, whereas the level of plasma interleukin-6 increased markedly at 3h and remained high until 20h. In the liver of diquat-treated rats, expression of hepcidin mRNA was markedly upregulated at 3 and 6h, whereas ferroportin mRNA expression was downregulated slightly at 20h. Transferrin receptor 1 mRNA expression was significantly upregulated at 3, 6, and 20h. 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. Springer Science+Business Media, LLC., 2011 Diquat nationallicence Iron metabolism nationallicence Oxidative stress nationallicence Rat nationallicence Higuchi Masashi Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, 034-8628, Towada, Aomori, Japan aut Yoshikawa Yasunaga Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, 034-8628, Towada, Aomori, Japan aut Orino Koichi Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, 034-8628, Towada, Aomori, Japan aut Watanabe Kiyotaka Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, 034-8628, Towada, Aomori, Japan aut BioMetals Springer Netherlands 24/6(2011-12-01), 1123-1131 0966-0844 24:6<1123 2011 24 10534 https://doi.org/10.1007/s10534-011-9471-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10534-011-9471-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Higuchi Masashi Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, 034-8628, Towada, Aomori, Japan aut NATIONALLICENCE 700 1- Yoshikawa Yasunaga Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, 034-8628, Towada, Aomori, Japan aut NATIONALLICENCE 700 1- Orino Koichi Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, 034-8628, Towada, Aomori, Japan aut NATIONALLICENCE 700 1- Watanabe Kiyotaka Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, 034-8628, Towada, Aomori, Japan aut NATIONALLICENCE 773 0- BioMetals Springer Netherlands 24/6(2011-12-01), 1123-1131 0966-0844 24:6<1123 2011 24 10534 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer