title: Induction of hepatic and renal metallothionein synthesis by ferric nitrilotriacetate in mice: the role of MT as an antioxidant.
abstract: Metallothionein (MT) demonstrates strong antioxidant properties, yet the physiological relevance of its antioxidant action is not clear. Injection of mice with ferric nitrilotriacetate (Fe-NTA) caused a dose-dependent increase in hepatic and renal MT. Fe-NTA caused a greater increase in hepatic and renal MT concentration (2.5- and 4-fold) compared with FeCl(3) at the same dose of ferric ion. MT mRNA levels were markedly elevated in both of tissues. Thiobarbituric acid (TBA) values in both tissues reached a maximum after 2-4 h. The MT concentrations were significantly increased after 2-4 h in liver and after 8-16 h in kidneys. Plasma concentrations of cytokines such as IL-6 and TNFalpha were elevated by 4 h; IL-6 levels were 24 times higher after Fe-NTA than that after injection of FeCl(3). Pretreatment of mice with ZnSO(4) attenuated nephrotoxicity induced by Fe-NTA after 2 h, but was not effective 4 h after injection. After a Fe-NTA injection, a loss of Cd-binding properties of preinduced MT was observed only in kidneys of Zn-pretreated mice but not in liver. Treatment with BSO, glutathione (GSH) depletor, intensified a loss of its Cd-binding properties after a Fe-NTA injection. These results indicate that induction of MT synthesis may result from reactive oxygen species (ROS) generated by Fe-NTA, and MT may act in vivo as a complementary antioxidant.
authors.affiliation: Faculty of Nutrition, Kobe Gakuin University, Ikawadani-cho, Kobe, 651-2180, Japan. min@nutr.kobegakuin.ac.jp
authors.forename: Kyong-Son
authors.initials: KS
authors.lastname: Min
authors.forename: Fumio
authors.initials: F
authors.lastname: Morishita
authors.forename: Noriko
authors.initials: N
authors.lastname: Tetsuchikawahara
authors.forename: Satomi
authors.initials: S
authors.lastname: Onosaka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001729:Bismuth; D001806:Blood Urea Nitrogen; D001959:Bromates / Q000633:toxicity; D002104:Cadmium / Q000378:metabolism; D002712:Chlorides; D005290:Ferric Compounds / Q000008:administration & dosage / Q000633:toxicity*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000633:toxicity*; D009571:Nitrilotriacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis; D015032:Zinc
chemical_list: D000975:Antioxidants; D001959:Bromates; D002712:Chlorides; D005290:Ferric Compounds; D015850:Interleukin-6; D009153:Mutagens; D014409:Tumor Necrosis Factor-alpha; D002104:Cadmium; C019536:potassium bromate; D008668:Metallothionein; D015032:Zinc; D009571:Nitrilotriacetic Acid; D001729:Bismuth; C024555:ferric chloride; C020326:ferric nitrilotriacetate