Induction of hepatic and renal metallothionein synthesis by ferric nitrilotriacetate in mice: the role of MT as an antioxidant
- Faculty of Nutrition, Kobe Gakuin University, Kobe, 651-2180 (Japan)
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{sub 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 TNF{alpha} were elevated by 4 h; IL-6 levels were 24 times higher after Fe-NTA than that after injection of FeCl{sub 3}. Pretreatment of mice with ZnSO{sub 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.
- OSTI ID:
- 20721772
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 204, Issue 1; Other Information: DOI: 10.1016/j.taap.2004.08.014; PII: S0041-008X(04)00395-3; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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