Induction of hepatic and renal metallothionein synthesis by ferric nitrilotriacetate in mice: the role of MT as an antioxidant

Journal Article · Fri Apr 01 04:00:00 EST 2005 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2004.08.014· OSTI ID:20721772

Min, Kyong-Son ^[1]; Morishita, Fumio ^[1]; Tetsuchikawahara, Noriko ^[1]; Onosaka, Satomi ^[1]

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1. 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, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 204; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIOXIDANTS
BIOLOGICAL STRESS
BIOSYNTHESIS
GLUTATHIONE
IRON CHLORIDES
KIDNEYS
LIVER
LYMPHOKINES
METALLOTHIONEIN
MICE
NTA
ZINC SULFATES