Induction of hepatic and renal metallothionein synthesis by ferric nitrilotriacetate in mice: the role of MT as an antioxidant.
Toxicol Appl Pharmacol
; 204(1): 9-17, 2005 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-15781289
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Férricos
/
Rim
/
Fígado
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Metalotioneína
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Mutagênicos
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Ácido Nitrilotriacético
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Antioxidantes
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Japão