title: Glutathione metabolizing enzymes and oxidative stress in ferric nitrilotriacetate mediated hepatic injury.
abstract: Glutathione (GSH) plays several important roles in the protection of cells against oxidative damage, particularly following exposure to xenobiotics. Ferric nitrilotriacetate (Fe-NTA) is a potent depletor of GSH and also enhances tissue lipid peroxidation. In this study, we show the effect of Fe-NTA treatment on hepatic GSH and some of the glutathione metabolizing enzymes, oxidant generation and liver damage. The level of hepatic GSH and the activities of glutathione reductase, glutathione S-transferase, glutathione peroxidase, and glucose 6-phosphate dehydrogenase all decrease following Fe-NTA administration. In these parameters the maximum decrease occurred at 12 h following Fe-NTA treatment. In contrast, γ-glutamyl transpeptidase was increased at this time. Not surprisingly, the increase in the activity of γ-glutamyl transpeptidase and decreases in GSH, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and glutathione S-transferase were found to be dependent on the dose of Fe-NTA administered. Fe-NTA administration also enhances the production of H2O2 and increases hepatic lipid peroxidation. Parallel to these changes, Fe-NTA enhances liver damage as evidenced by increases in serum transaminases. Once again, the liver damage is dependent on the dose of Fe-NTA and is maximal at 12 h. Pretreatment of animals with antioxidant, butylated hydroxy anisole (BHA), protects against Fe-NTA-mediated hepatotoxicity further supporting the involvement of oxidative stress in Fe-NTA-mediated hepatic damage. In aggregate, our results indicate that Fe-NTA administration eventuates in decreased hepatic GSH, a fall in the activities of glutathione metabolizing enzymes and excessive production of oxidants, all of which are involved in the cascade of events leading to iron-mediated hepatic injury.
authors.affiliation: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors.forename: M
authors.initials: M
authors.lastname: Iqbal
authors.affiliation: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors.forename: S D
authors.initials: SD
authors.lastname: Sharma
authors.affiliation: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors.forename: H
authors.initials: H
authors.lastname: Rezazadeh
authors.affiliation: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors.forename: N
authors.initials: N
authors.lastname: Hasan
authors.affiliation: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors.forename: M
authors.initials: M
authors.lastname: Abdulla
authors.affiliation: a Department of Medical Elementology and Toxicology , Jamia Hamdard (Hamdard University) , New Delhi , India.
authors.forename: M
authors.initials: M
authors.lastname: Athar