Depletion of glutathione system enzymes of the liver and erythrocytes in a rat model of acute iron poisoning.
ABSTRACT The proposed mechanism of iron-induced hepatotoxicity is free radical formation. It was hypothesized that the glutathione system of the liver and erythrocytes will be affected by acute iron poisoning. Male Wistar rats, 6-8 weeks of age, were assigned to one of three groups. Group I received distilled water, group II received 400 mg/kg elemental iron, and group III received 750 mg/kg elemental iron. All groups were gavage fed. Iron concentration, glutathione, and glutathione system enzymes were then measured in the liver and erythrocytes. The hepatic level of reduced glutathione (GSH) was significantly lower in groups II (3.1 +/- 4.6 mumol/mg protein) and III (4.7 +/- 4.6 mumol/mg protein) in comparison with group I (11.5 +/- 6.2 mumol/mg protein) (p < 0.001). Hepatic levels of glutathione S-transferase (GST) were higher and glutathione peroxidase (GPX) levels were lower in group III compared to groups II and I (p < 0.001 and p < 0.001). Compared to group I, glutathione reductase (GR) was lower in groups II and III (p < 0.001). There was no correlation between GSH, oxidized glutathione (GSSG), GST, GR, and GPX levels in the erythrocytes and in the liver (p = 0.41, p = 0.48, p = 0.49, p = 0.53, p = 01.4, and p = 0.84, respectively). In conclusion, acute iron intoxication in rats is associated with depletion of reduced glutathione in the liver.
Weinbaum
Sarit
S
Clinical Pharmacology and Toxicology Unit, Assaf-Harofeh Medical Center, Zerifin, Israel.
Kozer
Eran
E
Evans
Sandra
S
Bar-Haim
Adina
A
Zandback
Yehudit
Y
Lahat
Eli
E
Petrov
Irena
I
Alkan
Yoav
Y
Siman-Tov
Yariv
Y
Rechavi
Moshe
M
Goldstein
Leeh
L
Berkovitch
Matitiahu
M