Acute Fe-dextran treatment and redox balance in rat whole brain and cortex

Abstract

An acute Fe-dextran treatment produced oxidative stress in rat brain that lead to the translocation of Nrf2 to the cell nucleus, producing the activation of genes involved in the glutathione metabolism in the cellular environment. Previous reports have shown that the acute Fe overload produced by a single injection of Fe-dextran resulted in a significant decrease in total thiol and glutathione content in rat cortex area after 6 and 8 h post injection (pi). In the whole brain, enzymatic activities of glutathione-S-transferase (GST) and glutathione peroxidase (GPx), and total thiol content were increased as compared to control tissues at 6 or 8 h pi, respectively. The aim of this study was to determine the effect of acute Fe overload on glutathione-dependent enzymatic metabolism in cortex rat brain. A single dose of 500 mg Fe-dextran/kg body weight was administrated intraperitoneally to male Sprague Dawley rats. Total brain samples or cortex area were obtained from control and treated animals after 6 or 8 h pi. Glutathione reductase (GR) was determined spectrophotometrically. Reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) content were determined by reverse phase HPLC. MDA content showed a significant increased (p<0.05) at 8 h pi in whole brain. A significant decrease in cortical GSH (p<0.05), and a significant increase in cortical GSSG (p<0.05) was observed at 8 h pi. A slight but non-significant reduction in the activity of the enzyme GR was seen at 6 and 8 h pi in brain cortex. Taking as a whole, these results suggested that the increase in the GSSG/GSH ratio could be associated to the increase in the activities of GST and GPx without any change in GR activity in brain cortex. Moreover, it seems that the alteration in the redox status caused by the Fe treatment in the cortex could contribute to the lipid peroxidation changes detected in the whole brain.