Acute iron overload and oxidative stress in brain

NATACHA E PILONI; VIRGINIA FERNANDEZ; LUIS A VIDELA; NATACHA E. PILONI Y SUSANA PUNTARULO

TOXICOLOGY

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2013 vol. 314 p. 174 - 182

0300-483X

Fe excess is believed to generate oxidative stress, understood as an increase in the steady state concentration of reactive oxygen and nitrogen species. An in vivo model in rat was developed by ip administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Brain Fe levels from rats subjected to Fe-overload were markedly higher than the control values, and so did the LIP content 6 h after Fe administration. The ascorbyl (A?)/ascorbate (AH-) ratio, taken as oxidative index, was studied under the in vivo Fe overload conditions. The A?/AH− ratio in brain was significantly higher in Fe-dextran treated rats as compared to values in brain from control rats. Lipid damage was tested both, as TBARS generation rate, and electron paramagnetic resonance (EPR) detection of lipid radicals (LR?) in brain from Fe-dextran supplemented rats. Neither of them were significantly different from values in control brains. However, NFκB activation was significanltly increased (30%) after 6 h of Fe administration, and CAT activity was enhanced by 62% 21 h after the treatment. Fe content in cortex, hippocampus and striatum was increased by 241, 156 and 295%, respectively at 6 h after Fe administration. However, LR? generation rate only increased significantly in brain cortex after Fe overload (two-fold). CAT activity was significantly increased after 8 h of Fe administration in cortex, hippocampus and striatum (141, 86, and 47%, respectively). Fe response in the whole brain seems related to NF-κB DNA binding capacity that may contribute to limit ROS-dependent damage by an effect on the activity of the antioxidant enzyme CAT. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, Fe content in striatum was more drastically enhanced than in cortex and hippocampus. Nevertheless, the comparison among the net increase in LR? generation rate in the brain areas showed that in cortex lipid peroxidation was significantly increased, meanwhile LR? generation rate was not changed after 6 h of Fe overload in striatum and hippocampus. This information could be of interest from the clinical point of view, since it could be the key to understand the reason for specific brain damage that could occur under these conditions.