title: Acute iron overload and oxidative stress in brain.
abstract: An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A)/ascorbate (AH(-)) ratio, taken as oxidative stress index, was assessed. The A/AH(-) ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6h after Fe administration. CAT activity was significantly increased after 8h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR generation rate after 6h of Fe overload. This information has potential clinical relevance, as it could be the key to understand specific brain damage occurring in conditions of Fe overload.
authors.affiliation: Physical Chemistry-Institute of Biochemistry and Molecular Medicine (IBIMOL), School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina.
authors.forename: Natacha E
authors.initials: NE
authors.lastname: Piloni
authors.forename: Virginia
authors.initials: V
authors.lastname: Fermandez
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
authors.forename: Susana
authors.initials: S
authors.lastname: Puntarulo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000378:metabolism*; D007505:Iron-Dextran Complex / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D016328:NF-kappa B; D017392:Thiobarbituric Acid Reactive Substances; D007505:Iron-Dextran Complex; D004247:DNA; D007501:Iron; D002374:Catalase; D001205:Ascorbic Acid
keywords: 2,2,5,5-tetramethyl piperidine-1-oxyl; A; AH(−); Brain; CA; CAT; DF; DHA; DMSO; DNA; EPR; Electron Paramagnetic Resonance; Free radicals; Ft; H(2)O(2); Iron; LIP; LR; N-t-butyl-α-phenyl nitrone; NF-κB; O(2); O(2)(−); OH; PBN; ROS; SOD; TBARS; TEMPO; TGA; alpha tocopherol; ascorbate; ascorbyl radical; calcein; catalase; deferoxamine mesylate; dehydroascorbic acid; deoxyribonucleic acid; dimethyl sulfoxide; ferritin; hydrogen peroxide; hydroxyl radical; labile iron pool; lipid derived radicals; nuclear factor kappa B; oxidative stress; oxygen; reactive oxygen species; superoxide anion; superoxide dismutase; thiobarbituric acid reactive substances; thioglycolique acid; α-T