Acute iron overload and oxidative stress in brain

PILONI NE; FERNANDEZ V.; VIDELA L.A; PUNTARULO S

TOXICOLOGY

ELSEVIER IRELAND LTD

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

0300-483X

An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidativestress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concen-tration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6 hafter Fe administration. In this in vivo Fe overload model, the ascorbyl (A?)/ascorbate (AH−) ratio, takenas oxidative stress index, was assessed. The A?/AH−ratio in brain was significantly higher in Fe-dextrangroup, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactivesubstances (TBARS) generation rate and lipid radical (LR?) content detected by Electron ParamagneticResonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values ofnuclear factor-kappaB deoxyribonucleic acid (NF B DNA) binding activity were significantly increased(30%) after 8 h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21 h afterFe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold)and striatum (2.9 fold), were found at 6 h after Fe administration. CAT activity was significantly increasedafter 8 h 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- B DNA binding activity, which may con-tribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CATactivity. Moreover, data shown here clearly indicate that even though Fe increased in several isolatedbrain 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, showedenhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR?genera-tion rate after 6 h of Fe overload. This information has potential clinical relevance, as it could be the keyto understand specific brain damage occurring in conditions of Fe overloadAn in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidativestress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concen-tration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6 hafter Fe administration. In this in vivo Fe overload model, the ascorbyl (A?)/ascorbate (AH−) ratio, takenas oxidative stress index, was assessed. The A?/AH−ratio in brain was significantly higher in Fe-dextrangroup, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactivesubstances (TBARS) generation rate and lipid radical (LR?) content detected by Electron ParamagneticResonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values ofnuclear factor-kappaB deoxyribonucleic acid (NF B DNA) binding activity were significantly increased(30%) after 8 h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21 h afterFe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold)and striatum (2.9 fold), were found at 6 h after Fe administration. CAT activity was significantly increasedafter 8 h 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- B DNA binding activity, which may con-tribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CATactivity. Moreover, data shown here clearly indicate that even though Fe increased in several isolatedbrain 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, showedenhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR?genera-tion rate after 6 h of Fe overload. This information has potential clinical relevance, as it could be the keyto understand specific brain damage occurring in conditions of Fe overload