Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

PERAZZO JUAN CARLOS; SUSANA PUNTARULO; VIRGINIA FERNANDEZ; NATACHA E PILONI; LUIS A VIDELA

BIOMETALS

SPRINGER

Lugar: Berlin; Año: 2016 vol. 29 p. 119 - 130

0966-0844

Abstract This work was aimed to test the hypothesisthat sub-chronic administration of iron-dextran (Fedextran)(six doses of 50 mg Fe-dextran/kg) to ratstriggers a transient oxidative stress in brain andmechanisms of cellular antioxidant defence. After2 h of administration of the 6th dose, a significantincrease of total Fe, the labile Fe pool (LIP), the lipidradical (LR?)/a-tocopherol (a-T) content ratio wereobserved, as compared to values in control brainhomogenates. The ascorbyl radical (A?)/ascorbate(AH-) content ratio and the oxidation rate of 20,70-dichlorodihidrofluorescein (DCFH-DA) were signifi-cantly higher in Fe-dextran treated rats, as comparedto values in brain from control rats after 4 h treatment.An increase in both catalase (CAT) and superoxidedismutase (SOD) activity was observed at 8 and 1?2 h,respectively. No significant changes were detected inthe nuclear factor-jB (NF-kappaB) levels in nuclearextracts from rat brains after 1?8 h of Fe-dextranadministration. After 2 h of Fe administration Feconcentration in cortex, striatum and hippocampuswas significantly increased as compared to the sameareas from control animals. Both, CAT and SODactivities were significantly increased in cortex afterFe administration over control values, withoutchanges in striatum and hippocampus. Taken as awhole, sub-chronic Fe administration enhances thesteady state concentration of Fe in the brain LIP thatfavors the settlement of an initial oxidative stresscondition, both at hydrophilic and lipophilic compartments,resulting in cellular protection evidenced byantioxidant enzyme upregulation.