Rat brain oxidative damage in iron and copper overloads

MUSACCO SEBIO, ROSARIO; FERRAROTTI, NIDIA; SAPORITO MAGRIÑÁ, CHRISTIAN; SEMPRINE, JIMENA; FUDA, JULIAN; TORTI, HORACIO; BOVERIS, ALBERTO; REPETTO, MARISA

METALLOMICS

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2014 vol. 6 p. 1410 - 1416

1756-5901

This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg/kg (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 g Fe/g and from 3.6 to 34 g Cu/g. Brain chemiluminescence (10 cps/cm2) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) at 38 μg Fe/g brain and 15 μg Cu/g brain, and with half time responses (t1/2) at 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased 56% and 31% with C50 of 40 μg Fe/g and 20 μg Cu/g and with t1/2 of 9 h and 14 h. Protein oxidation increased 45% for Fe with C50 at 40 μg Fe/g and 18% for Cu with 10 μg Cu/g and t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by a Haber-Weiss type HO? formation with subsequent oxidative damage.