IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Brain antioxidant response to iron and copper acute intoxications in rats.
Autor/es:
SEMPRINE, JIMENA; FERRAROTTI, NIDIA; MUSACCO-SEBIO, ROSARIO; SAPORITO-MAGRIÑÁ, CHRISTIÁN; CASTRO-PARODI MAURICIO; DAMIANO ALICIA E; FUDA, JULIÁN; TORTI, HORACIO; BOVERIS, ALBERTO; REPETTO, MARISA
Lugar:
Chascomus
Reunión:
Congreso; 4th Latino American Meeting on Biological Inorganic Chemistry; 2014
Resumen:
The transition metals Fe and Cu are required for mammalian aerobic brain metabolism, but intakes higher than 25 mg Fe/day and 10 mg Cu/day are toxic. The brain toxicity produced by Fe and Cu overloads encompasses multiple simultaneous chemical pathways involving oxidative reactions, most of them free-radical mediated reactions. Recent studies described rat liver and brain oxidative damages after an acute toxic load of Fe or Cu in kinetic terms considering the time (t1/2) and the organ metal content (C50) that produced half maximal oxidative effects. The thiol redox hypothesis extended the classical concept of oxidative stress4 to the disruption of redox signaling and regulation due to a redox shift of ?SH to ?SS- groups. The redox state of the thiol groups in glutathione, thioredoxin and other low molecular weight thiols equilibrate with the ?SH/?SS- ratio in proteins and regulatory factors and is consequently deeply involved in cell signaling and regulation. The current interpretation of cellular oxidative stress is that the condition implies an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control. In the liver the increase in oxidants, usually free radicals and related species, and the shift in the ?SH/-SS- redox couple occur simultaneously and have synergic effects. The same process is described here for the brain, situation that if sustained leads to molecular and cellular damage and eventually to neuronal death. The aim of this work is to analyze the time course of the antioxidant response in rat brain after toxic Fe and Cu overloads, a process that produces oxidative stress and oxidative damage in neurons and in the brain. Rat brain dose- and time-dependent antioxidant responses to Fe and Cu overloads (0-60 mg/g) are described by C50 and t1/2, the brain metal content and the time for half maximal oxidative responses. The GSH/GSSG ratio was the most sensitive indicator of brain oxidative stress. The decrease in GSH and the increase of in vivo brain chemiluminescence (BC) had similar time courses. The C50 were in similar ranges, which indicates a unique free-radical mediated process for each metal. Rat brain dose- and time-dependent antioxidant responses to Fe and Cu overloads (0-60 mg/g) are described by C50 and t1/2, the brain metal content and the time for half maximal oxidative responses. The GSH/GSSG ratio was the most sensitive indicator of brain oxidative stress. The decrease in GSH and the increase of in vivo brain chemiluminescence (BC) had similar time courses. The C50 were in similar ranges, which indicates a unique free-radical mediated process for each metal