Brain antioxidant response to iron and copper acute intoxication in rats

SEMPRINE, J; FERRAROTTI, N.; MUSACCO SEBIO, R; SAPORITO, C.; BOVERIS, A; REPETTO, M.; CASTRO PARODI, M; DAMIANO, A.; FUDA, J; TORTI, H.

Chascomus

Congreso; IV Congreso Latinoamericano de Química Bioinorgánica (IVLABIC); 2014

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 studies1,2,3 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- groups5. 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 regulation6. 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 control6. 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 effects3. 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.