CONICET | Buscador de Institutos y Recursos Humanos

The time course of the genomic response that involves the expression of SOD1, catalase and Nrf2 in rat brain was evaluated in the period of 0-24 h after iron (Fe) and copper (Cu) ions loads. The molecule that seems most likely to be the signal for the genomic transcription is a soluble phospholipid hydroperoxide (ROOH), where R indicates a 4-6 carbon chain, that immediately increases its steady state concentration along with the increased rates of lipid peroxidation. The hypothesis is that the activation of Nrf2-ARE signaling pathway, one of the physiologic mechanisms in cellular defense against oxidative stress that controls the expression of genes whose proteins products, is involved in detoxification and elimination of reactive oxidants and by enhancing cellular antioxidant content. The aim of the present study was to determine the characteristics of the adaptive response in rat brain after Fe and Cu ions overloads. The activities and expressions of brain cytosolic superoxide dismutase (SOD1), and catalase were determined as well as the levels of the regulatory transcription factor Nrf2 in the cytosol and nucleus. The ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) was determined as a reflection of the ?SH/-SS- ratio of regulatory control proteins of neuronal metabolism and function. Rats (220 ± 8 g) were given single doses of 13.5 mg FeSO4/100 g or of 2.8 mg CuSO4/100 g and the brain response to these overdoses was followed. SOD1, catalase, glutathione transferase and Nrf2 increased their activities/expressions in an adaptive response to oxidative stress: after 24 h of Fe and Cu administration, expression was increased: SOD1, 2.5 and 1.8 times; catalase 2 and 2.5 times (p