Gestational caloric restriction improves redox homeostasis parameters in the brain of Wistar rats: a screening from birth to adulthood.

Caloric restriction (CR) improves health and life span in animal models. Although CR effects in adult life are well described, little is known about effects on offspring when applied during gestation. Pregnancy is a remarkable period of life, alterations in this stage lead to lifelong consequences, some of which, associated to redox unbalance. Furthermore, gestational overweight is a growing issue that can lead to detrimental outcomes. To address this issue, we divided pregnant rats into control (ad libitum food) and CR groups, which received 20% less food than control. Micronutrients consumption was equalized between groups by oral gavage. Cerebellum, prefrontal cortex, hippocampus, and hypothalamus were evaluated on post-natal day (PND) 0, 7, 21, and 60. We observed increased oxidants content on PND0 in all brain structures, except for the cerebellum. Key enzymatic antioxidant defenses showed decreased activity on PND0. Interestingly, on PND60, we observed a positive modulation of most antioxidant enzymes, especially on the prefrontal cortex and hippocampus. Non-enzymatic antioxidant defenses were decreased at birth and increased during development and adult age. Lipid peroxidation was increased at birth on most structures, and the effect was abolished thereafter. In the prefrontal cortex, lipid peroxidation was unaltered at birth and diminished thereafter, while protein oxidation was increased on PND0 and decreased on PND60. Protein oxidation was also decreased in the cerebellum at adult age. Our results shown controlled gestational CR to improve antioxidant defenses and protect offspring's brain from oxidative stress, especially in adulthood, as a result of developmental metabolic programming.

Adaptative response to enhanced basal oxidative damage in sod mutants from Saccharomyces cerevisiae.

We investigated the adaptative response of S. cerevisiae in sod mutants (sod 1 Delta, sod 2 Delta and sod 1 Deltasod 2 Delta) after H(2)O(2) treatment in the stationary phase. sod 2 Delta and sod 1 Deltasod 2 Delta demonstrated the highest levels of GSH in the control, suggesting that pathways which include GSH protect these double mutants against oxidative stress. In addition, sod 1 Delta and sod 1 Deltasod 2 Delta had higher iron levels than the wild-type, independently of H(2)O(2) stress. Fe levels were increased in sod 2 Delta following H(2)O(2) In addition, the sod 2 Delta mutant was more sensitive to H(2)O(2) treatment than the wild-type. These results suggest that sod 2 Delta sensibility may be associated with *OH production by the Fenton reaction. This increased iron demand in the sod 2 Delta mutant may be a reflection of the cells' efforts to reconstitute proteins that are inactivated in conditions of excess superoxide. MDA levels were assayed by HPLC in these mutants. The highest MDA levels could be observed after 10mM H(2)O(2) treatment in the sod 1 Deltasod 2 Delta double mutant. After treatment with a GSH inhibitor, the MDA level was still higher in the same strain. Thus, both direct and indirect GSH pathways are involved in the protection of lipid membranes and proteins in these mutants and may constitute an adaptative response to enhanced basal oxidative damage produced by superoxide.

High levels of catalase in sod mutants of Saccharomyces cerevisiae in high aeration conditions

Saccharomyces cerevisiae mutants deficient in superoxide dismutase genes (sod1delta, sod2delta and sod1deltasod2delta mutants) in a stationary phase of growth under high aeration conditions were subjected to H2O2 stress. All the mutants were sensitive after H2O2 treatment. Glutathione peroxidase levels were significantly lower in sod1delta and sod2delta single mutants than in the wild-type without treatment. After exposure to H2O2 concentrations, glutathione peroxidase levels were increased in sod1deltasod2delta double mutants and the sod2delta single mutant, while sod1delta maintained lower gluthatione peroxidase activities. The sod2delta mutant demonstrated a similar catalase activity to that of the wild-type without treatment, whilst decreased catalase activity was observed in conditions of low aeration. Untreated sod1deltasod2delta double mutant cells presented a lower catalase activity. Catalase levels were higher under high aeration conditions than under microaerophilic conditions, including in sod1deltasod2delta cells that contain less H2O2, since SOD catalyzes the cleavage of superoxide producing H2O2 and oxygen. We suggest that catalase is not essential for sod mutants under normal conditions, but plays an important role in the acquisition of tolerance to oxidative stress induced by high aeration

Saccharomyces cerevisiae deficientes nos genes da superóxido dismutase (mutantes sod1delta, sod2deltae sod1deltasod2delta) cultivados em fase estacionária sob condições de alta aeração foram submetidos ao estresse com peróxido de hidrogênio (H2O2). Todos os mutantes mostraram-se sensíveis após o tratamento com o H2O2. A enzima glutationa peroxidase (GPx) apresentou níveis significativamente mais baixos nos simples mutantes sod1D e sod2delta que na cepa selvagem sem tratamento. Após, a exposição a diferentes concentrações de H2O2, os níveis da glutationa peroxidase aumentaram no duplo mutante sod1deltasod2delta e no simples mutante sod2delta, enquanto o mutante sod1delta manteve baixa atividade da glutationa peroxidase. O mutante sod2delta demonstrou atividade da catalase similar a da cepa selvagem sem tratamento, enquanto foi observado que a atividade da catalase decresceu em condições de baixa aeração. O duplo mutante sod1deltasod2delta apresentou baixa atividade da catalase mesmo sem tratamento. Os níveis da catalase foram maiores em condições de alta aeração do que em condições microaerófilas, inclusive o duplo mutante sod1deltasod2delta contém menos H2O2, visto que, a SOD catalisa a clivagem do superóxido produzindo H2O2 e oxigênio. Nós sugerimos neste trabalho que a catalase não é essencial para os mutantes sod sob condições normais, mas ela participa de uma importante via na aquisição da tolerância ao estresse oxidativo induzido por condições de alta aeração.