Efeito da restrição calórica durante o período gestacional sobre parâmetros bioquímicos mitocondriais e comportamentais na prole de ratos

Alterações no ambiente intrauterino podem levar a consequências que perduram por toda a vida, algumas estão ligadas ao estresse oxidativo e à função mitocondrial, e podem afetar o desenvolvimento físico e motor dos filhotes, além do comportamento alimentar. Nesse contexto, o sobrepeso na gestação é uma preocupação crescente, que pode aumentar o risco de desenvolvimento de doenças crônicas não transmissíveis na vida adulta. Nesse sentido, a restrição calórica (RC) pode exercer um efeito protetor, se bem controlada, já que a desnutrição na gestação também causa efeitos indesejados. Para avaliar o efeito da RC gestacional, dividimos as ratas grávidas entre os grupos controle e RC. O segundo recebeu 20% menos ração, e o consumo de micronutrientes foi equalizado via gavagem. Cerebelo, córtex pré-frontal, hipocampo e hipotálamo dos filhotes foram avaliados nos dias pósnatais (DPN) 0, 7, 21 e 60. A prole também foi submetida a testes comportamentais aos 21 e 60 dias. Observamos um aumento no conteúdo de oxidantes ao nascimento nas regiões encefálicas avaliadas, exceto no cerebelo. Esse efeito foi praticamente abolido nas idades posteriores. As atividades das enzimas antioxidantes estavam, em sua maioria, diminuídas no DPN0, com algumas enzimas ativadas. No DPN7, as enzimas cujas atividades estavam diminuídas passaram a estar inalteradas, e muitas das que não se alteraram ao nascimento estavam ativadas. No DPN60, muitas enzimas foram ativadas, especialmente no córtex pré-frontal e hipocampo. O conteúdo de glutationa reduzida (GSH) diminuiu em três estruturas avaliadas ao nascimento e aumentou no cerebelo e hipotálamo durante o desenvolvimento e no córtex pré-frontal na idade adulta. Os níveis de vitamina C diminuíram nas primeiras idades e aumentaram nas idades posteriores. A lipoperoxidação aumentou no nascimento na maioria das estruturas, e o efeito foi abolido nas idades subsequentes. No córtex pré-frontal, a peroxidação lipídica diminuiu em DPN7, 21 e 60. A oxidação proteica aumentou em DPN0 e diminuiu em DPN60 nessa estrutura. A oxidação proteica também diminuiu no cerebelo na idade adulta. A função mitocondrial, assim como o conteúdo de superóxido, estava diminuída na maioria das estruturas no DPN0, e adaptou-se nas idades posteriores. Na idade adulta a função mitocondrial estava aumentada e o conteúdo de superóxido inalterado ou diminuído. Os complexos do sistema de transporte de elétrons (STEM) apresentaram atividade diminuída em DPN0 e aumentada na idade adulta no cerebelo. A RC não atrasou o desenvolvimento físico e motor dos filhotes e influenciou positivamente no comportamento alimentar dos mesmos na idade adulta. Nossos resultados demonstram que uma RC bem controlada no período gestacional pode melhorar a homeostase redox e a atividade mitocondrial no encéfalo, especialmente na idade adulta, sem promover desnutrição, ao menos em modelo animal em nossas condições experimentais.Alterations in the intrauterine environment can lead to lifelong consequences, some of them are related to oxidative stress and mitochondrial dysfunction and can affect physical and motor development of the pups. Feeding behavior may also be affected. In this context, maternal overweight demands attention, since disease development in adult life may be increased by this condition. In this sense, caloric restriction (CR) may have protective effect if well controlled avoiding maternal undernutrition. In order to evaluate CR effects, we divided pregnant rats into control and CR groups. The second received 20% less chow, and micronutrients consumption was equalized via gavage. Cerebellum, prefrontal cortex, hippocampus, and hypothalamus were evaluated on offspring’s postnatal days (PND) 0, 7, 21, and 60. Animals were also submitted to behavioral tests on PND21 and 60. We observed increased oxidant levels in all brain regions evaluated, except for the cerebellum on PND0. This effect was abolished on latter ages. Antioxidant enzyme activities were mostly decreased on PND0. On PND7, affected enzymes were either equal to control or presented increased activity. On PND60, most enzymes were activated, especially in the prefrontal cortex and hippocampus. Reduced glutathione (GSH) levels were decreased in three brain regions evaluated at birth, increased in the cerebellum and hypothalamus during development and in the prefrontal cortex at adult age. Vitamin C levels decreased in the first ages and were increased in the latter ones. Concerning to oxidative markers, lipid peroxidation was increased at birth in most regions and the effect was abolished thereafter. In the prefrontal cortex, lipid peroxidation was decreased on PND7, 21 and 60. Protein oxidation was increased on PND0 and decreased on PND60 in this region. In the cerebellum, protein oxidation was also decreased at adult age. Mitochondrial function, as well as the mitochondrial superoxide content, was decreased in most structures on PND0 and went through adaptation. At adult age, mitochondrial function was increased and superoxide levels were either unaltered or decreased. Mitochondrial electron transport system (METS) complexes showed decreased activity on PND0 and were activated on PND60 in the cerebellum. CR did not delay physical or neuromotor development and positively influenced pups’ feeding behavior at adult age. Our results show that maternal CR, if well controlled, may improve redox homeostasis and mitochondrial function in the offspring’s brain, especially at adult age, without promoting undernutrition, at least at our experimental conditions

Supplementation with green tea and oregano extracts on productive characteristics, blood metabolites, and antioxidant status of Jersey cows during the transition period

Plant extracts have been recognized as beneficial to human health and have been evaluated as feed additive for domestic and companion animals. This study evaluated oregano and green tea extracts fed to Jersey cows from approximately 21 d before calving to 21 d after calving on milk production, milk composition, and blood metabolites as well as investigated immunological and antioxidant attributes. Twenty-four Jersey cows with 441±27 kg of BW, 3.5±0.3 of body condition score (BCS), and 2.7±1.8 lactations were selected at approximately 28d before the expected parturition date and were randomly assigned to three treatments with eight cows each: without plant extracts in diet (control – CON), addition of 10g per day of oregano extract (OR), and addition of 5g per day of green tea extract (GT). Feed intake, BW, BCS, blood metabolites, hemogram as well as oxidative stress biomarkers were evaluated from approximately 3 weeks prepartum to 3 weeks postpartum (transition period) while milk production and composition were evaluated during the first 3 weeks of lactation. Plant extracts did not change BW, BCS, and DM intake (DMI) throughout the transition period, but OR increased in approximately 20% total digestive nutrients and metabolizable energy intake on days 15 and 16 postpartum compared with CON. In the prepartum, OR increased in 48% platelets count compared to the CON, while GT augmented in 142% eosinophils compared with CON. Oregano extract reduced the levels of reactive species in the erythrocytes in 40% during prepartum and postpartum compared with CON, while GT reduced its levels in 24 and 29% during prepartum and postpartum, respectively, when compared with CON. In the postpartum period, OR increased in 60% the carbonylated protein content compared with CON, while GT reduced in 45% the levels of reactive species in plasma compared with CON. During the postpartum, both extracts increased in 33% the concentration of reduced glutathione when compared with CON. Moreover, GT tended to decrease feed efficiency in 11% when compared with CON; OE reduced milk pH and somatic cell count when compared with CON. In conclusion, OE and GT did not expressively affect immunological attributes in blood but reduce some oxidative stress biomarkers without compromising productive traits of Jersey cows during the transition period

A restrição calórica intrauterina altera o status antioxidante em encéfalo de ratos

A restrição calórica é considerada um fator de intervenção ideal na promoção da saúde. Diversos autores demonstraram sua capacidade de aumentar a expectativa de vida e proteger diversos organismos de uma série de doenças, inclusive as que estão relacionadas com o aumento do estresse oxidativo. Intervenções no período gestacional induzem uma reprogramação metabólica nos descendentes, podendo alterar o risco de desenvolver doenças crônicas na vida adulta. Nosso objetivo nesse trabalho foi avaliar os efeitos da restrição calórica materna de 40% durante o período gestacional sobre a produção de espécies reativas, modulação das defesas antioxidantes enzimáticas e não enzimáticas e parâmetros de dano oxidativo no cerebelo e córtex cerebral total de ratas mães e seus filhotes. Uma diminuição na concentração de espécies reativas no cerebelo de mães e filhotes foi encontrada, bem como, uma diminuição nos níveis de superóxido mitocondrial no cerebelo dos filhotes. Por outro lado, o córtex cerebral dos filhotes apresentou uma redução nos níveis de superóxido mitocondrial e um aumento na concentração de óxido nítrico. Foi encontrada uma diminuição da capacidade antioxidante enzimática e não enzimática dos filhotes, onde a superóxido-dismutase apresentou atividade aumentada; enquanto a catalase, a glutationa-peroxidase e a glutarredoxina foram negativamente afetadas. As ratas prenhes também apresentaram diminuição da capacidade antioxidante enzimática, entretanto, de maneira mais sutil. As defesas antioxidantes não enzimáticas não sofreram alterações no córtex das mães, enquanto que no cerebelo, demonstraram um padrão adaptativo. Apesar disso, parâmetros de dano oxidativo não sofreram alterações. Nossos resultados são um ponto de partida para esclarecer o impacto da má nutrição na vida intrauterina sobre parâmetros de estresse oxidativo. Acreditamos que a restrição calórica durante a gestação aumenta a vulnerabilidade de ratas prenhes e seus filhotes a futuros danos oxidativos. Entretanto, mais estudos são necessários para explicar por quais mecanismos a restrição calórica afeta as defesas antioxidantes.Caloric restriction has been considered the cornerstone of health, considering its capacity of increasing life span and protecting distinct organisms against a series of diseases, among which, those related to oxidative stress. Interferences in the maternal environment are known to reprogram the offspring metabolism response, impacting in the risk of chronic diseases development in adulthood. Our aim was to assess the effect of 40% caloric restriction on reactive species levels, enzymatic and non-enzymatic antioxidant defenses, besides the oxidative damage parameters in the cerebellum and the total cerebral cortex of pregnant rats and their offspring. Both dams and pups showed an intense oxidative modulation caused by caloric restriction in the cerebellum and cerebral cortex. Dichlorofluorescein oxidation was reduced in the cerebellum of calorie restricted dams and their offspring, while the cerebral cortex was not affected. Decreased mitochondrial superoxide levels were found in the cerebellum and cerebral cortex of pups, while nitric oxide was increased in cortex. Considering that reactive oxygen species were probably altered in brain of diet restricted rats, we measured the activities of the most important antioxidant enzymes responsible by its elimination. In a comprehensive way, superoxide dismutase activity was increased in the cerebellum of dams and in both structures of pups, while it was decreased on dams’ cerebral cortex. Both brain structures were strongly affected concerning to catalase, glutathione peroxidase, and glutaredoxin activities, which were decreased in pups and their mothers. Furthermore, non-enzymatic defenses were significantly decreased in pups, despite the fact that dams showed an adaptive pattern in the cerebellum and no alteration in the cerebral cortex. Even though the results suggest increased oxidative status, lipids and proteins were not oxidatively affected. Our data clarify, at least in oxidative aspects, the effects of poor nutrition on brain metabolism in critical periods of life: fetal development and pregnancy. In view of our results, we believe that caloric restriction during pregnancy increases the susceptibility of dams and their offspring to a future oxidative aggression

Polyols accumulated in ribose-5-phosphate isomerase deficiency increase mitochondrial superoxide production and improve antioxidant defenses in rats’ prefrontal cortex

The ribose-5-phosphate isomerase deficiency is an inherited condition, which results in cerebral d-arabitol and ribitol accumulation. Patients present leukoencephalopathy, mental retardation, and psychomotor impairment. Considering that the pathophysiology of this disorder is still unclear, and literature are sparse and contradictory, reporting pro and antioxidant activities of polyols, the main objective of this study was to investigate some parameters of oxidative homeostasis of prefrontal cortex of rats incubated with d-arabitol and ribitol. We found evidences that ribitol promoted an increase in antioxidant enzymes activity (superoxide dismutase, catalase, and glutathione peroxidase), probably secondary to enhanced production of superoxide radical, measured by flow cytometry. Oxidation of proteins and lipids was not induced by polyols. Our data allow us to conclude that, at least in our methodological conditions, arabitol and ribitol probably have a secondary effect on the pathophysiology of ribose-5-phosphate isomerase deficiency

Quantitative trait locus affecting birth weight on bovine chromosome 5 in a F2 Gyr x Holstein population

Segregation between a genetic marker and a locus influencing a quantitative trait in a well delineated population is the basis for success in mapping quantitative trait loci (QTL). To detect bovine chromosome 5 (BTA5) birth weight QTL we genotyped 294 F2 Gyr (Bos indicus) x Holstein (Bos taurus) crossbreed cattle for five microsatellite markers. A linkage map was constructed for the markers and an interval analysis for the presence of QTL was performed. The linkage map indicated differences in the order of two markers relative to the reference map (<A HREF="http://www.marc.usda.gov/">http://www.marc.usda.gov</A>). Interval analysis detected a QTL controlling birth weight (p < 0.01) at 69 centimorgans (cM) from the most centromeric marker with an effect of 0.32 phenotypic standard-error. These results support other studies with crossbred Bos taurus x Bos indicus populations