Differential protein expression due to Se deficiency and Se toxicity in rat liver.

There is a U-shaped dose-response between selenium (Se) status and health outcomes, but underlying metabolic processes are unclear. This study aims to identify candidate proteins in liver regulated by dietary Se, ranging from deficiency to toxic. Male rats (n=4) were fed graded Se concentrations as selenite for 28 days. Bulk Se analysis was performed by ICP-MS on both soluble and insoluble fractions. Soluble fraction samples were chromatographically separated for identification of selenocompounds by SEC-ICP-MS and protein quantification by LC-MS/MS. Bioinformatics analysis compared low-Se (0 and 0.08 µg Se g-1) and high-Se (0.8, 2 and 5 µg Se g-1) with adequate-Se (0.24 µg Se g-1) diets. Major breakpoints for Se were seen at 0.8 and 2 µg Se g-1 in the insoluble and soluble fractions, respectively. Glutathione peroxidase 1 protein abundance reached a plateau at ≥0.08 µg Se g-1diet; Se bound to selenium binding protein 2 was observed with 2 and 5 µg Se g-1 Se. The extreme diets presented the highest number of differentially expressed (P value <0.05, FC ≥1.2) proteins in comparison to the adequate-Se diet (0 µg Se g-1: 45 proteins; 5 µg Se g-1: 59 proteins); 13 proteins were commonly affected in 0 and 5 µg Se g-1 treatments. Network analysis revealed that the metabolism of glutathione, xenobiotics and amino acids were enriched in both 0 and 5 µg Se g-1 diets, indicating a U-shape effect of Se. This similarity is likely due to down-stream effects of lack of essential selenoproteins in Se deficiency and due to toxic effects of Se that exceeds the capacity to cope with excess Se.

Neurological effects of iron supplementation in infancy: finding the balance between health and harm in iron-replete infants.

Iron mediates many biochemical processes in neural networks that proliferate during brain development. Insufficient iron causes irreversible neurodevelopmental deficits, and most high-income countries recommend that infants older than 4-6 months receive additional iron via food fortification or supplementation to prevent iron-deficiency anaemia. Now that the prevalence of iron-deficiency anaemia in children has decreased to less than 10% in most developed countries, concerns that the recommended intakes far exceed those required to prevent iron-deficiency anaemia have been raised, and emerging evidence suggests that iron overexposure could be linked to adverse outcomes later in life. In this Viewpoint, we discuss the importance of iron for neurodevelopment, investigate the biochemical markers used to assess iron stores, summarise the disparity in public health policies among high-income countries, and discuss the potential association between iron overexposure and adverse neurological outcomes later in life. We present a case for new studies to establish the optimal amount of iron that both prevents deficiency and reduces the potential risk of long-term negative health outcomes.

Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease.

Iron accumulates gradually in the ageing brain. In Parkinson's disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson's diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson's disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson's disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson's diseases and produce a potential biomarker of Parkinson's disease risk in preclinical individuals.

Selenium, selenoproteins and neurodegenerative diseases.

It is unsurprising that our understanding of the role of selenium in neurological function is somewhat immature, considering its relatively recent discovery as an essential element to human health. Selenocysteine, the 21st amino acid, is the defining feature of the 25 selenoprotein-encoding genes so far discovered within the human genome. The low abundance of these proteins in the brain belies the integral role they play in normal neurological function, from well-characterised antioxidant activity in the periphery to poorly understood mechanisms that modulate mitochondrial function and response to brain pathology. Selenium has been identified as playing a role in several neurodegenerative disorders, including Alzheimer's and Parkinson's disease, though its function as a 'cause or effect' of disease process remains unclear. This review discusses selenium metabolism in detail, specifically with regard to the role it plays within the central nervous system, and examines the most current literature investigating how selenium may be involved in chronic diseases of the central nervous system.

Selenium status and hair mercury levels in riverine children from Rondônia, Amazonia

Objective: Riverine communities in Rondônia State are exposed to high selenium (Se) content in their diet because of the high-selenium soils identified in the Amazon. However, the Amazonian population has a high mercury (Hg) exposure because this metal accumulates in the soil. Because children are more vulnerable to Hg toxicity, the aim of this study was to evaluate and correlate Se status and hair Hg levels in riverine children (aged 3–9 y) living in two different locations in Rondônia State: Demarcação area (DA) and Gleba do Rio Preto (GRP)...

Selenium status and hair mercury levels in riverine children from Rondônia, Amazonia.

OBJECTIVE: Riverine communities in Rondônia State are exposed to high selenium (Se) content in their diet because of the high-selenium soils identified in the Amazon. However, the Amazonian population has a high mercury (Hg) exposure because this metal accumulates in the soil. Because children are more vulnerable to Hg toxicity, the aim of this study was to evaluate and correlate Se status and hair Hg levels in riverine children (aged 3-9 y) living in two different locations in Rondônia State: Demarcação area (DA) and Gleba do Rio Preto (GRP). METHODS: Se levels were assessed using hydride generation quartz tube atomic absorption spectroscopy; total hair Hg levels were assessed using cold vapor atomic absorption spectrometry. Dietary intake was evaluated through a 24-h food record and a food frequency questionnaire. RESULTS: Forty-two children participated in this study. Eighty-four percent of the children from DA showed low plasma Se. Conversely, all children from GRP presented plasma Se levels above the reference values. Forty-five percent of the children from DA presented low erythrocyte levels, and 55% of the children from GRP showed concentration in erythrocyte above the reference values. The mean Se intake was 41.8 µg/d in DA and 179.0 µg/d in GRP. High hair Hg levels were observed in children from both the DA and GRP (3.57 ± 1.86 and 6.24 ± 5.89, respectively). CONCLUSIONS: Children from both riverine communities are likely to present altered Se status according to their dietary intake. Additionally, these children are highly exposed to Hg, mainly through fish consumption, and the toxicity of this metal may cause metabolic damage.

Efeitos do consumo de castanha-do-brasil ( Bertholetia excelsa H. B. K. ) sobre o estresse oxidativo em pacientes com comprometimento cognitivo leve e a relação com variações em genes de selenoproteínas / Effects of the intake of Brazil nut (Bertholetia excels H. B. K) on the oxidative stress in patients with mild cognitive impairment and its relation with polymorphisms in selenoprotein genes

Visto que o estresse oxidativo está intimamente relacionado com a progressão da demência, este se apresenta como um possível alvo terapêutico a fim de preservar as funções cognitivas. No mesmo sentido, estudos mostram o papel antioxidante do selênio, mineral que atua por meio das selenoproteínas, com destaque para a família de enzimas antioxidantes glutationa peroxidase (GPx) e a selenoproteína responsável pelo transporte de selênio, a selenoproteína P (SePP). Entretanto, diferentes genótipos dos genes que codificam essas selenoproteínas podem refletir em diferentes respostas diante de intervenções alimentares. Assim, este trabalho teve como objetivo verificar os efeitos da suplementação com castanha-do-brasil sobre o estresse oxidativo em pacientes com comprometimento cognitivo leve (CCL) e verificar sua relação com os polimorfismos rs1050450 (Pro198Leu) no gene da GPx1, rs3877899 e rs7579 no gene da selenoproteína P. Participaram do estudo 31 indivíduos com CCL, voluntários, de ambos os sexos, frequentadores do Ambulatório de Memória do Idoso do Serviço de Geriatria da Faculdade de Medicina da Universidade de São Paulo, com idade igual ou superior a 60 anos, que foram distribuídos aleatoriamente entre os grupos Castanha e Controle. O grupo Castanha recebeu uma unidade de castanha-do-brasil por dia durante seis meses. Foram avaliados os seguintes marcadores: determinação de selênio no plasma e nos eritrócitos, atividade da GPx eritrocitária, avaliação dos níveis de oxygen radical absorbance capacity (ORAC) e de malondialdeído (MDA) plasmáticos, perfil lipídico sérico e expressão gênica de GPx1 e SePP. Além disso, os participantes foram submetidos à avaliação cognitiva e genotipados quanto aos polimorfismos rs1050450, rs3877899 e rs7579. Cada unidade de castanha-do-brasil forneceu 288,75µg de selênio. Dentre os 31 participantes selecionados, apenas 20 concluíram o estudo, e observou-se que, antes da intervenção, os grupos de estudo não apresentavam diferença quanto aos níveis de selênio no plasma e no eritrócito, bem como na atividade da GPx e nos níveis plasmáticos de ORAC e de MDA. Porém, após a suplementação, verificou-se aumento significativo no selênio plasmático (290,6±74,6) e eritrocitário (574,6±181,4) e na atividade da GPx (59,55±20,79) no grupo Castanha, diferente do grupo Controle (47,48±11,7 no plasma; 33,5±16,1 no eritrócito; 42,54±13,05 atividade da GPx). Em relação ao MDA, verificou-se que ambos os grupos apresentaram aumento após a intervenção, porém não significativo. No caso do ORAC, não se verificou alteração entre os grupos após os seis meses. O escore CERAD, que avalia desempenho cognitivo, não foi diferente entre os grupos após o tratamento, entretanto as mudanças observadas na fluência verbal e na praxia construtiva ao longo do acompanhamento foram mais favoráveis no grupo Castanha. A frequência dos genótipos de referência foram 40% para Pro198Leu, 55% para rs7579 e 60% para rs3877899. Não foram identificadas diferenças entre os níveis de selênio, de atividade da GPx, de MDA e de ORAC entre os genótipos, porém em análise multivariada verificou-se que o alelo variante do Pro198Leu se relacionou com aumento de 0,613 dp na concentração de selênio no plasma no baseline. A influência dos polimorfismos na resposta à intervenção com castanha-do-brasil foi avaliada nos 11 participantes do grupo Castanha, e observou-se que os genótipos não influenciaram na resposta quanto os níveis de selênio plasmático e eritrocitário, bem como de MDA. Entretanto, quanto à atividade da GPx, embora todos os genótipos tenham apresentado aumento após a intervenção, isso não foi significativo para o genótipo dominante do rs7579 e para o variante do rs3877899. A expressão de GPx1 e de SePP também foi diferente entre os genótipos: indivíduos com alelo variante do Pro198Leu apresentaram redução da expressão da GPx1, enquanto carreadores do genótipo homozigoto dominante tiveram aumento. Também percebeu-se que a expressão da SePP foi reduzida em todos os genótipos, entretanto essa mudança foi mais relevante para os genótipos variantes do Pro198Leu e rs7579 e para o genótipo GG do rs3877899. A partir desses resultados, concluiu-se que o consumo de apenas uma castanha-do-brasil diariamente, durante seis meses, é suficiente para recuperar o estado nutricional relativo ao selênio, e isso parece ter efeitos positivos sobre a cognição em idosos com CCL. Além disso, observou-se que o polimorfismo Pro198Leu no gene da GPx1 parece influenciar o estado nutricional quanto ao selênio, bem como a expressão de GPx, enquanto que os polimorfismos rs7579 e rs3877899 parecem não influenciar, de maneira significativa, o metabolismo de selênio frente ao consumo de castanha-do-brasil

Since oxidative stress is closely related to progression of dementia, the antioxidant system may be a potential therapeutic target to preserve cognitive function. In this way, studies show the antioxidant role of selenium, which plays as selenoproteins especially glutathione peroxidase (GPx) family and selenoprotein P (SePP). However, different genotypes of selenoprotein genes may result in different response to dietary intake. Therefore, this work aimed to verify the effects of Brazil nuts intake on oxidative stress and the role of the polymorphisms rs1050450 (Pro198Leu) in GPx1 gene and rs7579 and rs3877899 in SePP gene in mild cognitive impairment (MCI) patients. Study subjects comprised 31 voluntary patients with MCI who attended the Memory and Aging Unit of the Geriatrics Division, University of São Paulo Medical School (Brazil). They were randomly assigned to ingestion of Brazil nuts or to the control group. Brazil nuts group received one nut daily during six months. The following parameters were analysed: selenium concentration in plasma and erythrocyte, GPx activity in erythrocyte, plasmatic levels of oxygen radical absorbance capacity (ORAC) and of malondialdedyde (MDA), serum lipid profile. Besides, we evaluated cognitive performance and the patients were genotyped to rs1050450, rs3877899 e rs7579 polymorphisms. Each Brazil nut provided 288.75µg of selenium. Among 31 enrolled participants, only 20 finished the study. No differences regarding selenium levels, GPx activity, ORAC and MDA levels were observed at baseline between groups. However, after treatment, we observed significant increase in selenium in plasma (290.6±74.6) and in erythrocyte (574.6±181.4) and in GPx activity (59.55±20.79) in treated group, unlike control group (47.48±11.70 selenium in plasma; 33.5±16.1 selenium in erythrocyte; 42.54±13.05 GPx activity). Although not significant, MDA level increased after 6 months in both groups and ORAC levels were not different across time. CERAD total score was not different across time between groups, however changes in verbal fluency and constructional praxis subtests across time were significantly more favorable on the supplemented group when compared with control group. The frequency of dominant genotypes for Pro198Leu, rs7579 and rs3877899 were 40%, 55% and 60%, respectively. We did not observe differences regarding to selenium ORAC and MDA levels and GPx activity among genotypes, however after linear regression analysis the presence of variant allele of Pro198Leu was associated with an increase of 0.613 SD in selenium plasma level at baseline. The effect of polymorphisms in response to Brazil nut intake was analysed in Brazil nut group, and we observed that sele nium and MDA levels were not affected by polymorphisms. However although GPx activity increased in all genotype groups, this was not significant in dominant genotype of rs7579 and variant genotypes of rs3877899. GPx1 and SePP expression was also different among groups across time: variant allele of Pro198Leu presented decreased expression of GPx1 while dominant homozygous presented increase of expression. We also observed that SePP expression was reduced in all genotypes, but his was more important in variant genotypes of Pro198Leu and rs7579 and in GG genotype of rs3877899. From these results, we can conclude that consumption of only one Brazil nut is enough to restore selenium status, and this may be positive effects on cognition performance. Furthermore we observed that Pro198Leu polymorphism may influence selenium nutritional status and GPx activity whereas rs7579 and rs3877899 polymorphisms did not have an effect on selenium metabolism after Brazil nut intake

Importance and management of micronutrient deficiencies in patients with Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia, and it generally affects the elderly. It has been suggested that diet is an intensively modifiable lifestyle factor that might reduce the risk of AD. Because epidemiological studies generally report the potential neuronal protective effects of various micronutrients, the aim of this study was to perform a literature review on the major nutrients that are related to AD, including selenium, vitamins C and E, transition metals, vitamin D, B-complex vitamins, and omega-3 fatty acids.

Glutathione peroxidase 1 Pro198Leu polymorphism in Brazilian Alzheimer's disease patients: relations to the enzyme activity and to selenium status.

BACKGROUND/AIMS: Oxidative stress plays a central role in Alzheimer's disease (AD). Pro198Leu cytosolic glutathione peroxidase (GPx1) polymorphism seems to be associated with a lower activity of this enzyme, but there are no studies with AD patients. Thus, the aim was to determine the frequency of the GPx1 Pro198Leu polymorphism in AD patients and to verify its relation to glutathione peroxidase (GPx) activity and selenium (Se) status. METHODS: The study was carried out in a group of AD elderly (n = 28) compared to a control group (n = 29). Blood Se concentrations were measured through hydride generation atomic absorption spectroscopy. GPx activity was determined using a commercial kit, and the polymorphism using amplified DNA sequencing. RESULTS: The distribution of genotypes was not different between groups. The variant allele frequency was 0.179 (AD group) and 0.207 (control group). Although no differences regarding GPx activity were found between individuals with different genotypes, lower blood Se levels were found in Pro/Pro AD patients compared to Pro/Pro control subjects, which was not found in the Pro/Leu groups. Moreover, the association between the erythrocyte Se concentration and GPx activity was affected by the Pro198Leu genotype. CONCLUSIONS: Results indicate that this polymorphism had apparently affected Se status in AD patients and that more studies in this field are necessary.

Nutritional status of selenium in Alzheimer's disease patients.

Studies have shown that various antioxidants are decreased in different age-related degenerative diseases and thus, oxidative stress would have a central role in the pathogenesis of many disorders that involve neuronal degeneration, including Alzheimer's disease (AD). The present study aimed to assess the nutritional status of Se in AD patients and to compare with control subjects with normal cognitive function. The case-control study was carried out on a group of elderly with AD (n 28) and compared with a control group (n 29), both aged between 60 and 89 years. Se intake was evaluated by using a 3-d dietary food record. Se was evaluated in plasma, erythrocytes and nails by using the method of hydride generation atomic absorption spectroscopy. Deficient Se intake was largely observed in the AD group. AD patients showed significantly lower Se levels in plasma, erythrocytes and nails (32.59 microg/l, 43.74 microg/l and 0.302 microg/g) when compared with the control group (50.99 microg/l, 79.16 microg/l and 0.400 microg/g). The results allowed us to suggest that AD has an important relation with Se deficiency.

Estresse oxidativo na Doença de Alzheimer: o papel das vitaminas C e E / Oxidative stress in Alzheimer?s disease: the role of vitamins C and E

Alzheimer's disease is becoming a big public health problem in the world. Previous studies have shown that oxidant-induced changes occur in the cerebral tissue in Alzheimer's disease and, in this context, some observational studies have suggested that antioxidant supplements, including vitamins C and E, or a diet with high intake of antioxidants prevent oxidative stress that possibly causes neuronal loss in Alzheimer's disease, and thus can reduce the risk of developing Alzheimer's disease. In this context, the aim of this work was to review some original studies which relate the role of vitamins C and E to the prevention of Alzheimer's disease.

La enfermedad de Alzheimer se ha transformado en un problema de salud pública mundial. Algunos estudios muestran que cambios en el cerebro de portadores son provocados por el estrés oxidativo. En este sentido, algunos estudios observacionales sugieren que la suplementación con antioxidantes, incluidas las vitaminas C y E, o una dieta rica en estos nutrientes puede prevenir el estrés oxidativo que posiblemente provoca la perdida neuronal observada en la enfermedad de Alzheimer, disminuyendo el riesgo de ocurrencia de la enfermedad. El objetivo del trabajo fue revisar algunas informaciones actualizadas sobre el papel de las vitaminas C y E en la prevención de la enfermedad de Alzheimer.

A Doença de Alzheimer está se tornando um grande problema de saúde pública no mundo. Pesquisas mostram que o estresse oxidativo gera mudanças no cérebro de portadores de Doença de Alzheimer e, nesse contexto, alguns estudos observacionais têm sugerido que a suplementação de antioxidantes, incluindo as vitaminas C e E, ou uma dieta rica nesses nutrientes podem prevenir o estresse oxidativo que possivelmente causa a perda neuronal observada na Doença de Alzheimer, diminuindo assim, o risco para a doença. Nesse sentido, o objetivo deste trabalho foi revisar alguns artigos originais que relacionam o papel das vitaminas C e E na diminuição do risco da Doença de Alzheimer.

Ciclo menstrual e consumo de alimentos / Menstrual cycle and food consumption / Ciclo menstrual y el consumo de alimentos

Objetivou-se neste trabalho, avaliar o consumo alimentar de mulheres durante as fases folicular e lútea do ciclo menstrual e estabelecer as possíveis relações entre a ingestão alimentar e os sintomas da Síndrome Pré-Menstrual. Foram investigadas 30 alunas dos cursos de Pós-Graduação da Universidade Federal de Santa Catarina, por meio de registro alimentar de três dias, sendo um de final de semana, durante as fases folicular e lútea. Na lútea, aplicou-se um questionário de sintomas pré-menstruais. Os dados foram avaliados no programa SPSS 14 for Windows. O consumo energético, de carboidratos e lipídios, foi significativamente maior na fase lútea (p<0,0001). Os sintomas da Síndrome Pré-Menstrual ocorreram em 96,7% da amostra investigada, sendo que 63,4% apresentaram manifestação severa e 3,3% leve. Os sintomas emocionais foram os mais citados pela amostra (93,3%). O apetite foi maior na fase pré-menstrual em 53,3% das participantes e 43,3% relataram ter vontade de comer alimentos doces neste período. Não foram encontradas correlações entre o consumo alimentar (energético e de macronutrientes) e a manifestação de sintomas. A partir destes resultados, acredita-se que exista interferência do ciclo ovariano sobre o comportamento alimentar. Assim, sugere-se a realização de pesquisas com maior amostragem, a fim de verificar a estreita relação entre o consumo alimentar e a manifestação de sintomas da Síndrome Pré-Menstrual.

The objective of this study was to evaluate the dietary intake of women during the follicular and luteal phases of the menstrual cycle and establish the possible relationship between food intake and symptoms of Premenstrual Syndrome. We investigated 30 female students of graduate courses at the Federal University of Santa Catarina, through three days of food records, one weekend during the follicular and luteal phases. In the luteal, applied a questionnaire to premenstrual symptoms. The data were analyzed using SPSS 14 for Windows. The energy consumption of carbohydrates and lipids, was significantly higher in the luteal phase (p <0.0001). The symptoms of premenstrual syndrome occurred in 96.7% of the investigated sample, and 63.4% had severe outbreak and 3.3% mild. The emotional symptoms were the most cited by the sample (93.3%). The appetite was higher in the premenstrual phase in 53.3% and 43.3% of participants reported having cravings for sweet foods in this period. No correlation was found between dietary intake (energy and nutrients) and the manifestation of symptoms. From these results, we believe that there is interference of the ovarian cycle on feeding behavior. Thus, it is suggested to conduct research using larger samples to verify the close relationship between food consumption and manifestation of symptoms of premenstrual syndrome.

El objetivo de este estudio fue evaluar la ingesta alimentaria de las mujeres durante las fases folicular y lútea del ciclo menstrual y establecer la posible relación entre la ingesta de alimentos y los síntomas del Síndrome Premenstrual. Se investigaron 30 alumnas de los cursos de postgrado en la Universidad Federal de Santa Catarina, a través de tres días a partir de los registros de alimentos, un fin de semana durante las fases folicular y luteínica. En la fase lútea, aplicó un cuestionario a los síntomas premenstruales. Los datos fueron analizados utilizando el programa SPSS 14 para Windows. El consumo de energía de los carbohidratos y lípidos, fue significativamente mayor en la fase lútea (p <0,0001). Los síntomas del síndrome premenstrual se produjo en el 96,7% de la muestra investigada, y 63.4% tenían brote severo y el 3,3% leve. Los síntomas emocionales son los más citados por los encuestados (93,3%). El apetito es mayor en la fase premenstrual en el 53,3% y 43,3% de los participantes reportó haber antojos por alimentos dulces en este período. No se encontró correlación entre el consumo de la dieta (energía y nutrientes) y la manifestación de los síntomas. A partir de estos resultados, creemos que hay interferencia del ciclo ovárico en la conducta alimentaria. Por lo tanto, se sugiere llevar a cabo la investigación con muestras más grandes para comprobar la estrecha relación entre el consumo de alimentos y la manifestación de los síntomas del síndrome premenstrual.