Vitamin A deficiency modulates iron metabolism independent of hemojuvelin (Hfe2) and bone morphogenetic protein 6 (Bmp6) transcript levels.

BACKGROUND: Considering that vitamin A deficiency modulates hepcidin expression and consequently affects iron metabolism, we evaluated the effect of vitamin A deficiency in the expression of genes involved in the hemojuvelin (HJV)-bone morphogenetic protein 6 (BMP6)-small mothers against decapentaplegic protein (SMAD) signaling pathway. METHODS: Male Wistar rats were treated: control AIN-93G diet (CT), vitamin A-deficient diet (VAD), iron-deficient diet (FeD), vitamin A- and iron-deficient diet (VAFeD), or 12 mg all-trans retinoic acid (atRA)/kg diet. RESULTS: Vitamin A deficiency (VAD) increased hepatic Bmp6 and Hfe2 mRNA levels and down-regulated hepatic Hamp, Smad7, Rarα, and intestinal Fpn1 mRNA levels compared with the control. The FeD rats showed lower hepatic Hamp, Bmp6, and Smad7 mRNA levels compared with those of the control, while in the VAFeD rats only Hamp and Smad7 mRNA levels were lower than those of the control. The VAFeD diet up-regulated intestinal Dmt1 mRNA levels in relation to those of the control. The replacement of retinyl ester by atRA did not restore hepatic Hamp mRNA levels; however, the hepatic Hfe2, Bmp6, and Smad7 mRNA levels were similar to the control. The atRA rats showed an increase of hepatic Rarα mRNA levels and a reduction of intestinal Dmt1 mRNA and Fpn1 levels compared with those of the control. CONCLUSIONS: The HJV-BMP6-SMAD signaling pathway that normally activates the expression of hepcidin in iron deficiency is impaired by vitamin A deficiency despite increased expression of liver Bmp6 and Hfe2 mRNA levels and decreased expression of Smad7 mRNA. This response may be associated to the systemic iron deficiency and spleen iron retention promoted by vitamin A deficiency.

Brazilian savanna fruits contain higher bioactive compounds content and higher antioxidant activity relative to the conventional red delicious apple.

The bioactive compounds content and the antioxidant activity (AA) of twelve fruits native to the Cerrado were compared with the Red Delicious apple by means of the antiradical efficiency (using the 2,2-diphenyl-1-picrylhydrazil assay/DPPH), ferric reducing antioxidant power (FRAP) and the ß-carotene/linoleic system. The antiradical efficiency (AE) and the kinetic parameters (Efficient concentration/EC50 and time needed to reach the steady state to EC50 concentration/TEC50) of the DPPH curve were also evaluated for comparison with the Trolox equivalent (TE) values. A strong, significant and positive correlation was observed between the TE and AE values, whereas a weak and negative correlation was observed between TE and EC50, suggesting that the values of AE and TE are more useful for the determination of antiradical activity in fruits than the widely used EC50. The total phenolic content found in the fruits corresponded positively to their antioxidant activity. The high content of bioactive compounds (flavanols, anthocyanins or vitamin C) relative to the apple values found in araticum, cagaita, cajuzinho, jurubeba, lobeira, magaba and tucum corresponded to the high antioxidant activity of these fruits. Flavanols and anthocyanins may be the main bioactive components in these Cerrado fruits. The daily consumption of at least seven of the twelve Cerrado fruits studied, particularly, araticum, cagaita, lobeira and tucum, may confer protection against oxidative stress, and thus, they may prevent chronic diseases and premature aging. The findings of this study should stimulate demand, consumption and cultivation of Cerrado fruits and result in sustainable development of the region where this biome dominates.

The association of markers of oxidative-inflammatory status with malnutrition in hemodialysis patients with serum ferritin lower than 500 ng/mL.

INTRODUCTION: Enhanced inflammatory-oxidative status is well established in chronic kidney disease. OBJECTIVE: The objective of this study was to evaluate the oxidative- inflammatory status and iron indices in patients undergoing maintenance hemodialysis (HD) with serum ferritin lower than 500 ng/mL, and to correlate them with nutritional status. METHOD: In a cross-sectional survey 35 HD patients (23 with normal nutritional status, 12 with Protein-Energy-Wasting syndrome, PEW), and healthy volunteers (n = 35) were studied. Serum concentration of iron, ferritin, transferrin saturation, malondialdehyde (MDA), protein carbonyl (PC), high-sensitive serum C -reactive protein (hs-CRP) and blood counts were determined. The nutritional status was determined by anthropometric and biochemical criteria. RESULTS: HD patients showed low values of hemoglobin and higher values of ferritin, MDA and PC when compared with healthy volunteers. HD subjects with PEW had higher values of PC and hs-PCR as compared to HD patients with normal nutritional status. A multiple logistic regression analysis showed that the independent variables PC (Wald Statistic 4.25, p = 0.039) and hs-CRP (Wald Statistic 4.83, p = 0.028) where related with the patients' nutritional condition. CONCLUSION: In HD patients with serum ferritin below 500 ng/mL was observed one association of the markers of oxidative stress and inflammation with poor nutritional status independently of serum ferritin, gender and age.

Dietary iron concentration may influence aging process by altering oxidative stress in tissues of adult rats.

Iron is an essential element. However, in its free form, iron participates in redox-reactions, leading to the production of free radicals that increase oxidative stress and the risk of damaging processes. Living organisms have an efficient mechanism that regulates iron absorption according to their iron content to protect against oxidative damage. The effects of restricted and enriched-iron diets on oxidative stress and aging biomarkers were investigated. Adult Wistar rats were fed diets containing 10, 35 or 350 mg/kg iron (adult restricted-iron, adult control-iron and adult enriched-iron groups, respectively) for 78 days. Rats aged two months were included as a young control group. Young control group showed higher hemoglobin and hematocrit values, lower levels of iron and lower levels of MDA or carbonyl in the major studied tissues than the adult control group. Restricted-iron diet reduced iron concentrations in skeletal muscle and oxidative damage in the majority of tissues and also increased weight loss. Enriched-iron diet increased hematocrit values, serum iron, gamma-glutamyl transferase, iron concentrations and oxidative stress in the majority of tissues. As expected, young rats showed higher mRNA levels of heart and hepatic L-Ferritin (Ftl) and kidneys SMP30 as well as lower mRNA levels of hepatic Hamp and interleukin-1 beta (Il1b) and also lower levels of liver protein ferritin. Restricted-iron adult rats showed an increase in heart Ftl mRNA and the enriched-iron adult rats showed an increase in liver nuclear factor erythroid derived 2 like 2 (Nfe2l2) and Il1b mRNAs and in gut divalent metal transporter-1 mRNA (Slc11a2) relative to the control adult group. These results suggest that iron supplementation in adult rats may accelerate aging process by increasing oxidative stress while iron restriction may retards it. However, iron restriction may also impair other physiological processes that are not associated with aging.

The association of markers of oxidative-inflammatory status with malnutrition in hemodialysis patients with serum ferritin lower than 500 ng/mL / Associação dos marcadores do estado oxidativo e inflamatório com a desnutrição em pacientes hemodialisados com ferritina menor do que 500 ng/mL

INTRODUCTION: Enhanced inflammatory-oxidative status is well established in chronic kidney disease. OBJECTIVE: The objective of this study was to evaluate the oxidative- inflammatory status and iron indices in patients undergoing maintenance hemodialysis (HD) with serum ferritin lower than 500ng/mL, and to correlate them with nutritional status. METHOD: In a cross-sectional survey 35 HD patients (23 with normal nutritional status, 12 with Protein-Energy-Wasting syndrome, PEW), and healthy volunteers (n = 35) were studied. Serum concentration of iron, ferritin, transferrin saturation, malondialdehyde (MDA), protein carbonyl (PC), high-sensitive serum C -reactive protein (hs-CRP) and blood counts were determined. The nutritional status was determined by anthropometric and biochemical criteria. RESULTS: HD patients showed low values of hemoglobin and higher values of ferritin, MDA and PC when compared with healthy volunteers. HD subjects with PEW had higher values of PC and hs-PCR as compared to HD patients with normal nutritional status. A multiple logistic regression analysis showed that the independent variables PC (Wald Statistic 4.25, p = 0.039) and hs-CRP (Wald Statistic 4.83, p = 0.028) where related with the patients' nutritional condition. CONCLUSION: In HD patients with serum ferritin below 500 ng/mL was observed one association of the markers of oxidative stress and inflammation with poor nutritional status independently of serum ferritin, gender and age.

INTRODUÇÃO: Na doença renal crônica, a presença de um estado inflamatório-oxidativo aumentado está bem estabelecida. OBJETIVO: O objetivo do presente estudo foi avaliar o estado oxidativo e inflamatório e o perfil do ferro em pacientes submetidos à hemodiálise crônica de manutenção, com ferritina menor do que 500 ng/mL, e correlacioná-los com o estado nutricional. MÉTODO: Em estudo transversal, em 35 pacientes sob hemodiálise (23 com estado nutricional normal, 12 com desnutrição energético-proteica (DEP) e 35 voluntários sadios foram determinados os índices hematimétricos e as concentrações séricas do ferro, da ferritina e avaliada a saturação de transferrina. O estado oxidativo foi determinado por meio das concentrações séricas do malondialdeído (MDA) e da proteína carbonil (PC). Nos indivíduos sob hemodiálise o estado inflamatório foi avaliado por meio da proteína C reativa ultrassensível determinada no soro (hs-PCR). O estado nutricional foi determinado por critérios antropométricos e bioquímicos. RESULTADOS: Os pacientes da hemodiálise mostraram anemia e um estado oxidativo mais elevado do que os voluntários sadios. Os pacientes hemodialisados com DPE mostraram ferritina e um estado inflamatório-oxidativo mais elevado se comparados aos com boa condição nutricional. Em análise de regressão logística múltipla, os níveis séricos de PC e hs-CRP foram correlacionados com o estado nutricional. PC (Estatística Wald 4.25, p = 0,039), CRP (Estatística Wald 4.83, p = 0,028). CONCLUSÃO: Em indivíduos submetidos à hemodiálise, com ferritina menor do que 500 ng/mL. Observou-se uma associação entre os marcadores de estresse oxidativo e inflamatório com o estado nutricional, independentemente da idade, gênero e dos índices do ferro.

Vitamin A deficiency increases hepcidin expression and oxidative stress in rat.

OBJECTIVE: The interaction between vitamin A and iron status has been widely reported; however, the exact mechanism involved in this interaction has not been well characterized. The present study investigated the mechanism involved in tissue iron accumulation and changes in the oxidative status in vitamin A-deficient rats. METHODS: Rats were treated with a control diet, a vitamin A-deficient diet, or a vitamin A/iron-deficient diet for 57 d. The animals were sacrificed; the blood, liver, and spleen were collected for biochemical analysis. Analysis of variance or Mann-Whitney tests were used to compare groups and Pearson's or Spearman's tests to investigate the bivariate correlation. RESULTS: Vitamin A deficiency increased liver hepcidin mRNA and iron spleen concentrations; however, iron deficiency in vitamin A-deficient rats deeply inhibits liver hepcidin mRNA expression and significantly increases divalent metal transporter-1 mRNA levels. Liver ferroportin and hereditary hemochromatosis gene mRNA levels did not change in either treatment. In the vitamin A-deficient groups, liver carbonyl protein increased, whereas catalase and glutathione S-transferase activities decreased, suggesting that vitamin A protects the liver against protein oxidation. A significant positive correlation was found between lipid oxidative damage and iron concentration in the liver and spleen (r = 0.611, P = 0.007; r = 0.558, P = 0.025, respectively). CONCLUSION: These results suggest that vitamin A maintains iron homeostasis by the modulation of liver hepcidin expression. The increase of lipid peroxidation in vitamin A deficiency seems to be iron dependent, whereas protein oxidation is not.

Iron status and oxidative stress biomarkers in adults: a preliminary study.

OBJECTIVE: Although essential to many vital processes, iron catalyzes reactions that produce reactive oxygen species, which are associated with the increased risk of non-communicable chronic diseases and precocious aging. This study investigated whether ferritin, hemoglobin concentration, and dietary iron consumption are related to oxidative stress biomarkers in adults. METHODS: Data were collected from 134 allegedly healthy subjects >18 y of age who were randomly selected to participate in a cross-sectional study as part of the pilot project Prevalence of Risk Factors for Non-communicable Chronic Diseases in the Federal District, Brazil (VIVA Saúde-DF). Serum ferritin, malondialdehyde (MDA) and protein carbonyl concentrations, hemoglobin, and dietary iron consumption were analyzed. RESULTS: A weak positive correlation (r = 0.189, P = 0.032) and association (P = 0.046) was observed for serum ferritin and MDA. Hemoglobin concentrations were positively associated with serum MDA (P = 0.040). Dietary iron intake and serum protein carbonyl concentrations showed a weak positive correlation (r = 0.173, P = 0.046) for all subjects. Iron intake by women was positively associated with serum protein carbonyl (P = 0.03). A lower serum MDA concentration was found in ferritin-deficient subjects (P = 0.015) and men with anemia (P = 0.011). CONCLUSION: These results suggest that low levels of iron may reduce oxidative stress.

Biodisponibilidade de minerais em refeições vegetarianas e onívoras servidas em restaurante universitário / Mineral bioavailability in vegetarian and omnivorous meals served in a university restaurant

OBJETIVO: Avaliar a biodisponibilidade de cálcio, ferro e zinco nas dietas vegetarianas e onívoras, servidas no Restaurante Universitário da Universidade de Brasília. MÉTODOS: Foram coletadas três amostras de cada refeição, durante 5 dias, para determinação do conteúdo de fitato. O conteúdo em cálcio ferro e zinco foi estimado a partir de tabelas de composição de alimentos. A razão molar entre o ácido fítico e o mineral dietéticos foi utilizada como critério para avaliar a biodisponibilidade. RESULTADOS: As concentrações médias de ácido fítico, cálcio e ferro foram significantemente maiores na dieta vegetariana (p=0,0002; p=0,0015 e p=0,0227, respectivamente), enquanto a concentração de Zinco foi maior na dieta onívora (p=0,0205). Ambas as dietas apresentaram razões molares ácido fítico: cálcio e ácido fítico: ferro inferiores aos valores críticos (1,56 e 14, respectivamente), sugerindo que o fitato não deve comprometer a biodisponibilidade do cálcio ou do ferro nessas refeições. A razão molar ácido fítico: zinco, na dieta vegetariana, foi de 9,3 e na onívora de 4,9, caracterizando-as como refeições de média e alta biodisponibilidade para o zinco, respectivamente. O feijão e a soja eram os componentes dietéticos mais ricos em fitato nas duas refeições. CONCLUSÃO: Devido aos teores de cálcio e ferro nas duas refeições, a presença de fitato não deve representar risco de deficiência desses minerais para indivíduos que se alimentam diariamente no Restaurante Universitário da Universidade de Brasília. Entretanto, devido ao baixo teor de zinco nas refeições, a presença do fitato pode representar um risco de deficiência desse mineral, principalmente, para homens vegetarianos.

OBJECTIVE: To assess the bioavailability of calcium, iron and zinc in vegetarian and omnivorous meals served in the university restaurant of the Universidade de Brasília. METHODS: Three samples of each meal were collected during 5 days to determine the concentration of phytate. Calcium, iron and zinc contents were estimated by using food composition tables. The molar ratio between phytic acid and the dietary mineral was used as a criterion to evaluate mineral bioavailability. RESULTS: The mean concentrations of phytate, calcium and iron were significantly higher in the vegetarian meal (p=0.0002; p=0.0015 e p=0.0227, respectively), while zinc concentration was higher in the omnivorous meal (p=0.0205). Both meals presented molar ratios of phytate to calcium and phytate to iron below the critical values (1.56 and 14, respectively) suggesting that phytate in these meals should not impair calcium and iron bioavailability. The molar ratio of phytic acid to zinc in the vegetarian meal was 9.4, while in the omnivorous meal it was 4.3, characterizing them as medium and high bioavailability meals for zinc, respectively. Beans and soy were the highest sources of phytate in both meals. CONCLUSION: Due to the calcium and iron contents in both meals served in the university restaurant of the Universidade de Brasília, phytate content should not induce calcium and iron deficiency in individuals that consume these meals daily. However, given the low zinc content in the meals, phytate content may represent a risk for the development of zinc deficiency, especially in vegetarian men.

Beta-carotene from cassava (Manihot esculenta Crantz) leaves improves vitamin A status in rats.

The bioavailability of beta-carotene from cassava (Manihot esculenta Crantz) leaves was assayed in vitamin A deficient Wistar rats (Rattus norvegicus). Rats were separated into three groups and fed with a modified AIN-93G--vitamin A deficient--diet. Deficient rat received this diet without any additional vitamin A source. Controls received the diet with 7200 microg of synthetic beta-carotene (control), while experimentals (test) received 19.5 g of cassava leaves powder per kg of diet. The cassava leaves with beta-carotene promotes similar growth and tissue weight in rats to the synthetic beta-carotene. The relative bioavailability, estimated as the Retinol Accumulation Factor (RAF), was 16.5 and 27.5 for control and test groups, respectively, indicating that control and test rats should have an intake of 16.5 microg or 27.5 microg of beta-carotene from synthetic form or cassava leaves powder for each 1 microg of hepatic retinol stored, respectively. The cassava leaves beta-carotene bioavailability was lower than the synthetic beta-carotene probably because the beta-carotene from the leaf matrix may be bounded to protein complex or inside organelles, which impair carotenoid absorption. Our findings showed that beside the hepatic retinol recovery, cassava leaf beta-carotene could maintain rat growth and avoid vitamin A deficient symptoms.

Prevalência de anemia em escolares de uma comunidade rural do Distrito Federal / Anemia prevalence among schoolchildren from a rural community of Distrito Federal

Objetivo: avaliar a prevalência de anemia e a deficiência de ferro entre crianças e adolescentes de uma escola rural localizada em Planaltina, Distrito Federal. Métodos: o estudo envolveu 155 escolares de uma escola pública de área rural. Foram avaliados 83 crianças (5-9 anos) e 72 adolescentes (10-14 anos), de ambos os sexos. A dosagem de hemoglobina foi analisada em contador automático de células (Coulter T 890), e a ferritina sérica, por método quimoluminescente. O diagnóstico de anemia considerou a concentração de hemoglobina <11,5 g/dl e <12,0 g/dl para a faixa entre 5-11 e 12 -14 anos, respectivamente, enquanto o valor de ferritina <15 μg/l definiu a presença de deficiência em ferro nos escolares. Resultados: a anemia foi diagnosticada em 7,7 por cento dos escolares e a deficiência de ferro em 7,2 por cento. Entre as crianças, o diagnóstico de anemia e de deficiência de ferro alcançou 10,8 por cento e 6,4 por cento, respectivamente, enquanto entre os adolescentes, essas prevalências foram de 4,2 por cento e 8,5 por cento, respectivamente. A comparação desses resultados não mostrou diferença significativa entre as duas faixas etárias ou entre os gêneros. Conclusão: a presença de anemia nos estudantes sob estudo, embora inferior ao encontrado em outros levantamentos realizados no País, sugere ser esta doença um problema de saúde pública na comunidade que merece atenção e medidas de prevenção e tratamento, para a melhoria da qualidade de vida da população. Palavras-chave: anemia, deficiência de ferro, saúde escolar, população rural.

Papel adverso do ferro no organismo / The adverse role of iron in the organism

Introdução: devido a seu potencial redox, o ferro tornou-se o metal mais comumente utilizado na maioria dos sistemas biológicos. Nos seres vivos, exerce função essencial como cofator nas reações de transferência e conservação de energia, além de participar de vários outros processos como o transporte de oxigênio e síntese de biomoléculas. Entretanto, devido a essa versatilidade química, o ferro pode transferir elétrons para o oxigênio molecular, capazes de promover a oxidação de diversas moléculas e danos oxidativos celulares. Assim, tanto a deficiência quanto o excesso de ferro no organismo são responsáveis por um amplo espectro de doenças, variando desde a anemia até a sobrecarga. Esta revisão focaliza os recentes progressos no estudo do metabolismo e da homeostase do ferro, bem como as causas e conseqüências da deficiência e sobrecarga de ferro. Método: foram utilizadas as bases de dados Medline, Scielo e LilaCS, além de documentos governamentais e não-governamentais e sites na Internet. Considerações finais: indubitavelmente, a anemia continua sendo um dos principais problemas atuais de saúde pública, atingindo principalmente crianças menores de 24 meses e gestantes, devendo ser severamente combatida. Entretanto, o acentuado aumento da expectativa de vida ocorrido neste último meio século, que vem modificando as pirâmides demográficas de idade na direção da senilidade, tem contribuído para o aumento na prevalência de doenças crônicas não transmissíveis devido ao processo de envelhecimento. Assim, políticas de saúde pública que visam combater deficiências nutricionais devem considerar os fatores de risco para a população idosa que começa a representar uma fração significativa das populações em todos os países. Palavras-chave: ferro, anemia, estresse oxidativo, homeostase do ferro, doenças degenerativas, envelhecimento precoce.