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1.
Nutrients ; 16(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38474753

RESUMO

This study explores age- and time-dependent variations in postprandial micronutrient absorption after a micronutrient-rich intervention meal within the Biomiel (bioavailability of micronutrients in elderly) study. Comprising 43 healthy participants, the study compares young (n = 21; mean age 26.90 years) and old (n = 22; mean age 66.77 years) men and women, analyzing baseline concentrations and six-hour postprandial dynamics of iron (Fe), copper (Cu), zinc (Zn), selenium (Se), iodine (I), free zinc (fZn), vitamin C, retinol, lycopene, ß-carotene, α-tocopherol, and γ-tocopherol, along with 25(OH) vitamin D (quantified only at baseline). Methodologically, quantifications in serum or plasma were performed at baseline and also at 90, 180, 270, and 360 min postprandially. Results reveal higher baseline serum Zn and plasma lycopene concentrations in the young group, whereas Cu, Se, Cu/Zn ratio, 25(OH) vitamin D, α-tocopherol, and γ-tocopherol were higher in old participants. Postprandial variability of Zn, vitamin C, and lycopene showed a strong time-dependency. Age-related differences in postprandial metabolism were observed for Se, Cu, and I. Nevertheless, most of the variance was explained by individuality. Despite some limitations, this study provides insights into postprandial micronutrient metabolism (in serum/plasma), emphasizing the need for further research for a comprehensive understanding of this complex field. Our discoveries offer valuable insights for designing targeted interventions to address and mitigate micronutrient deficiencies in older adults, fostering optimal health and well-being across the lifespan.


Assuntos
Selênio , Oligoelementos , Masculino , Humanos , Feminino , Idoso , Adulto , Micronutrientes , Licopeno , alfa-Tocoferol , Carotenoides , gama-Tocoferol , Vitaminas , Vitamina A , Zinco , Ácido Ascórbico , Vitamina D
2.
Redox Biol ; 64: 102803, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37392516

RESUMO

Inflammatory bowel disease (IBD) is an immune-mediated gut dysfunction, which might also be associated with an inflammatory phenotype in the liver. It is known that the nutritional intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) is inversely correlated to the severity and occurrence of IBD. In order to investigate whether n-3 PUFA can also reduce liver inflammation and oxidative liver damage due to colon inflammation, we explored the dextran sulfate sodium (DSS)-induced colitis model in wild-type and fat-1 mice with endogenously increased n-3 PUFA tissue content. Besides confirming previous data of alleviated DSS-induced colitis in the fat-1 mouse model, the increase of n-3 PUFA also resulted in a significant reduction of liver inflammation and oxidative damage in colitis-affected fat-1 mice as compared to wild-type littermates. This was accompanied by a remarkable increase of established inflammation-dampening n-3 PUFA oxylipins, namely docosahexaenoic acid-derived 19,20-epoxydocosapentaenoic acid and eicosapentaenoic acid-derived 15-hydroxyeicosapentaenoic acid and 17,18-epoxyeicosatetraenoic acid. Taken together, these observations demonstrate a strong inverse correlation between the anti-inflammatory lipidome derived from n-3 PUFA and the colitis-triggered inflammatory changes in the liver by reducing oxidative liver stress.


Assuntos
Colite , Ácidos Graxos Ômega-3 , Doenças Inflamatórias Intestinais , Camundongos , Animais , Camundongos Transgênicos , Ácidos Graxos Ômega-3/efeitos adversos , Colite/induzido quimicamente , Colite/genética , Inflamação/genética , Fígado , Estresse Oxidativo
3.
Nutrients ; 15(9)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37432362

RESUMO

An inadequate selenium (Se) status can accelerate the aging process, increasing the vulnerability to age-related diseases. The study aimed to investigate plasma Se and Se species in a large population, including 2200 older adults from the general population (RASIG), 514 nonagenarian offspring (GO), and 293 GO Spouses (SGO). Plasma Se levels in women exhibit an inverted U-shaped pattern, increasing with age until the post-menopausal period and then declining. Conversely, men exhibit a linear decline in plasma Se levels with age. Subjects from Finland had the highest plasma Se values, while those from Poland had the lowest ones. Plasma Se was influenced by fish and vitamin consumption, but there were no significant differences between RASIG, GO, and SGO. Plasma Se was positively associated with albumin, HDL, total cholesterol, fibrinogen, and triglycerides and negatively associated with homocysteine. Fractionation analysis showed that Se distribution among plasma selenoproteins is affected by age, glucometabolic and inflammatory factors, and being GO or SGO. These findings show that sex-specific, nutritional, and inflammatory factors play a crucial role in the regulation of Se plasma levels throughout the aging process and that the shared environment of GO and SGO plays a role in their distinctive Se fractionation.


Assuntos
Selênio , Feminino , Humanos , Animais , Masculino , Nonagenários , Vitaminas , Comportamento Alimentar
4.
Nat Commun ; 14(1): 3479, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37311819

RESUMO

Selenium homeostasis depends on hepatic biosynthesis of selenoprotein P (SELENOP) and SELENOP-mediated transport from the liver to e.g. the brain. In addition, the liver maintains copper homeostasis. Selenium and copper metabolism are inversely regulated, as increasing copper and decreasing selenium levels are observed in blood during aging and inflammation. Here we show that copper treatment increased intracellular selenium and SELENOP in hepatocytes and decreased extracellular SELENOP levels. Hepatic accumulation of copper is a characteristic of Wilson's disease. Accordingly, SELENOP levels were low in serum of Wilson's disease patients and Wilson's rats. Mechanistically, drugs targeting protein transport in the Golgi complex mimicked some of the effects observed, indicating a disrupting effect of excessive copper on intracellular SELENOP transport resulting in its accumulation in the late Golgi. Our data suggest that hepatic copper levels determine SELENOP release from the liver and may affect selenium transport to peripheral organs such as the brain.


Assuntos
Degeneração Hepatolenticular , Selênio , Animais , Ratos , Selenoproteína P , Cobre
5.
Redox Biol ; 64: 102762, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37302344

RESUMO

Maintenance peritoneal dialysis (PD) is commonly associated with cardiovascular diseases (CVDs), whose risk is assessed via LDL-C. Nonetheless, oxidized LDL (oxLDL), as being a key component of atherosclerotic lesions, could be also associated with atherosclerosis and related CVDs. However, its predictive value for CVDs risk assessment is subject of research studies due to the lack of specific methods to measure oxLDL status from its individual lipid/protein components. In the present study, six novel oxLDL markers, representative of certain oxidative modifications on the LDL protein and lipid components, are measured in atherosclerosis-prone PD patients (39) versus those in chronic kidney disease patients (61) under hemodialysis (HD) and healthy controls (40). LDL from serum of PD, HD and control subjects were isolated and fractionated into cholesteryl esters, triglycerides, free cholesterol, phospholipids and apolipoprotein B100 (apoB100). Subsequently the oxLDL markers cholesteryl ester hydroperoxides (-OOH), triglyceride-OOH, free cholesterol-OOH, phospholipid-OOH, apoB100 malondialdehyde and apoB100 dityrosines were measured. LDL carotenoid levels and LDL particle serum concentration were also measured. The levels of all oxLDL lipid-OOH markers were significantly elevated in PD patients versus control, while the levels of cholesteryl ester-/triglyceride-/free cholesterol-OOH were significantly elevated in PD versus HD patients, regardless of patients' underlying medical conditions, sex, age, PD type, clinical biochemical markers and medication. It should be noted that all fractionated lipid-OOH levels were inversely correlated with LDL-P concentration, while LDL-P concentration was not correlated with LDL-C in PD patients. Moreover, LDL carotenoids were significantly lower in PD patients versus control. The increased levels of oxLDL status specific markers in both PD and HD patients (compared to control), support a potential prognostic value of oxLDL regarding CVD risk assessment in both patient groups. Lastly, the study introduces the oxLDL peroxidation markers free cholesterol-OOH and cholesteryl ester-OOH as complementary to LDL-P number, and as possible alternatives to LDL-C.


Assuntos
Aterosclerose , Diálise Peritoneal , Humanos , Ésteres do Colesterol , LDL-Colesterol , Lipoproteínas LDL/metabolismo , Diálise Peritoneal/efeitos adversos , Biomarcadores , Colesterol , Aterosclerose/etiologia , Medição de Risco , Fosfolipídeos , Triglicerídeos
6.
Redox Biol ; 57: 102490, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36182809

RESUMO

Mice with constitutive disruption of the Selenop gene have been key to delineate the importance of selenoproteins in neurobiology. However, the phenotype of this mouse model is exquisitely dependent on selenium supply and timing of selenium supplementation. Combining biochemical, histological, and behavioral methods, we tested the hypothesis that parvalbumin-expressing interneurons in the primary somatosensory cortex and hippocampus depend on dietary selenium availability in Selenop-/- mice. Selenop-deficient mice kept on adequate selenium diet (0.15 mg/kg, i.e. the recommended dietary allowance, RDA) developed ataxia, tremor, and hyperexcitability between the age of 4-5 weeks. Video-electroencephalography demonstrated epileptic seizures in Selenop-/- mice fed the RDA diet, while Selenop± heterozygous mice behaved normally. Both neurological phenotypes, hyperexcitability/seizures and ataxia/dystonia were successfully prevented by selenium supplementation from birth or transgenic expression of human SELENOP under a hepatocyte-specific promoter. Selenium supplementation with 10 µM selenite in the drinking water on top of the RDA diet increased the activity of glutathione peroxidase in the brains of Selenop-/- mice to control levels. The effects of selenium supplementation on the neurological phenotypes were dose- and time-dependent. Selenium supplementation after weaning was apparently too late to prevent ataxia/dystonia, while selenium withdrawal from rescued Selenop-/- mice eventually resulted in ataxia. We conclude that SELENOP expression is essential for preserving interneuron survival under limiting Se supply, while SELENOP appears dispensable under sufficiently high Se status.

7.
Nutr Diabetes ; 12(1): 20, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35418570

RESUMO

OBJECTIVE: Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake. METHODS: To address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes). RESULTS: Here, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure-likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3-HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling. CONCLUSION: These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance.


Assuntos
Aminoácidos de Cadeia Ramificada , Resistência à Insulina , Animais , Glucose/metabolismo , Resistência à Insulina/fisiologia , Leucina/metabolismo , Leucina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Valina/metabolismo , Valina/farmacologia
8.
Nutrients ; 11(3)2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30866427

RESUMO

For centuries, Amaranthus sp. were used as food, ornamentals, and medication. Molecular mechanisms, explaining the health beneficial properties of amaranth, are not yet understood, but have been attributed to secondary metabolites, such as phenolic compounds. One of the most abundant phenolic compounds in amaranth leaves is 2-caffeoylisocitric acid (C-IA) and regarding food occurrence, C-IA is exclusively found in various amaranth species. In the present study, the anti-inflammatory activity of C-IA, chlorogenic acid, and caffeic acid in LPS-challenged macrophages (RAW 264.7) has been investigated and cellular contents of the caffeic acid derivatives (CADs) were quantified in the cells and media. The CADs were quantified in the cell lysates in nanomolar concentrations, indicating a cellular uptake. Treatment of LPS-challenged RAW 264.7 cells with 10 µM of CADs counteracted the LPS effects and led to significantly lower mRNA and protein levels of inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin 6, by directly decreasing the translocation of the nuclear factor κB/Rel-like containing protein 65 into the nucleus. This work provides new insights into the molecular mechanisms that attribute to amaranth's anti-inflammatory properties and highlights C-IA's potential as a health-beneficial compound for future research.


Assuntos
Amaranthus/química , Anti-Inflamatórios/farmacologia , Ácidos Cafeicos/farmacologia , Isocitratos/farmacologia , NF-kappa B/metabolismo , Animais , Ácidos Cafeicos/química , Citocinas/metabolismo , Isocitratos/química , Lipopolissacarídeos/efeitos adversos , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
9.
Redox Biol ; 14: 47-58, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28866248

RESUMO

Association of oxidative stress with carcinogenesis is well known, but not understood well, as is pathophysiology of oxidative stress generated during different types of anti-cancer treatments. Moreover, recent findings indicate that cancer associated lipid peroxidation might eventually help defending adjacent nonmalignant cells from cancer invasion. Therefore, untargeted metabolomics studies designed for advanced translational and clinical studies are needed to understand the existing paradoxes in oncology, including those related to controversial usage of antioxidants aiming to prevent or treat cancer. In this short review we have tried to put emphasis on the importance of pathophysiology of oxidative stress and lipid peroxidation in cancer development in relation to metabolic adaptation of particular types of cancer allowing us to conclude that adaptation to oxidative stress is one of the main driving forces of cancer pathophysiology. With the help of metabolomics many novel findings are being achieved thus encouraging further scientific breakthroughs. Combined with targeted qualitative and quantitative methods, especially immunochemistry, further research might reveal bio-signatures of individual patients and respective malignant diseases, leading to individualized treatment approach, according to the concepts of modern integrative medicine.


Assuntos
Metabolômica , Neoplasias/fisiopatologia , Estresse Oxidativo , Biomarcadores Tumorais/metabolismo , Glutationa/química , Glutationa/metabolismo , Humanos , Redes e Vias Metabólicas , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
10.
J Nutr Biochem ; 48: 112-119, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28810182

RESUMO

The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism. Accordingly, the impact of Se on global DNA methylation, methylation capacity, and gene expression was assessed. We observed higher global DNA methylation indicated by LINE1 methylation, and an increase of the methylation potential as indicated by higher S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio and by elevated mRNA expression of serine hydroxymethyltransferase in both or either of the Se groups. Furthermore, increasing the Se supply resulted in higher plasma concentrations of triglycerides. Hepatic expression of glycolytic and lipogenic genes revealed consistent Se-dependent up-regulation of glucokinase. The sterol regulatory element-binding transcription factor 1 (Srebf1) was also up-regulated by Se. Both effects were confirmed in primary hepatocytes. In contrast to the overall Se-dependent increase of methylation capacity, the up-regulation of Srebf1 expression was paralleled by reduced local methylation of a specific CpG site within the Srebf1 gene. Thus, we provided evidence that Se-dependent effects on lipogenesis involve epigenetic mechanisms.


Assuntos
Carbono/metabolismo , Metilação de DNA/efeitos dos fármacos , Fígado/efeitos dos fármacos , Selênio/farmacologia , Animais , Glicina Hidroximetiltransferase/genética , Glicólise/efeitos dos fármacos , Glicólise/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Camundongos Endogâmicos C57BL , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Triglicerídeos/sangue , Regulação para Cima/efeitos dos fármacos
11.
Curr Opin Clin Nutr Metab Care ; 20(5): 349-359, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28562491

RESUMO

PURPOSE OF REVIEW: The aim of this article is to present a brief overview of recently published articles assessing oxidative stress markers in nutritional studies. RECENT FINDINGS: Intervention and observational studies were carried out in both, healthy subjects and patients and describe the association of foodstuffs as well as isolated nutrients with biomarkers of oxidative stress. The results from human intervention studies on healthy participants and patients are controversial. Long-term interventions (>8 weeks) seem to be more effective than short-term or single-dose interventions. Results are difficult to compare because not only the methods used, also the assessed biomarkers and outcomes were very diverse. In addition, studies vary in the compounds and doses used, duration, participants and so on. Different biomarkers (damaged molecules together with antioxidants from different compartments) should be assessed to evaluate the true 'redox-status' of an individual and the impact of a nutritional intervention. SUMMARY: Both observational and interventional studies performed in healthy participants and patients show possible beneficial effects of nutrients and foodstuffs by improving oxidative stress markers and antioxidant enzyme activities. Biomarkers should be standardized to allow better comparison of results of antioxidant intervention studies.


Assuntos
Antioxidantes/uso terapêutico , Doença Crônica/prevenção & controle , Dieta Saudável , Envelhecimento Saudável , Estresse Oxidativo , Cooperação do Paciente , Animais , Antioxidantes/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Suplementos Nutricionais , Alimento Funcional , Humanos , Reprodutibilidade dos Testes
12.
Nutrients ; 8(10)2016 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-27706032

RESUMO

Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/ß-carotene and higher ß-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene (r = -0.248), α-tocopherol (r = 0.208), α-carotene (r = -0.112), and ß-cryptoxanthin (r = 0.125; all p < 0.001). Age was inversely associated with lycopene (-6.5% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m²)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7% vs. 2.4% per five-year age increase). The association of higher ß-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (-4.8% vs. -3.8% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene.


Assuntos
Carotenoides/sangue , Tocoferóis/sangue , Vitamina A/sangue , Adulto , Fatores Etários , Idoso , beta-Criptoxantina/sangue , Estudos Transversais , Dieta , Europa (Continente) , Feminino , Frutas , Humanos , Luteína/sangue , Licopeno , Masculino , Pessoa de Meia-Idade , Zeaxantinas/sangue , alfa-Tocoferol/sangue , beta Caroteno/sangue , gama-Tocoferol/sangue
13.
Ann Med ; 48(8): 614-624, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27320287

RESUMO

Insulin-degrading enzyme (IDE) is a major enzyme responsible for insulin degradation. In addition to insulin, IDE degrades many targets including glucagon, atrial natriuretic peptide, and beta-amyloid peptide, regulates proteasomal degradation and other cell functions. IDE represents a pathophysiological link between type 2 diabetes (T2DM) and late onset Alzheimer's disease (AD). Potent and selective modulators of IDE activity are potential drugs for therapies of both diseases. Acute treatment with a novel IDE inhibitor was recently tested in a mouse study as a therapeutic approach for the treatment of T2DM. In contrast, effective IDE activators can be used for the AD treatment. However, because of the pleiotropic IDE action, the sustained treatment with systemic IDE modulators should be carefully tested in animal studies. Development of substrate-selective IDE modulators could overcome possible adverse effects of IDE modulators associated with multiplicity of IDE targets. KEY MESSAGES Insulin-degrading enzyme (IDE) represents a pathophysiological link between type 2 diabetes (T2DM) and Alzheimer's disease (AD). Selective modulators of IDE activity are potential drugs for both T2DM and AD treatment. Development of substrate-selective IDE modulators could overcome possible adverse effects of IDE modulators associated with multiplicity of IDE targets.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Insulisina/antagonistas & inibidores , Doença de Alzheimer/enzimologia , Doença de Alzheimer/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/farmacologia , Humanos , Camundongos , Terapia de Alvo Molecular
14.
Biofactors ; 42(3): 307-15, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27095633

RESUMO

Considering the biological function of α-tocopherol (α-Toc) as a potent protective factor against oxidative stress, this antioxidant is in the focus of aging research. To understand the role of α-Toc during aging we investigated α-Toc concentrations in young and aged primary human fibroblasts after supplementation with RRR-α-Toc. Additionally, α-Toc contents were determined in brain, kidney, and liver tissue of 10 week-, 18 month-, and 24 month-old mice, which were fed a standard diet containing 100 mg/kg dl-α-tocopheryl acetate. α-Toc concentrations in isolated lysosomes and the expression of the α-Toc transport proteins Niemann Pick C1 (NPC1), Niemann Pick C2 (NPC2), and lipoprotein lipase were also analyzed. Obtained data show a significant age-related increase of α-Toc in murine liver, kidney, and brain tissue as well as in human dermal fibroblasts. Also liver and kidney lysosomes are marked by elevated α-Toc contents with aging. NPC1 and NPC2 protein amounts are significantly decreased in adult and aged murine kidney tissue. Also aged human dermal fibroblasts show decreased NPC1 amounts. Supplementation of young and aged fibroblasts led also to decreased NPC1 amounts, suggesting a direct role of this protein in α-Toc distribution. Our results indicate an age-dependent increase of α-Toc in different murine tissues as well as in human fibroblasts. Furthermore saturation and intracellular distribution of α-Toc seem to be strongly dependent on the availability of this vitamin as well as on the presence of the lysosomal protein NPC1. © 2016 BioFactors, 42(3):307-315, 2016.


Assuntos
Envelhecimento/metabolismo , Proteínas de Transporte/biossíntese , Fibroblastos/metabolismo , Lisossomos/metabolismo , Glicoproteínas de Membrana/biossíntese , alfa-Tocoferol/metabolismo , Adulto , Envelhecimento/genética , Envelhecimento/patologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas de Transporte/genética , Fibroblastos/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas/biossíntese , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Rim/metabolismo , Rim/patologia , Lipase Lipoproteica/biossíntese , Fígado/metabolismo , Fígado/patologia , Lisossomos/patologia , Masculino , Glicoproteínas de Membrana/genética , Camundongos , Proteína C1 de Niemann-Pick , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Transporte Vesicular , alfa-Tocoferol/administração & dosagem
15.
Nutrients ; 8(2): 66, 2016 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26821044

RESUMO

Micronutrient fortified flour (MFF), supplementary food rations and micronutrient (MN) supplements may prevent deficiencies among pregnant women. Objectives of cross-sectional surveys in 2004 (n = 533) and 2006 (n = 515) were to assess the impact of new food rations (flour, oil) and supplements on MN status by trimester of pregnancy in the Maela refugee camp. Hemoglobin, iron status, zinc, retinol, ß-carotene and tryptophan decreased, while α-/γ-tocopherol and 5-methyltetrahydrofolate (5-MTHF) increased from first to third trimester. In 2006, mean zinc and α-tocopherol for each trimester was significantly higher than in 2004. The weeks of supplemented thiamine and folic acid were positively correlated with thiamine diphosphate (TDP) and 5-MTHF, but not for ferrous sulfate as iron deficiency was observed in 38.5% of third-trimester women. Frequent consumption of fish paste and owning a garden or animal were associated with significantly higher iron status, retinol, ß-carotene, and 5-MTHF. In conclusion, MFF and supplementary oil were most likely to explain improved zinc and α-tocopherol status, while thiamine and folate supplements ensured high TDP and 5-MTHF in late pregnancy. MN supplements, MN-rich staple food, small gardens, and programs to improve iron compliance are promising strategies to prevent MN deficiencies during pregnancy in vulnerable populations.


Assuntos
Deficiências Nutricionais/prevenção & controle , Dieta , Suplementos Nutricionais , Assistência Alimentar , Micronutrientes/uso terapêutico , Trimestres da Gravidez , Refugiados , Adulto , Comportamento Alimentar , Feminino , Alimentos , Jardinagem , Humanos , Micronutrientes/sangue , Micronutrientes/deficiência , Estado Nutricional , Gravidez , Tailândia , Populações Vulneráveis , Adulto Jovem
16.
Epigenetics ; 10(3): 179-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25647085

RESUMO

Alterations of epigenetic marks are linked to normal development and cellular differentiation as well as to the progression of common chronic diseases. The plasticity of these marks provides potential for disease therapies and prevention strategies. Macro- and micro-nutrients have been shown to modulate disease risk in part via effects on the epigenome. The essential micronutrient selenium affects human health outcomes, e.g., cancers, cardiovascular and autoimmune diseases, via selenoproteins and through a range of biologically active dietary selenocompounds and metabolism products thereof. This review provides an assessment of the current literature regarding epigenetic effects of dietary and synthetic selenocompounds, which include the modulation of marks and editors of epigenetic information and interference with one-carbon metabolism, which provides the methyl donor for DNA methylation. The relevance of a selenium-epigenome interaction for human health is discussed, and we also indicate where future studies will be helpful to gain a deeper understanding of epigenetic effects elicited by selenium.


Assuntos
Epigênese Genética , Selênio/metabolismo , Animais , Carbono/metabolismo , DNA/metabolismo , Metilação de DNA , Histonas/metabolismo , Humanos , Selênio/química
17.
Nutrients ; 6(9): 3624-40, 2014 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-25221976

RESUMO

Polyunsaturated fatty acids (PUFAs), especially the n-3 series, are known for their protective effects. Considering that cardiovascular diseases are risk factors for dementia, which is common at aging, the aim of this study was to evaluate whether fatty acid status in the elderly was associated with cognitive function and cardiovascular risk. Forty-five elderly persons (age ≥ 60 years) were included and divided into two groups based on their Mini-Mental Status Examination score adjusted for educational level: the case group (n = 12) and the control group (n = 33). Serum fatty acid composition, homocysteine (Hcy), hs-CRP, lipid profile and different cognitive domains were evaluated. The case group, characterized by reduced cognitive performance, showed higher levels of 14:0, 16:0, 16:1n-7 fatty acids and lower levels of 22:0, 24:1n-9, 22:6n-3 (DHA) and total PUFAs compared to the control group (p < 0.05). The n-6/n-3 ratio was elevated in both study groups, whereas alterations in Hcy, hs-CRP and lipid profile were observed in the case group. Cognitive function was positively associated with the 24:1n-9, DHA and total n-3 PUFAs, while 14:0, 16:0 and 16:1n-7 fatty acids, the n-6/n-3 ratio and Hcy were inversely associated. In addition, n-3 PUFAs, particularly DHA, were inversely associated with cardiovascular risk, assessed by Hcy levels in the elderly.


Assuntos
Transtornos Cognitivos/sangue , Cognição , Demência/sangue , Ácidos Graxos Insaturados/sangue , Homocisteína/sangue , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/etiologia , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Transtornos Cognitivos/etiologia , Demência/etiologia , Dieta , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Feminino , Avaliação Geriátrica , Humanos , Lipídeos/sangue , Masculino , Memória , Fatores de Risco
18.
Biofactors ; 40(3): 346-54, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24578032

RESUMO

Coenzyme Q derivatives (CoQ) are lipid soluble antioxidants that are synthesized endogenously in almost all species and function as an obligatory cofactor of the respiratory chain. There is evidence that CoQ status is altered by age in several species. Here we determined level and redox-state of CoQ in different age groups of pigs, mice and Caenorhabditis elegans. Since these species are very different with respect to lifespan, reproduction and physiology, our approach could provide some general tendencies of CoQ status in ageing organisms. We found that CoQ level decreases with age in pigs and mice, whereas CoQ content increases in older worms. As observed in all three species, ubiquinone, the oxidized form of CoQ, increases with age. Additionally, we were able to show that supplementation of ubiquinol-10, the reduced form of human CoQ10 , slightly increases lifespan of post-reproductive worms. In conclusion, the percentage of the oxidized form of CoQ increases with age indicating higher oxidative stress or rather a decreased anti-oxidative capacity of aged animals.


Assuntos
Envelhecimento/metabolismo , Estresse Oxidativo , Ubiquinona/metabolismo , Animais , Caenorhabditis elegans , Feminino , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Especificidade da Espécie , Sus scrofa
19.
Rejuvenation Res ; 15(1): 71-81, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22236145

RESUMO

A Mediterranean diet rich in olive oil has been associated with health benefits in humans. It is unclear if and to what extent olive oil phenolics may mediate these health benefits. In this study, we fed senescence-accelerated mouse-prone 8 (SAMP8, n=11 per group) semisynthetic diets with 10% olive oil containing either high (HP) or low amounts of olive oil phenolics (LP) for 4.5 months. Mice consuming the HP diet had significantly lower concentrations of the oxidative damage markers thiobarbituric acid-reactive substances and protein carbonyls in the heart, whereas proteasomal activity was similar in both groups. Nrf2-dependent gene expression may be impaired during the aging process. Therefore, we measured Nrf2 and its target genes glutathione-S-transferase (GST), γ-glutamyl cysteine synthetase (γ-GCS), nicotinamide adenine dinucleotide phosphate [NAD(P)H]:quinone oxidoreductase (NQO1), and paraoxonase-2 (PON2) in the hearts of these mice. Nrf2 as well as GST, γ-GCS, NQO1, and PON2 mRNA levels were significantly higher in heart tissue of the HP as compared to the LP group. The HP-fed mice had significantly higher PON1 activity in serum compared to those receiving the LP diet. Furthermore, HP feeding increased relative SIRT1 mRNA levels. Additional mechanistic cell culture experiments were performed, and they suggest that the olive oil phenolic hydroxytyrosol present in the HP oil may be responsible for the induction of Nrf2-dependent gene expression and the increase in PON activity. In conclusion, a diet rich in olive oil phenolics may prevent oxidative stress in the heart of SAMP8 mice by modulating Nrf2-dependent gene expression.


Assuntos
Regulação da Expressão Gênica , Miocárdio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Óleos de Plantas/metabolismo , Envelhecimento , Ração Animal , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Senescência Celular , Feminino , Ferro/química , Peroxidação de Lipídeos , Camundongos , Azeite de Oliva , Oxidantes/metabolismo , Estresse Oxidativo , Fenol/química , Espectrofotometria/métodos
20.
Biofactors ; 37(1): 17-24, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21328623

RESUMO

Photodynamic therapy (PDT) is an important clinical approach for cancer treatment. It involves the administration of a photosensitizer, followed by its activation with light and induction of cell death. The underlying mechanism is an increased production of reactive oxygen species (ROS) leading to oxidative stress, which is followed by cell death. However, effectiveness of PDT is limited due to an initiation of endogenous rescue response systems like heme oxygenase-1 (HO-1) in tumor cells. In recent years, consuming of antioxidant supplements has become widespread, but the effect of exogenously applied antioxidants on cancer therapy outcome remains unclear. Thus, this study was aimed to investigate if exogenous antioxidants might decrease ROS-induced cytotoxicity in photodynamic treatment. Lycopene, ß-carotene, vitamin C, N-acetylcysteine, trolox, and N-tert-butyl-α-phenylnitrone in different doses were administered to human melanoma cells prior exposure to photodynamic treatment. Supplementation with vitamin C resulted in a significant decrease of the cell death rate, whereas the other tested antioxidants had no effect on cell viability and oxidative stress markers. The simultaneous application of vitamin C with the HO-1 activity inhibitor zinc protoporphyrine IX (ZnPPIX) caused a considerable decrease of photodynamic treatment-induced cytotoxicity compared to ZnPPIX alone. It can be summarized that exogenously applied antioxidants do not have a leading role in the protective response against photodynamic treatment. However, further studies are necessary to investigate more antioxidants and other substances, which might affect the outcome of photodynamic treatment in cancer therapy.


Assuntos
Ácido Aminolevulínico/farmacologia , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Heme Oxigenase-1/metabolismo , Melanoma/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Heme Oxigenase-1/antagonistas & inibidores , Humanos , Melanoma/tratamento farmacológico , Estresse Oxidativo , Protoporfirinas/farmacologia , Regulação para Cima
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