RESUMO
UNLABELLED: With no approved pharmacological treatment, nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in Western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here, we show that a high-fat high-sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic nicotinamide adenine dinucleotide (NAD(+) ) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation in C57BL/6J mice. To assess the effect of NAD(+) repletion on the development of steatosis in mice, nicotinamide riboside, a precursor of NAD(+) biosynthesis, was added to the HFHS diet, either as a preventive strategy or as a therapeutic intervention. We demonstrate that NR prevents and reverts NAFLD by inducing a sirtuin (SIRT)1- and SIRT3-dependent mitochondrial unfolded protein response, triggering an adaptive mitohormetic pathway to increase hepatic ß-oxidation and mitochondrial complex content and activity. The cell-autonomous beneficial component of NR treatment was revealed in liver-specific Sirt1 knockout mice (Sirt1(hep-/-) ), whereas apolipoprotein E-deficient mice (Apoe(-/-) ) challenged with a high-fat high-cholesterol diet affirmed the use of NR in other independent models of NAFLD. CONCLUSION: Our data warrant the future evaluation of NAD(+) boosting strategies to manage the development or progression of NAFLD.
Assuntos
Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/patologia , NAD/metabolismo , Niacinamida/análogos & derivados , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Análise de Variância , Animais , Área Sob a Curva , Biópsia por Agulha , Dieta Hiperlipídica/métodos , Modelos Animais de Doenças , Fígado Gorduroso/metabolismo , Imuno-Histoquímica , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NAD/efeitos dos fármacos , Niacinamida/farmacologia , Compostos de Piridínio , Distribuição Aleatória , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a subset of non-alcoholic fatty liver disease, the most common chronic liver disease in the U.S. Fibrosis, a common feature of NASH, results from the dysregulation of fibrogenesis in hepatic stellate cells (HSCs). In this study, we investigated whether astaxanthin (ASTX), a xanthophyll carotenoid, can inhibit fibrogenic effects of transforming growth factor ß1 (TGFß1), a key fibrogenic cytokine, in HSCs. METHODS: Reactive oxygen species (ROS) accumulation was measured in LX-2, an immortalized human HSC cell line. Quantitative realtime PCR, Western blot, immunocytochemical analysis, and in-cell Western blot were performed to determine mRNA and protein of fibrogenic genes, and the activation of Smad3 in TGFß1-activated LX-2 cells and primary mouse HSCs. RESULTS: In LX-2 cells, ROS accumulation induced by tert-butyl hydrogen peroxide and TGFß1 was abolished by ASTX. ASTX significantly decreased TGFß1-induced α-smooth muscle actin (α-SMA) and procollagen type 1, alpha 1 (Col1A1) mRNA as well as α-SMA protein levels. Knockdown of Smad3 showed the significant role of Smad3 in the expression of α-SMA and Col1A1, but not TGFß1, in LX-2 cells. ASTX attenuated TGFß1-induced Smad3 phosphorylation and nuclear translocation with a concomitant inhibition of Smad3, Smad7, TGFß receptor I (TßRI), and TßRII expression. The inhibitory effect of ASTX on HSC activation was confirmed in primary mouse HSCs as evidenced by decreased mRNA and protein levels of α-SMA during activation. CONCLUSION: Taken together, ASTX exerted anti-fibrogenic effects by blocking TGFß1-signaling, consequently inhibiting the activation of Smad3 pathway in HSCs. GENERAL SIGNIFICANCE: This study suggests that ASTX may be used as a preventive/therapeutic agent to prevent hepatic fibrosis.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Actinas/genética , Actinas/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Western Blotting , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Relação Dose-Resposta a Droga , Fibrinolíticos/farmacologia , Fibrose/genética , Células Estreladas do Fígado/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Músculo Liso/química , Fosforilação/efeitos dos fármacos , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Smad3/genética , Xantofilas/farmacologiaRESUMO
Prostate cancer is the most common non-cutaneous cancer and the second leading cause of cancer-related mortality among men in the USA. Growing evidence suggests that oxidative stress is involved in the development and progression of prostate cancer. In this study, the association between antioxidants from diet and supplements and biomarkers of oxidative stress in blood (n 278), urine (n 298) and prostate tissue (n 55) were determined among men from the North Carolina-Louisiana Prostate Cancer Project. The association between antioxidant intake and oxidative stress biomarkers in blood and urine was determined using linear regression, adjusting for age, race, prostate cancer aggressiveness and smoking status. Greater antioxidant intake was found to be associated with lower urinary 8-isoprostane concentrations, with a 10% increase in antioxidant intake corresponding to an unadjusted 1·1% decrease in urinary 8-isoprostane levels (95% CI -1·7, -0·3%; P value<0·01) and an adjusted 0·6% decrease (95% CI -1·4, 0·2%; P value=0·16). In benign prostate tissue, thioredoxin 1 was inversely associated with antioxidant intake (P=0·02). No significant associations were found for other blood or urinary biomarkers or for malignant prostate tissue. These results indicate that antioxidant intake may be associated with less oxidative stress among men diagnosed with prostate cancer.
Assuntos
Antioxidantes/farmacologia , Dieta , Suplementos Nutricionais , Dinoprosta/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Tiorredoxinas/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Dinoprosta/urina , Comportamento Alimentar , Humanos , Louisiana , Masculino , Pessoa de Meia-Idade , North Carolina , Próstata/metabolismo , Próstata/patologiaRESUMO
To estimate daily intake of total phenolics and flavonoids from green tea and the contribution of green tea to the antioxidant intake from the Korean diet, 24 commercial brands of green tea were selected and analyzed. Data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 and 2011 indicate that the green tea consumption in these 2 years was 2.8 g/tea drinker/day and 2.9 g/tea drinker/day, respectively. Based on data derived from direct measurements of green tea phenolics and the dataset of the 2008 KNHANES, we estimated the daily per tea drinker phenolics intake to be 172 mg gallic acid equivalents (GAE), the total flavonoids to be 43 mg catechin equivalents (CE) and the total antioxidants to be 267 mg vitamin C equivalents (VCE; 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay) and 401 mg VCE (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assay). In 2011, we estimated the daily per tea drinker total phenolics intake to be 246 mg GAE, the total flavonoids to be 60 mg CE and the antioxidants to be 448 mg VCE (DPPH assay) and 630 mg VCE (ABTS assay). The daily intake of total phenolics, total flavonoids and antioxidants from green tea consumption increased from 2008 to 2011.
Assuntos
Antioxidantes/administração & dosagem , Fenóis/administração & dosagem , Chá/química , Antioxidantes/química , Benzotiazóis , Compostos de Bifenilo , Dieta , Comportamento Alimentar , Flavonoides/administração & dosagem , Flavonoides/química , Humanos , Inquéritos Nutricionais , Fenóis/química , Picratos , República da Coreia , Ácidos SulfônicosRESUMO
The present study aimed to evaluate the contribution of anthocyanin composition to the total antioxidant capacity (TAC) of berries having different anthocyanin composition; blackberry, black currant, and blueberry. Blackberry demonstrated the highest TAC, while it had the lowest total anthocyanin content among the three berries in both of the phenolic extract and anthocyanin fractions. On the other hand, black currant had the highest total anthocyanin content, but the lowest TAC. Cyanidin-3-O-glucoside (cya-3-glc) accounted for 94% of blackberry anthocyanins, and as one of the strongest antioxidants present in these three berries, it substantially contributed to the TAC of blackberry anthocyanin fraction (96.0%). Delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside in black currant had lower antioxidant capacities compared with delphinin-3-O-glucoside and cya-3-glc, resulting in its lowest TAC among berry anthocyanin fractions examined. Malvidin derivatives, major anthocyanins of blueberry, had considerably lower antioxidant capacity than other anthocyanidin derivatives, such as cyanidin or delphinidin, resulting in lower TAC of blueberry compared with blackberry. Our findings indicate that anthocyanin composition as well as the antioxidant capacity of individual anthocyanins contributes to the TAC of berries rich in distinct anthocyanins.
Assuntos
Antocianinas/análise , Antioxidantes/análise , Frutas/química , Mirtilos Azuis (Planta)/química , Ribes/química , Rubus/químicaRESUMO
Hyperlipidemia and elevated circulating C-reactive protein (CRP) and total homocysteine (tHcy) concentrations are cardiovascular disease (CVD) risk factors. Previous studies indicated that higher serum carotenoid concentrations were inversely associated with some of these biomarkers. However, whether dietary carotenoid intake is inversely associated with these CVD risk biomarkers is not well known. We assessed the associations between individual dietary carotenoid intake and CVD risk biomarkers and tested whether the serum carotenoid concentrations explain (mediate) or influence the strength of (moderate) the associations, if any association exists. Dietary data collected from 2 24-h dietary recalls and serum measurements in adult men (n = 1312) and women (n = 1544) from the NHANES 2003-2006 were used. Regression models designed for survey analysis were used to examine the associations between individual dietary carotenoids and log-transformed blood cholesterol, CRP, and tHcy. The corresponding individual serum carotenoid concentration was considered as mediator (and moderator if applicable). After adjustment for covariates, significant inverse associations with LDL cholesterol were observed for dietary ß-carotene (P < 0.05) and lutein + zeaxanthin (P < 0.001), and with tHcy for dietary ß-carotene (P < 0.05), lycopene (P < 0.05), and total carotenoids (P < 0.05). Dietary lutein + zeaxanthin intake was also positively associated with HDL cholesterol concentrations (P < 0.01). Most of these associations were null after additional adjustment for corresponding serum carotenoid concentrations, indicating the complete mediation effects of serum carotenoids. Serum ß-carotene significantly moderated the associations between dietary ß-carotene and CRP (P-interaction < 0.05), and quartile 4 of dietary ß-carotene was associated with lower CRP concentrations only among participants with serum ß-carotene > 0.43 µmol/L. In this population-based cross-sectional study, serum carotenoids were mediators of dietary carotenoids and CVD risk biomarker associations. Serum ß-carotene was also a moderator of the dietary ß-carotene and CRP association. These findings may help in the design of future intervention studies on dietary carotenoids in the prevention of CVD.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Carotenoides/uso terapêutico , Dieta , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Carotenoides/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Dieta/efeitos adversos , Feminino , Homocisteína/sangue , Humanos , Hipercolesterolemia/fisiopatologia , Hiper-Homocisteinemia/fisiopatologia , Luteína/sangue , Luteína/uso terapêutico , Licopeno , Masculino , Inquéritos Nutricionais , Fatores de Risco , Estados Unidos/epidemiologia , Xantofilas/sangue , Xantofilas/uso terapêutico , Zeaxantinas , beta Caroteno/sangue , beta Caroteno/uso terapêuticoRESUMO
BACKGROUND: Previous studies have shown that total antioxidant capacity (TAC) of typical diets is associated with higher plasma TAC and antioxidant enzyme activities. At present, however, little is known for the association between dietary TAC and inflammatory biomarkers. AIM: The present study was designed to examine the association between dietary TAC and inflammatory biomarkers in a group of overweight/obese postmenopausal women, a population with high cardiovascular disease (CVD) risk, during a 9-month period. METHODS: Thirty-five postmenopausal, overweight or obese, but apparently healthy women aged 40-70 years were recruited for a 9-month observational study. Seven-day food records and 12-h fasting blood samples were collected at baseline and at the end of the study for dietary and plasma biomarker assessments. Dietary TAC was calculated theoretically for taking account of both diet and dietary supplements, and energy-adjusted values were obtained using residual method. RESULTS: At baseline, subjects consuming diets with high dietary TAC had lower levels of plasma C-reactive protein (CRP) and monocyte chemoattractant protein-1 (p < 0.05) compared with those with low dietary TAC. Over the 9-month period, change in dietary TAC had a negative partial correlation with plasma CRP levels (p < 0.01) when age, ethnicity, and changes in BMI, blood total cholesterol and triglyceride were adjusted. CONCLUSIONS: Findings suggest that consumption of diets high in TAC are inversely associated with plasma CRP levels cross-sectionally and dynamically and may contribute to CVD protection.
Assuntos
Antioxidantes/administração & dosagem , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Comportamento Alimentar , Obesidade/sangue , Sobrepeso/sangue , Pós-Menopausa/sangue , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/prevenção & controle , Quimiocina CCL2/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Suplementos Nutricionais , Ingestão de Energia , Feminino , Humanos , Pessoa de Meia-Idade , Avaliação Nutricional , Fatores de Risco , Triglicerídeos/sangueRESUMO
OBJECTIVE: To validate a brief FFQ developed for capturing short-term antioxidant intake in a sample of US college students. DESIGN: A seventy-four-item antioxidant FFQ was developed based on major antioxidant sources in the American diet. The FFQ was validated against 30 d food records (FR) and plasma antioxidant concentrations. The reliability of the FFQ was evaluated by two FFQ administered at a 1-month interval. Settings University of Connecticut, CT, USA. SUBJECTS: Sixty healthy college students. RESULTS: Estimates of dietary antioxidants from the FFQ were moderately to highly correlated with those estimated from the 30 d FR (r = 0·29-0·80; P < 0·05) except for γ-tocopherol and ß-cryptoxanthin. Total antioxidant capacity from diet only or from diet and supplements estimated by the 30 d FR and FFQ were highly correlated (r = 0·67 and 0·71, respectively; P < 0·0001). The FFQ categorized 91 % of participants into the same or adjacent tertiles of antioxidant intake as the 30 d FR. Most dietary carotenoids estimated from the FFQ were correlated with plasma levels (P < 0·05). Correlation coefficients for test-retest reliability ranged from 0·39 to 0·86. More than 94 % of the participants were classified in the same or adjacent tertiles between the two administrations of the FFQ. CONCLUSIONS: The brief FFQ demonstrated reasonable validity for capturing a comprehensive antioxidant intake profile. This FFQ is applicable in epidemiological or clinical studies to capture short-term antioxidant intake or to simply document the variations of antioxidant intake in intervention trials. Cross-validation studies are warranted in other target populations.
Assuntos
Antioxidantes/administração & dosagem , Biomarcadores/sangue , Registros de Dieta , Suplementos Nutricionais , Comportamento Alimentar , Inquéritos e Questionários , Adolescente , Adulto , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/sangue , Índice de Massa Corporal , Carotenoides/administração & dosagem , Carotenoides/sangue , Connecticut , Criptoxantinas , Ingestão de Energia , Feminino , Humanos , Licopeno , Masculino , Reprodutibilidade dos Testes , Xantofilas/administração & dosagem , Xantofilas/sangue , Adulto Jovem , beta Caroteno/administração & dosagem , beta Caroteno/sangue , gama-Tocoferol/administração & dosagem , gama-Tocoferol/sangueRESUMO
OBJECTIVE: To validate an FFQ to assess antioxidant intake in overweight postmenopausal women. DESIGN: A seventy-four-item antioxidant 1-month FFQ was developed based on major antioxidant sources in the American diet. Forty overweight postmenopausal women participated in a 9-month observational study and completed four sets of FFQ and 7 d food record (7dFR) every 3 months. Twelve-hour fasting blood was collected for plasma antioxidant measurement at the first visit. SETTING: Connecticut, USA. SUBJECTS: Forty overweight postmenopausal women. RESULTS: Spearman correlation coefficients of 1-month antioxidant intake estimated from the first set of FFQ and 7dFR ranged from 0·34 to 0·87, except for γ-tocopherol. The proportion of participants categorized into the extremely opposite tertiles averaged 7 %. Significant correlations were observed for diet-plasma vitamin C, α-tocopherol and carotenoids (P < 0·05). No time effect was observed on the dietary antioxidant intakes estimated from four 7dFR and four FFQ. Dietary antioxidants estimated from averaged four 7dFR showed moderate to high correlation with those estimated from averaged four FFQ and from each FFQ collected every 3 months. Bland-Altman plots did not show any systematic bias. Averaged misclassifications were below 10 % between these two instruments. CONCLUSIONS: These findings attested a reasonable validity and a good acceptance of this 1-month FFQ in assessing both short-term and long-term diverse antioxidant intakes in these overweight postmenopausal women. The use of this FFQ in associating antioxidant intake with disease risk needs further investigation.
Assuntos
Antioxidantes/administração & dosagem , Inquéritos sobre Dietas/normas , Dieta , Avaliação Nutricional , Obesidade , Pós-Menopausa , Inquéritos e Questionários/normas , Antioxidantes/metabolismo , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/sangue , Carotenoides/administração & dosagem , Carotenoides/sangue , Connecticut , Comportamento Alimentar , Feminino , Humanos , Pessoa de Meia-Idade , Estado Nutricional , Obesidade/sangue , Pós-Menopausa/sangue , Reprodutibilidade dos Testes , Tocoferóis/administração & dosagem , Tocoferóis/sangueRESUMO
Prostate cancer is the most common noncutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, whereas lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms.
Assuntos
Antioxidantes/administração & dosagem , Dieta , Suplementos Nutricionais , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/prevenção & controle , Ácido Ascórbico/administração & dosagem , Carotenoides/administração & dosagem , Café/química , Humanos , Licopeno , Masculino , Polifenóis/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Selênio/administração & dosagem , Chá/química , Estados Unidos/epidemiologia , alfa-Tocoferol/administração & dosagem , beta Caroteno/administração & dosagem , gama-Tocoferol/administração & dosagemRESUMO
PURPOSE: To investigate the associations of dietary TAC from diet and supplements with serum antioxidant concentrations and serum C-reactive protein (CRP) and plasma total homocysteine (tHcy) in US adults. METHODS: This was a cross-sectional study. Food consumption data, serum antioxidant levels, and serum CRP and Plasma tHcy concentrations of 4,391 US adults aged ≥19 years in the National Health and Nutrition Examination Survey 2001-2002 were analyzed. The USDA flavonoid and proanthocyanidin databases and dietary supplement data as well as antioxidant capacities of 43 antioxidants were also utilized. RESULT: Serum CRP and plasma tHcy concentrations were higher in older adults, smokers, and those with lower non-leisure time physical activity levels (P < 0.05). Energy-adjusted daily total antioxidant capacity (TAC) from diet and supplements was positively associated with serum vitamin E and carotenoid concentrations (P < 0.05). Adjusted odds ratio (OR) for plasma tHcy >13 µmol/L significantly decreased across quartiles of TAC from diet and supplements (Q1 = 2.18 (1.56-2.77); Q2 = 1.30 (1.00-2.07); Q3 = 1.34 (0.84-2.28); Q4 = 1.00; P for linear trend <0.001). A negative trend across quartiles of TAC from diet and supplements was also observed in OR for serum CRP ≥3 mg/L (Q1 = 1.26 (0.97-1.70); Q2 = 1.21 (0.91-1.66); Q3 = 0.97 (0.80-1.24); Q4 = 1.00; P for linear trend <0.05). CONCLUSIONS: These findings indicated that dietary TAC provided an integrated conceptual tool in assessing serum antioxidants and investigating the associations between antioxidant intake and CVD risk. The implicated applicability of dietary TAC needs further validation in prospective cohort studies.
Assuntos
Antioxidantes/administração & dosagem , Proteína C-Reativa/metabolismo , Suplementos Nutricionais , Homocisteína/sangue , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Carotenoides/administração & dosagem , Carotenoides/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Inquéritos Nutricionais , Proantocianidinas/administração & dosagem , Proantocianidinas/sangue , Estados Unidos , Adulto JovemRESUMO
Oxidative stress due to the over-production of reactive oxygen species (ROS) is associated with human skin aging. This study was designed to identify the bioactive phenolics in detoxified Rhus verniciflua Stokes (DRVS) that may protect human skin against oxidative stress. Under oxidative stress caused by H2O2, the 40% (v/v) aqueous methanol extract of DRVS protected human keratinocytes in a dose-dependent manner. The expression of matrix metalloproteinase-1 (MMP-1) was also inhibited by the DRVS extract in human dermal fibroblasts-neonatal cells exposed to ultraviolet A. The major bioactive phenolics of DRVS were tentatively identified by LC/Q-TOF-ESI-MS/MS, and included gallic acid, 2-(ethoxymethoxy)-3-hydroxyphenol, fustin, a fustin isomer, tetragalloyl glucose, pentagalloyl glucose, fisetin, sulfuretin, a sulfuretin isomer, and butein. The results suggest that a DRVS extract may be effective in slowing skin aging through its antioxidative properties and by down-regulating MMP-1 expression. Further studies are needed to examine whether this effect would be mediated by the phenolics identified in this study.
Assuntos
Fibroblastos/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Fenóis/isolamento & purificação , Extratos Vegetais/farmacologia , Toxicodendron/química , Linhagem Celular , Fibroblastos/efeitos da radiação , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/toxicidade , Queratinócitos/efeitos da radiação , Metaloproteinase 1 da Matriz/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Espécies Reativas de Oxigênio , Espectrometria de Massas em Tandem , Raios UltravioletaRESUMO
Nonalcoholic steatohepatitis (NASH) is characterized by oxidative stress and inflammatory responses that exacerbate liver injury. The objective of this study was to determine whether the antioxidant and antiinflammatory activities of green tea extract (GTE) would protect against NASH in a model of diet-induced obesity. Adult Wistar rats were fed a low-fat (LF) diet or high-fat (HF) diet containing no GTE or GTE at 1% or 2% (HF+2GTE) for 8 wk. The HF group had greater (P ≤ 0.05) serum alanine (ALT) and aspartate aminotransferases and hepatic lipids than the LF group. Both GTE groups had lower ALT and hepatic lipid than the HF group. In liver and epididymal adipose, the HF group had lower glutathione as well as greater mRNA and protein expression of TNFα and monocyte chemoattractant protein-1 (MCP-1) and NFκB binding activity than the LF group. Compared to the HF group, the HF+2GTE group had greater glutathione and lower protein and mRNA levels of inflammatory cytokines in both tissues. NFκB binding activities at liver and adipose were also lower, likely by inhibiting the phosphorylation of inhibitor of NFκB. NFκB binding activities in liver and adipose (P ≤ 0.05; r = 0.62 and 0.46, respectively) were correlated with ALT, and hepatic NFκB binding activity was inversely related to liver glutathione (r = -0.35). These results suggest that GTE-mediated improvements in glutathione status are associated with the inhibition of hepatic and adipose inflammatory responses mediated by NFκB, thereby protecting against NASH.
Assuntos
Dieta , Fígado Gorduroso/complicações , NF-kappa B/antagonistas & inibidores , Obesidade/etiologia , Extratos Vegetais/farmacologia , Chá/química , Animais , Sequência de Bases , Citocinas/metabolismo , Primers do DNA , Masculino , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica , Obesidade/complicações , Obesidade/metabolismo , Fosforilação , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Given the importance of dietary antioxidants in reducing the risks of chronic diseases, the present study aimed to estimate the intake of total antioxidant capacity (TAC) from diet and dietary supplements of US adults. We utilised the US Department of Agriculture flavonoid and proanthocyanidin databases, dietary supplement data and food consumption data of 4391 US adults aged 19+ years in the National Health and Nutrition Examination Survey 2001-2. In order to convert the intake data of individual antioxidant compounds to TAC values, the vitamin C equivalent (VCE) of forty-three antioxidant nutrients measured previously was also applied. Daily TAC averaged 503.3 mg VCE/d (approximately 75 % from diet and 25 % from supplements). The energy-adjusted daily TAC level from diet and supplements was higher in women (except for carotenoids), older adults, Caucasian (except for carotenoids), non-alcohol consumers (for vitamin E and proanthocyanidins), subjects with higher income (except for carotenoids) and higher exercise levels than their counterparts (P < 0.05). TAC was positively associated with daily consumption of fruits and fruit juices, vegetables and vegetable products, beverages, wines and teas (P < 0.001). Teas, dietary supplements, and fruits and fruit juices were the major sources of dietary TAC of the US population (28, 25 and 17 %, respectively), while the contribution of vegetables and vegetable products to TAC was minimal ( < 2 %). The present study indicates that antioxidant intake from various diet and supplements contributes to TAC status. TAC levels are different in sociodemographic subgroups of the US population. The relationship between TAC intake and risks of chronic disease warrants further investigation.
Assuntos
Antioxidantes/análise , Dieta , Suplementos Nutricionais , Comportamento Alimentar , Adulto , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas , Antioxidantes/administração & dosagem , Carotenoides/análise , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Proantocianidinas/análise , Grupos Raciais , Fatores Sexuais , Estados Unidos , Vitamina E/análise , População Branca , Adulto JovemRESUMO
OBJECTIVE: To investigate the association of antioxidant intakes from diet and supplements with elevated blood C-reactive protein (CRP) and homocysteine (Hcy) concentrations. DESIGN: A cross-sectional study. The main exposures were vitamins C and E, carotene, flavonoid and Se intakes from diet and supplements. Elevated blood CRP and Hcy concentrations were the outcome measures. SETTING: The US population and its subgroups. SUBJECTS: We included 8335 US adults aged ≥19 years from the National Health and Nutrition Examination Survey 1999-2002. RESULTS: In this US population, the mean serum CRP concentration was 4·14 (95 % CI 3·91, 4·37) mg/l. Intakes of vitamins C and E and carotene were inversely associated with the probability of having serum CRP concentrations >3 mg/l in multivariate logistic regression models. Flavonoid and Se intakes were not associated with the odds of elevated serum CRP concentrations. The mean plasma Hcy concentration was 8·61 (95 % CI 8·48, 8·74) µmol/l. Intakes of vitamins C, E, carotenes and Se were inversely associated with the odds of plasma Hcy concentrations >13 µmol/l after adjusting for covariates. Flavonoid intake was not associated with the chance of elevated plasma Hcy concentrations. CONCLUSIONS: These results suggest that high antioxidant intake is associated with lower blood concentrations of CRP and Hcy. These inverse associations may be among the potential mechanisms for the beneficial effect of antioxidant intake on CVD risk mediators in observational studies.
Assuntos
Antioxidantes/administração & dosagem , Proteína C-Reativa/análise , Dieta , Suplementos Nutricionais , Homocisteína/sangue , Adulto , Ácido Ascórbico/administração & dosagem , Proteína C-Reativa/metabolismo , Carotenoides/administração & dosagem , Estudos Transversais , Feminino , Flavonoides/administração & dosagem , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Inquéritos Nutricionais , Selênio/administração & dosagem , Estados Unidos , Vitamina E/administração & dosagem , Vitaminas/administração & dosagemRESUMO
The importance of antioxidants in reducing risks of chronic diseases has been well established; however, antioxidant intakes by a free-living population have not yet been estimated adequately. In this study, we aimed to estimate total antioxidant intakes from diets and supplement sources in the U.S. population. The USDA Flavonoid Database, food consumption data, and dietary supplement use data of 8809 U.S. adults aged >/=19 y in NHANES 1999-2000 and 2001-2002 were used in this study. Daily total antioxidant intake was 208 mg vitamin C (46 and 54% from diets and supplements, respectively), 20 mg alpha-tocopherol (36 and 64), 223 mug retinol activity equivalents carotenes (86 and 14), 122 mug selenium (89 and 11), and 210 mg flavonoids (98 and 2). Antioxidant intakes differed among sociodemographic subgroups and lifestyle behaviors. Energy-adjusted dietary antioxidant intakes were higher in women, older adults, Caucasians, nonconsumers of alcohol (only for vitamin C and carotenes), nonsmokers (only for vitamin C, vitamin E, and carotenes), and in those with a higher income and exercise level (except for flavonoids) than in their counterparts (P < 0.05). Consumption of fruits, vegetables, and whole grains may be a good strategy to increase antioxidant intake. The possible association between antioxidant intake and the prevalence of chronic diseases should be investigated further.
Assuntos
Antioxidantes/administração & dosagem , Dieta/estatística & dados numéricos , Suplementos Nutricionais/estatística & dados numéricos , Adulto , Idoso , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores Socioeconômicos , Estados Unidos , Adulto JovemRESUMO
Estimation of total antioxidant intake is the first step to investigate the protective effects of antioxidants on oxidative stress-mediated disease. The present study was designed to develop an algorithm to estimate total antioxidant capacity (TAC) of the US diet. TAC of individual antioxidants and 50 popular antioxidant-rich food items in the US diet were determined by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assay and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Theoretical TAC of foods was calculated as the sum of individual antioxidant capacities of compounds. The top 10 TAC food items in the US diet according to standard serving size were blueberry > plum > green tea > strawberry > green tea (decaffeinated) > red wine > grape juice > black tea > cherry > grape. Major contributors to TAC were the total phenolic content (r = 0.952, P < 0.001) and flavonoid content (r = 0.827, P < 0.001) of 50 foods. Theoretical TAC was positively correlated to experimental TAC of 50 foods determined by the ABTS assay (r = 0.833, P < 0.001) and the DPPH assay (r = 0.696, P < 0.001), and to TAC from the USDA database for the oxygen radical absorbance capacity (r = 0.484, P = 0.001, n = 44). The TAC database of the US diet has been established and validated. In future studies, TAC of the US diet can be linked to biomarkers of chronic disease.
Assuntos
Algoritmos , Antioxidantes/farmacologia , Bases de Dados Factuais , Dieta , Flavonoides/farmacologia , Análise de Alimentos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Benzotiazóis/metabolismo , Compostos de Bifenilo/metabolismo , Humanos , Picratos/metabolismo , Polifenóis , Espécies Reativas de Oxigênio/metabolismo , Ácidos Sulfônicos/metabolismo , Estados Unidos , United States Department of AgricultureRESUMO
Recent studies have suggested that blackcurrant (BC) anthocyanins have promising health benefits, possibly through regulating gut microbiome. Three- and eighteen-month old female mice were fed standard mouse diets for 4 months, each with or without BC (1% w/w) supplementation (n = 3 in each treatment group, 12 in total). We then assessed gut microbiome profiles using 16S sequencing of their feces. Old mice had a less diverse microbiome community compared to young mice and there was a remarkable age-related difference in microbiome composition in the beta diversity analysis. BC supplementation did not significantly affect alpha or beta diversity. The relative abundance of several phyla, including Firmicutes, Bacteroidetes, Proteobacteria and Tenericutes, was lower in old mice. BC downregulated Firmicutes abundance in young mice and upregulated Bacteroidetes in both age groups, leading to a decreased Firmicutes/Bacteroidetes ratio. There were age-specific differences in the effect of BC supplementation on the microbiome. Twenty-four operational taxonomic units showed a significant interaction between age and BC supplementation (p < 0.01), which suggests that the ecosystem and the host health status affect the functions and efficiency of BC intake. These results indicate that BC supplementation favorably modulates gut microbiome, but there are distinct age-specific differences. Studies with human hosts are needed to better understand BC's regulatory effects on the gut microbiome.
Assuntos
Fatores Etários , Antocianinas/farmacologia , Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , Ribes/química , Envelhecimento/metabolismo , Animais , Ecossistema , Feminino , Nível de Saúde , Camundongos , FilogeniaRESUMO
The objective of this study was to determine whether green tea (GT) inhibits the expression of genes regulating hepatic lipogenesis and intestinal lipid transport in fructose-fed ovariectomized (OX) rats. OX rats were assigned to: 1) a control group (S) fed the AIN-93G diet with corn starch as the major carbohydrate source; 2) another control group (F) fed the same diet but containing fructose at 60% as the major carbohydrate source; 3) a group fed the F diet but containing 0.5% GT; and 4) a group fed the F diet containing 1% GT. At 6 wk, plasma and liver triglyceride (TG) and cholesterol and expression of liver sterol regulatory element-binding protein-1c (SREBP-1c) and selected genes involved in lipogenesis and lipid transport were measured. Fructose elevated plasma TG and cholesterol compared with the S group. GT at 0.5 and 1.0% markedly lowered plasma and liver TG. Fructose increased the expression of SREBP-1c, fatty acid synthase, and stearoyl-CoA desaturase 1 mRNA in the liver, whereas GT decreased the expression of these lipogenic genes. Similarly, fructose increased the abundance of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase mRNA, whereas GT significantly decreased its expression. GT did not alter the expression of scavenger receptor class B, type 1, microsomal TG transfer protein, and apobec 1 in the liver and intestine. The results suggest that the lipid-lowering effect of GT is mediated partly by its inhibition of hepatic lipogenesis involving SREBP-1c and its responsive genes without affecting lipoprotein assembly.
Assuntos
Frutose/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Chá/química , Triglicerídeos/metabolismo , Ração Animal , Animais , Glicemia/metabolismo , Cor , Feminino , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
Consumption of green tea may reduce body weight gain. Although many disorders are related to obesity, bone mass is positively correlated with body mass. Therefore, our purpose in this study was to determine the effects of green tea extract (GTE) on bone mass and architecture in rapidly growing lean [C57BL/6 wild type (WT)] and genetically obese, leptin-deficient (ob/ob) male mice. Five-week-old lean and ob/ob mice were assigned to diets containing GTE at 0, 1, or 2% for 6 wk. Femoral and lumbar vertebral bone volume and architecture were evaluated by micro-computed tomography (muCT). Following muCT analysis, femora were ashed to determine bone mineral content and density. Compared with WT mice, ob/ob mice had shorter femora (P < 0.001), lower femoral bone volume (P < 0.001), and lower femoral bone mineral content (P < 0.001), but higher cancellous bone volume in lumbar vertebrae (P < 001). Neither genotype nor treatment affected femoral bone mineral density, indicating normal mineralization. GTE consumption resulted in lower femur length, volume, mineral content, cortical volume, and cortical thickness (P < 0.001), as well as lower cancellous bone volume/tissue volume (P < 0.008) and trabecular thickness (P < 0.004) in lumbar vertebrae. The results indicate that leptin is not essential for the reduced gains in body weight and bone mass due to GTE in growing mice and suggest that consumption of large quantities of green tea may reduce the rate of bone accumulation during growth.