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1.
Br J Nutr ; 113(6): 953-62, 2015 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-25772032

RESUMO

New technologies are promising for the use of short-term instruments for dietary data collection; however, innovative tools should be validated against objective biomarkers. The aim of the present study was to investigate the validity of a Web-based, self-administered dietary record (DR) tool using protein, K and Na intakes against 24 h urinary biomarkers (24 h U). Of the total participants, 199 adult volunteers (104 men and 95 women, mean age 50·5 (23-83 years)) of the NutriNet-Santé Study were included in the protocol. They completed three non-consecutive-day DR and two 24 h U on the first and third DR days. Relative differences between reported (DR) and measured (24 h U) intakes were calculated from the log ratio (DR/24 h U) for protein, K and Na intakes: -14·4,+2·6 and -2·1 % for men; and -13·9, -3·7 and -8·3 % for women, respectively. The correlations between reported and true intakes were 0·61, 0·78 and 0·47 for men and 0·64, 0·42 and 0·37 for women for protein, K and Na, respectively. Attenuation factors, that represent attenuation of the true diet-disease relationship due to measurement error (a value closer to 1 indicating lower attenuation), ranged from 0·23 (Na, women) to 0·60 (K, men). We showed that the Web-based DR tool used in the NutriNet-Santé cohort study performs well in estimating protein and K intakes and fairly well in estimating Na intake. Furthermore, three non-consecutive-day DR appear to be valid for estimating usual intakes of protein and K, although caution is advised regarding the generalisability of these findings to other nutrients and general population.


Assuntos
Dieta , Proteínas Alimentares/administração & dosagem , Potássio na Dieta/administração & dosagem , Sódio na Dieta/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Estudos de Coortes , Dieta/efeitos adversos , Registros de Dieta , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Nitrogênio/urina , Avaliação Nutricional , Paris , Potássio/urina , Autorrelato , Sódio/urina , Adulto Jovem
2.
Int J Food Sci Nutr ; 66(4): 391-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25812156

RESUMO

The main aim of this study was to compare the effects of two wheat aleurone (WA) fractions on circulating n-3 fatty acids in rats. We demonstrated that only the fraction able to induce the highest urinary excretion of polyphenol metabolites (>1µmol) resulted in a significant increase in plasma level of Eicosapentanoic acid (+22%, p < 0.05). While other constituents of whole wheat can be involved in this response, our data suggest that cereals containing high levels of phenolic compounds can increase blood n-3 without affecting n-6 fatty acids. Further studies are required to confirm this hypothesis and explore the underlying biological mechanisms.


Assuntos
Ácidos Graxos Ômega-3/sangue , Triticum/metabolismo , Animais , Grão Comestível/metabolismo , Masculino , Ratos , Ratos Wistar
3.
Transfus Clin Biol ; 30(4): 410-416, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37451610

RESUMO

BACKGROUND: Despite major demographic changes, several decisions and initiatives, among which Patient Blood Management, have led to a significant reduction in the transfusion of packed red blood cells (RBCs) in Belgium, as it has been observed in many countries. Unfortunately, not all blood groups were proportionately impacted and shortage in O D-negative RBCs is regularly or chronically observed. The goal of this study was to examine how to optimize the use and the supply of O D-negative blood in our academic hospital. METHODOLOGY: All blood transfusions performed at Cliniques universitaires Saint-Luc between January 1, 2019 and December 31, 2021 were reviewed. The blood group of the patients was compared with the blood group of the RBCs actually supplied and transfused. RESULTS: 49.823 RBCs transfusions were analyzed. The patients' needs didn't reflect those of a Caucasian population, with an increase of O (47.9%) and B (10.3%) for the ABO blood group, and a quite high proportion of R0r (8.6%) for the Rh blood group. Only two thirds of O D-negative RBCs were transfused to O rr or R0r patients. CONCLUSION: The application of PBM and the ethnic imbalance between blood donor and patient populations are two important risk factors for chronic shortages of O D-negative blood. To adapt blood component resources, it is essential to have a complete picture of the real needs of patients according to their blood group profile. Blood donor centers must adapt to the evolving needs of hospitals in order to plan future supplies in a "pull-flow" approach.


Assuntos
Transfusão de Sangue , Eritrócitos , Humanos , Transfusão de Eritrócitos/efeitos adversos , Sistema ABO de Grupos Sanguíneos , Sistema do Grupo Sanguíneo Rh-Hr
4.
Nutrients ; 14(14)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35889904

RESUMO

BACKGROUND: Long-chain omega-3 and omega-6 fatty acids (n-3, n-6 FAs) may modulate inflammation and affect the risk of developing rheumatoid arthritis (RA). However, whether n-3/n-6 FA status affects RA after disease onset is unknown. This study aimed to assess whether FA profiles are independently associated with disease activity in a large prospective cohort of patients with early RA. METHODS: Baseline serum FAs were quantified in 669 patients in the ESPOIR cohort. Principal component analysis identified three serum FA patterns that were rich in n-7-9, n-3 and n-6 FAs (patterns ω7-9, ω3 and ω6), respectively. The association of pattern tertiles with baseline variables and 6-month disease activity was tested using multivariable logistic regression. RESULTS: Pattern ω3 was associated with low baseline and pattern ω6 with high baseline C-reactive protein level and disease activity. Both patterns ω3 and ω6 were associated with reduced odds of active disease after 6 months of follow-up (pattern ω3: odds ratio, tertile three vs. one, 0.49 [95% CI 0.25 to 0.97] and pattern ω6: 0.51 [0.28 to 0.95]; p = 0.04 and 0.03, respectively). CONCLUSIONS: In a cohort of early RA patients, a serum lipid profile rich in n-3 FAs was independently associated with persistently reduced disease activity between baseline and 6-month follow-up. An n-6 FA profile was also associated with lower 6-month disease activity.


Assuntos
Artrite Reumatoide , Ácidos Graxos Ômega-3 , Estudos de Coortes , Ácidos Graxos/metabolismo , Humanos , Estudos Prospectivos
5.
J Nutr ; 141(1): 37-41, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21068183

RESUMO

Flavonoids probably contribute to the health benefits associated with the consumption of fruit and vegetables. However, the mechanisms by which they exert their effects are not fully elucidated. PUFA of the (n-3) series also have health benefits. Epidemiological and clinical studies have suggested that wine flavonoids may interact with the metabolism of (n-3) PUFA and increase their blood and cell levels. The present studies in rats were designed to assess whether flavonoids actually increase plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main very long-chain (n-3) PUFA. Rats were fed a corn-derived anthocyanin (ACN)-rich (ACN-rich) or ACN-free diet with constant intakes of plant and marine (n-3) PUFA for 8 wk (Expt. 1). Plasma fatty acids were measured by GC. The ACN-rich diet contained ~0.24 ± 0.01 mg of ACN/g pellets. There were no significant differences between groups in the main saturated, monounsaturated, and (n-6) fatty acids. In contrast, plasma EPA and DHA were greater in the ACN-rich diet group than in the ACN-free diet group (P < 0.05). We obtained similar results in 2 subsequent experiments in which rats were administered palm oil (80 µL/d) and consumed the ACN-rich or ACN-free diet (Expt. 2) or were supplemented with fish oil (60 mg/d, providing 35 mg DHA and 12 mg EPA) and consumed the ACN-rich or ACN-free diet (Expt. 3). In both experiments, plasma EPA and DHA were significantly greater in the ACN-rich diet group. These studies demonstrate that the consumption of flavonoids increases plasma very long-chain (n-3) PUFA levels. These data confirm previous clinical and epidemiological studies and provide new insights into the health benefits of flavonoids.


Assuntos
Antocianinas/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Animais , Antocianinas/análise , Peso Corporal , Ácidos Docosa-Hexaenoicos/sangue , Ingestão de Alimentos , Ácido Eicosapentaenoico/sangue , Lipídeos/sangue , Masculino , Ratos , Ratos Wistar
6.
Anal Biochem ; 401(1): 7-14, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20175981

RESUMO

Plasma vitamin K1 (phylloquinone) determination is commonly used for the diagnosis of vitamin K deficiency in patients suffering from lipid malabsorption. Moreover, current evidence that adequate vitamin K intake, and correspondingly adequate plasma vitamin K1 concentration, could also be of importance in relation to bone and brain diseases emphasizes the need to improve the current analytical methods. We developed a liquid chromatography coupled to tandem mass spectrometry method using a stable isotope ring-D4-labeled internal standard of vitamin K1 and operating in the multiple reaction monitoring mode by the selection of a precursor and product ions. The atmospheric pressure chemical ionization (APCI) method was shown to be more sensitive than electrospray ionization. After a single-step extraction with cyclohexane, chromatographic separation was performed on a C18 column with an isocratic mobile phase. The linearity was up to 5400ng/L, and the limit of detection was 14ng/L. Intra- and interrun precision were 2.4% and 8.3%, respectively, for the lower limit of the reference range. Recovery was better than 98%. The method is simple and reliable, allowing accurate vitamin K1 measurement in plasma samples from healthy subjects and patients suffering from vitamin K deficiency.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Vitamina K 1/sangue , Cicloexanos/química , Humanos , Marcação por Isótopo , Vitamina K 1/isolamento & purificação , Deficiência de Vitamina K/diagnóstico
7.
Drug Chem Toxicol ; 32(3): 258-67, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19538023

RESUMO

Antioxidant activity of isorhamnetin 3-O neohesperidoside (I3ON), isolated from the leaves of Acacia salicina, was determined by the ability of this compound to inhibit lipid peroxidation and to protect against hydroxyl radical-induced DNA damage in pKS plasmid DNA and Escherichia coli cultures. Antigenotoxic activity was assessed by using the comet assay. The IC(50) value of the inhibitory activity toward lipid peroxidation by I3ON is 0.6 mM. This compound was also able to protect against hydroxyl radical-induced DNA damage in pKS plasmid DNA. Moreover, this compound induced an inhibitory activity toward H2O2-induced genotoxicity. The protective effect exhibited by this molecule was also determined by analysis of gene expression as a response to an oxidative stress, using a cDNA microarray. Transcription of several genes related to the antioxidant system (HMOX2 and TXNL) and to the DNA repair pathway (XPC, POLD1, POLD2, PCNA, DDIT3, APEX, and LIG4) were upregulated after incubation with I3ON. Taken together, these observations provide evidence that the I3ON, isolated from the leaves of A. salicina, is able to protect cells against oxidative stress.


Assuntos
Acacia/química , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaio Cometa , Dano ao DNA , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Flavonóis/farmacologia , Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/toxicidade , Radical Hidroxila/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Oxidantes/toxicidade , Estresse Oxidativo/genética , Folhas de Planta/química , Plasmídeos/efeitos dos fármacos , Plasmídeos/genética , Regulação para Cima/efeitos dos fármacos
8.
Br J Nutr ; 100(6): 1237-44, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18445308

RESUMO

Moderate ethanol drinking (ED) and n-3 fatty acids have both been associated with low cardiac mortality. However, there are few data evaluating the interactions of ED with n-3. We recently reported that moderate ED results in increased n-3 in cardiac patients. The main aim of the present study was, through a well-controlled experimental model, to confirm that chronic ED actually results in increased n-3. Secondary aims were to examine the effects of chronic ED on cardiac mitochondria, cardiac function and experimental myocardial infarction. We studied the fatty acid profiles of plasma, cell membranes and cardiac mitochondria phospholipids in a rat model of chronic ED. In plasma and cell membranes, ED actually resulted in higher n-3 (P = 0.005). In mitochondria phospholipids of ED rats, n-3 were also increased (P < 0.05) but quite modestly. Cardiac mitochondrial function and left ventricular function were not significantly different in ED and control rats, while infarct size after 30 min ischaemia and reperfusion was smaller (P < 0.0001) in ED rats. This is the first animal study confirming interaction of alcohol drinking with n-3. We found no harmful effect of chronic ED on the heart in that model but a significant cardioprotection. Further studies are warranted to investigate the mechanisms by which moderate ED alters the metabolism of n-3 and whether n-3 are the mediators of the ED-induced cardioprotection.


Assuntos
Consumo de Bebidas Alcoólicas/sangue , Ácidos Graxos Ômega-3/sangue , Animais , Membrana Celular/metabolismo , Modelos Animais de Doenças , Etanol/administração & dosagem , Etanol/farmacologia , Ácidos Graxos/sangue , Lipídeos/sangue , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/fisiologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fosfolipídeos/metabolismo , Ratos , Ratos Wistar , Função Ventricular Esquerda/efeitos dos fármacos
9.
Toxicol In Vitro ; 22(7): 1671-80, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18662769

RESUMO

Zearalenone (Zen) is a fusarial mycotoxin commonly found in several food commodities worldwide. It is frequently implicated in reproductive disorders and exerts several genotoxic effects in vivo and in vitro. In response to DNA damage, cells may undergo an intricate network of different pathways including apoptosis. Meanwhile, data regarding the induction of apoptosis after Zen exposure are limited. Thus, the aim of this study was to demonstrate whether Zen-induced DNA damage can lead to apoptosis as a stress response and which pathways are undertaken. Our results clearly show that Zen reduces cell proliferation in HepG2 cells in a dose-dependent manner as attested by the MTT assay (IC50%, 100microM). The analysis of propidum iodide uptake has shown that the amount of necrotic cells was about 6% among 55% of dead cells (at 120microM of Zen). The involvement of apoptosis as a major cause of Zen-induced cell death was further confirmed but results of caspase-3 activity showed a Zen-dose dependant increase. Furthermore, results of microarrays analysis have shown that Zen induced an upregulation of ATM and p53 genes family. ATM pathway responds primarily to DNA double-strand breaks and has been involved in the activation and stabilization of p53. The activation of p53 was accompanied by an upregulation of GADD45 to arrest the cell cycle and to allow the repair mechanisms to take place. In addition, results of genes profiling as well as western-blotting analysis showed that Zen increased the ratio of pro-apoptotic factors/anti-apoptotic factors which led to the loss of mitochondrial potential, Bax translocation and cytochrome c release. Once released, cytochome c activates caspase 9 which in turn activates caspase-3 and enhances apoptosis. In summary, these data suggested that Zen induced apoptosis in a dose-dependent manner in HepG2 cells via a p53-dependent mitochondrial pathway.


Assuntos
Apoptose/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Proteína Supressora de Tumor p53/efeitos dos fármacos , Zearalenona/toxicidade , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/efeitos dos fármacos , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromos c/efeitos dos fármacos , Citocromos c/metabolismo , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Zearalenona/administração & dosagem
10.
Toxicol In Vitro ; 22(5): 1264-72, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18515041

RESUMO

The total oligomers flavonoids (TOF), chloroform, petroleum ether and aqueous extracts from Acacia salicina, were investigated for the antioxidative, cytotoxic, antimutagenic and antigenotoxic activities. The viability of K562 cells were affected by all extracts after 48 h exposure. Our results showed that A. salicina extracts have antigenotoxic and/or antimutagenic activities. TOF and chloroform extracts exhibit antioxidant properties, expressed by the capacity of these extracts to inhibit xanthine oxidase activity. To further explore the mechanism of action of A. salicina extracts, we characterized expression profiles of genes involved in antioxidant protection and DNA repair in the human lymphoblastic cell line K562 exposed to H2O2. Transcription of several genes related to the thioredoxin antioxidant system and to the DNA base-excision repair pathway was up-regulated after incubation with chloroform, TOF and petroleum ether extracts. Moreover genes involved in the nucleotide-excision repair pathway and genes coding for catalase and Mn-superoxide-dismutase, two important antioxidant enzymes, were induced after incubation with the chloroform extract. Taken together, these observations provide evidence that the chloroform and TOF extracts of A. salicina leaves contain bioactive compounds that are able to protect cells against the consequences of an oxidative stress.


Assuntos
Acacia/química , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Medicina Tradicional , Oxidantes/farmacologia , Animais , Linhagem Celular Tumoral , Ensaio Cometa , DNA/efeitos dos fármacos , Combinação de Medicamentos , Flavonoides/química , Formazans/metabolismo , Perfilação da Expressão Gênica , Genes Bacterianos/efeitos dos fármacos , Humanos , Células K562/efeitos dos fármacos , Células K562/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Extratos Vegetais/farmacologia , Ratos , Proteína S9 Ribossômica , Proteínas Ribossômicas/efeitos dos fármacos , Proteínas Ribossômicas/metabolismo , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Sais de Tetrazólio/metabolismo
12.
Cancers (Basel) ; 11(1)2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30583471

RESUMO

Glioblastoma multiform (GBM) tumors are very heterogeneous, organized in a hierarchical pattern, including cancer stem cells (CSC), and are responsible for development, maintenance, and cancer relapse. Therefore, it is relevant to establish new GBM cell lines with CSC characteristics to develop new treatments. A new human GBM cell line, named R2J, was established from the cerebro-spinal fluid (CSF) of a patient affected by GBM with leptomeningeal metastasis. R2J cells exhibits an abnormal karyotype and form self-renewable spheres in a serum-free medium. Original tumor, R2J, cultured in monolayer (2D) and in spheres showed a persistence expression of CD44, CD56 (except in monolayer), EGFR, Ki67, Nestin, and vimentin. The R2J cell line is tumorigenic and possesses CSC properties. We tested in vitro the anticancer effects of sodium selenite (SS) compared to temozolomide TMZ. SS was absorbed by R2J cells, was cytotoxic, induced an oxidative stress, and arrested cell growth in G2M before inducing both necrosis and apoptosis via caspase-3. SS also modified dimethyl-histone-3-lysine-9 (H3K9m2) levels and decreased histone deacetylase (HDAC) activity, suggesting anti-invasiveness potential. This study highlights the value of this new GBM cell line for preclinical modeling of clinically relevant, patient specific GBM and opens a therapeutic window to test SS to target resistant and recurrent GBM.

13.
Free Radic Res ; 41(1): 25-37, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17164176

RESUMO

Phytoprostanes (PP) are autoxidation products of alpha-linolenate that are present in all plant tissues. Several classes of PP with a prostaglandin (PG) F1-, E1-, A1- and B1-like structure were identified and quantified by gas chromatography-mass spectrometry in vegetable oils and parenteral nutrition (intralipid). High levels of PP (0.09 up to 99 mg/l) were found even in apparently fresh vegetable oils. After oral consumption of olive or soybean oil, PPF1 were absorbed, found to circulate in plasma in conjugated form and excreted in free form into urine. Evidence is emerging that certain PP, such as the PPE1, may modulate the function of immune cells in a PG-like fashion. Here, we show that PPA1- and deoxy-PPJ1 display potent anti-inflammatory and apoptosis inducing activities similar to PGA1 and deoxy-PGJ2. Results of this study indicate that PP are novel, biologically active lipids in plant nutrition.


Assuntos
Ciclopentanos/farmacologia , Ácidos Graxos Insaturados/farmacologia , Óleos de Plantas/química , Óleos de Plantas/metabolismo , Adolescente , Adulto , Animais , Apoptose/efeitos dos fármacos , Ciclopentanos/química , Ciclopentanos/metabolismo , Emulsões Gordurosas Intravenosas/química , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/metabolismo , Humanos , Células Jurkat , Masculino , Espectrometria de Massas , Camundongos , Óxido Nítrico/metabolismo , Nutrição Parenteral
14.
Chem Biol Interact ; 168(3): 171-83, 2007 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-17512922

RESUMO

The ability of three Rhamnus alaternus leaves extracts on antigenotoxic and gene expression level effects was respectively investigated in a bacterial assay system, i.e. the SOS chromotest with Escherichia coli PQ37 and in human K562 lymphoblast cell line. Total oligomers flavonoids (TOF) enriched, methanol and ethyl acetate extracts were prepared from powdered R. alaternus leaves and characterized quantitatively for the presence of polyphenolic compounds. We explored the response to oxidative stress using the transcriptional profile of genes in K562 cells stressed with H2O2 after incubation with plant extracts. For this purpose, we used a cDNA microarrays containing 82 genes related to cell defense, essentially represented by antioxidant and DNA repair genes. Analysis revealed that SOD1, AOE 372, TXN genes involved in the antioxidant defense system and XPC, LIG4, POLD2, PCNA genes implied in the DNA repair system were among the most expressed ones in the presence of the tested extracts. These results were in accordance with those obtained when we tested the antigenotoxic and antioxidant effects of the same extracts with, respectively the SOS chromotest and the xanthine/xanthine oxidase enzymatic assay system. The effect of the tested extracts on SOS response induced by both Aflatoxin B1 (AFB1: 10 microg/assay) and nifuroxazide (20 microg/assay) showed that the TOF extract exhibited the highest antimutagenic level towards the indirect mutagen AFB1. Whereas ethyl acetate extract showed the highest antimutagenic effect towards the direct mutagen, nifuroxazide. None of the tested extracts induced mutagenic activity. However all the tested extracts exhibited xanthine oxidase inhibiting and superoxide anions scavenging effects. R. alaternus extracts contain compounds with significant antioxidant and antigenotoxic activities. These compounds modulate gene expression as detected by using cDNA arrays.


Assuntos
Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Fenóis/farmacologia , Rhamnus/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Flavonoides/química , Sequestradores de Radicais Livres/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Humanos , Testes de Mutagenicidade , Análise de Sequência com Séries de Oligonucleotídeos , Fenóis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , RNA/genética , RNA/metabolismo , Superóxidos/metabolismo , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
15.
Chem Biol Interact ; 165(1): 1-13, 2007 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-17129579

RESUMO

In vitro antioxidant and antimutagenic activities of two polyphenols isolated from the fruits of Pistacia lentiscus was assessed. Antioxidant activity was determined by the ability of each compound to scavenge the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH*), to inhibit xanthine oxidase and to inhibit the lipid peroxidation induced by H(2)O(2) in K562 cell line. Antimutagenic activity was assayed with SOS chromotest using Escherichia coli PQ37 as tester strain and Comet assay using K562 cell line. 1,2,3,4,6-Pentagalloylglucose was found to be more effective to scavenge DPPH* radical and protect against lipid peroxidation. Moreover, these two compounds induced an inhibitory activity against nifuroxazide and aflatoxin B1 mutagenicity. The protective effect exhibited by these molecules was also determined by analysis of gene expression as response to an oxidative stress. For this purpose, we used a cDNA-microarray containing 82 genes related to cell defense, essentially represented by antioxidant and DNA repair proteins. We found that 1,2,3,4,6-pentagalloylglucose induced a decrease in the expression of 11 transcripts related to antioxidant enzymes family (GPX1, TXN, AOE372, SHC1 and SEPW1) and DNA repair (POLD1, APEX, POLD2, MPG, PARP and XRCC5). The use of Gallic acid, induced expression of TXN, TXNRD1, AOE372, GSS (antioxidant enzymes) and LIG4, POLD2, MPG, GADD45A, PCNA, RPA2, DDIT3, HMOX2, XPA, TDG, ERCC1 and GTF2H1 (DNA repair) as well as the repression of GPX1, SEPW1, POLD1 and SHC1 gene expression.


Assuntos
Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Ácido Gálico/farmacologia , Taninos Hidrolisáveis/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Pistacia/química , Aflatoxina B1/antagonistas & inibidores , Ensaio Cometa , Relação Dose-Resposta a Droga , Escherichia coli/genética , Sequestradores de Radicais Livres/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Hidroxibenzoatos/antagonistas & inibidores , Células K562 , Testes de Mutagenicidade , Nitrofuranos/antagonistas & inibidores , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Xantina Oxidase/antagonistas & inibidores
16.
J Trace Elem Med Biol ; 44: 161-176, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28965572

RESUMO

Glioblastoma (GBM) is the most common type of primary tumor of the central nervous system with a poor prognosis, needing the development of new therapeutic drugs. Few studies focused on sodium selenite (SS) effects in cancer cells cultured as multicellular tumor spheroids (MCTS or 3D) closer to in vivo tumor. We investigated SS anticancer effects in three human GBM cell lines cultured in 3D: LN229, U87 (O(6)-methyguanine-DNA-methyltransferase (MGMT) negative) and T98G (MGMT positive). SS absorption was evaluated and the cytotoxicity of SS and temozolomide (TMZ), the standard drug used against GBM, were compared. SS impacts on proliferation, cell death, and invasiveness were evaluated as well as epigenetic modifications by focusing on histone deacetylase (HDAC) activity and dimethyl-histone-3-lysine-9 methylation (H3K9m2), after 24h to 72h SS exposition. SS was absorbed by spheroids and was more cytotoxic than TMZ (i.e., for LN229, the IC50 was 38 fold-more elevated for TMZ than SS, at 72h). SS induced a cell cycle arrest in the S phase and apoptosis via caspase-3. SS decreased carbonic anhydrase-9 (CA9) expression, invasion on a Matrigel matrix and modulated E- and N-Cadherin transcript expressions. SS decreased HDAC activity and modulated H3K9m2 levels. 3D model provides a relevant strategy to screen new drugs and SS is a promising drug against GBM that should now be tested in GBM animal models.


Assuntos
Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Selenito de Sódio/uso terapêutico , Esferoides Celulares/patologia , Antígenos de Neoplasias/metabolismo , Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Anidrase Carbônica IX/metabolismo , Caspase 3/metabolismo , Agregação Celular/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Humanos , Necrose , Invasividade Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Selenito de Sódio/farmacologia , Esferoides Celulares/efeitos dos fármacos
17.
Sci Rep ; 7: 40162, 2017 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-28071699

RESUMO

As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers' health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats. The intake of plant n-3 alpha-linolenic acid and WR results in a sort of fatty fish-like effect, demonstrating that the n-3 LCFA levels in blood and tissues could be increased without eating marine foods, and therefore without promoting unsustainable overfishing, and without damaging marine ecology.


Assuntos
Dieta/métodos , Ácidos Graxos Ômega-3/metabolismo , Polifenóis/metabolismo , Secale/química , Animais , Ácidos Graxos Ômega-3/sangue , Microbioma Gastrointestinal , Fígado/metabolismo , Ratos
18.
Anticancer Agents Med Chem ; 16(4): 490-500, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26286659

RESUMO

AIMS: Selenium (Se) is an essential trace element for human health which also has antitumor properties. Little is known about its effects on brain tumor cells (BTC). The aim of this study was to investigate the anticancer effects of sodium selenite (SS) including histone deacetylase (HDAC) activity in three human glioblastoma (GBM) cell lines (LN229, T98G and U87). MATERIALS & METHODS: LN229, T98G and U87 GBM cell lines were treated with variable doses of SS for time varying from 24 to 72h. HDAC activity, cell proliferation, toxicity, cell death process, caspase-3 and MMP2 activities and Se absorption were evaluated. RESULTS: SS modulated all the parameters tested in a dose- and time-dependent manner. We found that SS decreased HDAC activity, blocked cell proliferation and cell cycle at the G2 phase, triggered an apoptotic cell death process caspase-3-dependent and reduced MMP2 activities. All these effects were performed whereas SS was weakly absorbed (<2%). CONCLUSIONS: SS decreasing HDAC activity exhibited interesting antitumor properties in GBM cells which may be taken into account in the novel strategies for achieving tumor growth inhibition and cytotoxicity. Epigenetic modifications induced by SS should be evaluated in further studies.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Glioblastoma/enzimologia , Glioblastoma/patologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Selenito de Sódio/farmacologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioblastoma/tratamento farmacológico , Humanos , Relação Estrutura-Atividade , Células Tumorais Cultivadas
19.
J Acad Nutr Diet ; 116(3): 427-438.e5, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26522988

RESUMO

BACKGROUND: It is of major importance to measure the validity of self-reported dietary intake using web-based instruments before applying them in large-scale studies. OBJECTIVE: This study aimed to validate self-reported intake of fish, fruit and vegetables, and selected micronutrient intakes assessed by a web-based self-administered dietary record tool used in the NutriNet-Santé prospective cohort study, against the following concentration biomarkers: plasma beta carotene, vitamin C, and n-3 polyunsaturated fatty acids. PARTICIPANTS/SETTING: One hundred ninety-eight adult volunteers (103 men and 95 women, mean age=50.5 years) were included in the protocol: they completed 3 nonconsecutive-day dietary records and two blood samples were drawn 3 weeks apart. The study was conducted in the area of Paris, France, between October 2012 and May 2013. MAIN OUTCOME MEASURES: Reported fish, fruit and vegetables, and selected micronutrient intakes and plasma beta carotene, vitamin C, and n-3 polyunsaturated fatty acid levels were compared. STATISTICAL ANALYSES: Simple and adjusted Spearman's rank correlation coefficients were estimated after de-attenuation for intra-individual variation. RESULTS: Regarding food groups in men, adjusted correlations ranged from 0.20 for vegetables and plasma vitamin C to 0.49 for fruits and plasma vitamin C, and from 0.40 for fish and plasma c20:5 n-3 (eicosapentaenoic acid [EPA]) to 0.55 for fish and plasma c22:6 n-3 (docosahexaenoic acid). In women, correlations ranged from 0.13 (nonsignificant) for vegetables and plasma vitamin C to 0.41 for fruits and vegetables and plasma beta carotene, and from 0.27 for fatty fish and EPA to 0.54 for fish and EPA+docosahexaenoic acid. Regarding micronutrients, adjusted correlations ranged from 0.36 (EPA) to 0.58 (vitamin C) in men and from 0.32 (vitamin C) to 0.38 (EPA) in women. CONCLUSIONS: The findings suggest that three nonconsecutive web-based dietary records provide reasonable estimates of true intake of fruits, vegetables, fish, beta carotene, vitamin C, and n-3 fatty acids. Along with other validation studies, this study shows acceptable validity of using such diet-assessment methods in large epidemiologic surveys and broadens new perspectives for epidemiology.


Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Frutas , Estado Nutricional , Alimentos Marinhos , Verduras , Vitaminas/administração & dosagem , Animais , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/sangue , Biomarcadores/sangue , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Registros de Dieta , Ingestão de Energia , Ácidos Graxos Ômega-3/sangue , Feminino , Peixes , França , Humanos , Internet , Masculino , Micronutrientes/administração & dosagem , Micronutrientes/sangue , Pessoa de Meia-Idade , Avaliação Nutricional , Estudos Prospectivos , Reprodutibilidade dos Testes , Vitaminas/sangue , beta Caroteno/administração & dosagem , beta Caroteno/sangue
20.
PLoS One ; 11(2): e0148118, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26862900

RESUMO

BACKGROUND: Whole rye (WR) consumption seems to be associated with beneficial health effects. Although rye fiber and polyphenols are thought to be bioactive, the mechanisms behind the health effects of WR have yet to be fully identified. This study in rats was designed to investigate whether WR can influence the metabolism of n-3 and n-6 long-chain fatty acids (LCFA) and gut microbiota composition. METHODS: For 12 weeks, rats were fed a diet containing either 50% WR or 50% refined rye (RR). The WR diet provided more fiber (+21%) and polyphenols (+29%) than the RR diet. Fat intake was the same in both diets and particularly involved similar amounts of essential (18-carbon) n-3 and n-6 LCFAs. RESULTS: The WR diet significantly increased the 24-hour urinary excretion of polyphenol metabolites-including enterolactone-compared with the RR diet. The WR rats had significantly more n-3 LCFA-in particular, eicosapentanoic (EPA) and docosahexanoic (DHA) acids-in their plasma and liver. Compared with the RR diet, the WR diet brought significant changes in gut microbiota composition, with increased diversity in the feces (Shannon and Simpson indices), decreased Firmicutes/Bacteroidetes ratio and decreased proportions of uncultured Clostridiales cluster IA and Clostridium cluster IV in the feces. In contrast, no difference was found between groups with regards to cecum microbiota. The WR rats had lower concentrations of total short-chain fatty acids (SCFA) in cecum and feces (p<0.05). Finally, acetate was lower (p<0.001) in the cecum of WR rats while butyrate was lower (p<0.05) in the feces of WR rats. INTERPRETATION: This study shows for the first time that WR consumption results in major biological modifications-increased plasma and liver n-3 EPA and DHA levels and improved gut microbiota profile, notably with increased diversity-known to provide health benefits. Unexpectedly, WR decreased SCFA levels in both cecum and feces. More studies are needed to understand the interactions between whole rye (fiber and polyphenols) and gut microbiota and also the mechanisms of action responsible for stimulating n-3 fatty acid metabolism.


Assuntos
Dieta , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Microbioma Gastrointestinal , Intestinos/microbiologia , Fígado/metabolismo , Secale , Animais , Peso Corporal , Ceco/metabolismo , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/metabolismo , Fezes , Comportamento Alimentar , Masculino , Espectrometria de Massas , Análise de Sequência com Séries de Oligonucleotídeos , Polifenóis/química , Ratos , Ratos Wistar
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