Publications by authors named "Fernandez-Larrea J"

An efficient liposomal system for screening the zinc ionophore activity of a selected library consisting of the most relevant dietary polyphenols is presented. The zinc ionophore activity was demonstrated by exploring the use of zinc-specific fluorophore FluoZin-3 loaded liposomes as simple membrane tools that mimic the cell membrane. The zinc ionophore activity was demonstrated as the capacity of polyphenols to transport zinc cations across the liposome membrane and increase the zinc-specific fluorescence of the encapsulated fluorophore FluoZin-3.

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Labile zinc, a tiny fraction of total intracellular zinc that is loosely bound to proteins and easily interchangeable, modulates the activity of numerous signaling and metabolic pathways. Dietary plant polyphenols such as the flavonoids quercetin (QCT) and epigallocatechin-gallate act as antioxidants and as signaling molecules. Remarkably, the activities of numerous enzymes that are targeted by polyphenols are dependent on zinc.

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The way specific procyanidins exert their anti-inflammatory effects is not fully understood. This study has investigated the capacity of different procyanidins to modulate lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production in THP1 human monocytes and their effects on the redox regulated protein kinases activity: IkB kinase beta (IKKb) and the extracellular signal-regulated kinase (ERK). LPS-triggered increase of ROS was prevented by cell pre-incubation with procyanidins.

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Chronic low-grade inflammation in obesity is characterized by macrophage accumulation in white adipose tissue (WAT) and abnormal cytokine production. We tested the hypothesis that grape-seed procyanidin extract (PE), with known anti-inflammatory and antioxidant effects, would improve local and systemic inflammation in diet-induced obesity rats. First, we analyzed the preventive effects of procyanidins (30 mg/kg per day) on rats fed a 60% kcal fat diet for 19 weeks.

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Catechins and their polymers procyanidins are health-promoting flavonoids found in edible vegetables and fruits. They act as antioxidants by scavenging reactive oxygen species and by chelating the redox-active metals iron and copper. They also behave as signaling molecules, modulating multiple cell signalling pathways and gene expression, including that of antioxidant enzymes.

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Flavonoids are beneficial compounds against risk factors for metabolic syndrome, but their effects and the mechanisms on glucose homeostasis modulation are not well defined. In the present study, we first checked the efficacy of grapeseed procyanidin extract (GSPE) for stimulating glucose uptake in insulin-resistant 3T3-L1 adipocytes. Results show that when resistance is induced with chronic insulin treatment, GSPE maintain a higher stimulating capacity than insulin.

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Objective: To determine whether proanthocyanidins can protect against dyslipidemia induced by a high-fat diet (HFD) and to address the mechanisms that underlie this hypolipidemic effect.

Design And Measurements: Female Wistar rats were fed on a HFD for 13 weeks. They were divided into two groups, one of which was treated with a grape seed proanthocyanidin extract (25 mg kg(-1) of body weight) for 10 days.

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Consumption of dietary flavonoids has been associated with reduced mortality and risk of cardiovascular disease, partially by reducing triglyceridemia. We have previously reported that a grape seed procyanidin extract (GSPE) reduces postprandial triglyceridemia in normolipidemic animals signaling through the orphan nuclear receptor small heterodimer partner (SHP) a target of the bile acid receptor farnesoid X receptor (FXR). Our aim was to elucidate whether FXR mediates the hypotriglyceridemic effect of procyanidins.

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Procyanidins are bioactive flavonoid compounds from fruits and vegetables that possess insulinomimetic properties, decreasing hyperglycaemia in streptozotocin-diabetic rats and stimulating glucose uptake in insulin-sensitive cell lines. Here we show that the oligomeric structures of a grape-seed procyanidin extract (GSPE) interact and induce the autophosphorylation of the insulin receptor in order to stimulate the uptake of glucose. However, their activation differs from insulin activation and results in differences in the downstream signaling.

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The potential beneficial effects of flavonoids on human health have aroused considerable interest and were initially attributed to their antioxidant activities. Recent studies have speculated that as well as their antioxidant role, flavonoids can act by modulating cell signaling pathways and/or gene expression. In this respect, we have used streptozotocin-induced diabetic rats as an oxidative stress model to study whether grape seed procyanidin extract (GSPE) regulates copper/zinc-superoxide dismutase (Cu/Zn-SOD), an enzyme that defends against oxidative stress.

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An off-line solid-phase extraction (SPE) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determining procyanidins, catechin, epicatechin, dimer, and trimer in plasma samples. In the validation procedure of the analytical method, linearity, precision, accuracy, detection limits (LODs), quantification limits (LOQs), and the matrix effect were studied. Recoveries of the procyanidins were higher than 84%, except for the trimer, which was 65%.

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Human and animal studies have demonstrated that procyanidin-rich diets reduce the risk of cardiovascular diseases and atherosclerosis. Some beneficial effects have been attributed to the well-known antioxidant activity of procyanidins. This study investigated another potential corrective role of procyanidins in cholesterol flux and inflammation in macrophage-derived foam cells.

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Procyanidins are the most abundant polyphenols in red wine and are also found in cereals, fruits, chocolate and tea. They exert many beneficial health effects, especially on the cardiovascular system (Bagchi et al. in Mutat Res 523-524:87-97, 2003; Williams et al.

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Hypertriglyceridemia is an independent risk factor in the development of cardiovascular diseases, and we have previously reported that oral administration of a grape seed procyanidin extract (GSPE) drastically decreases plasma levels of triglycerides (TG) and apolipoprotein B (ApoB) in normolipidemic rats, with a concomitant induction in the hepatic expression of the nuclear receptor small heterodimer partner (NR0B2/SHP). Our objective in this study was to elucidate whether SHP is the mediator of the reduction of TG-rich ApoB-containing lipoproteins triggered by GSPE. We show that GSPE inhibited TG and ApoB secretion in human hepatocarcinoma HepG2 cells and had and hypotriglyceridemic effect in wild-type mouse.

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Objective: The main objective of this study was to evaluate the effect of procyanidin intake on the level of inflammatory mediators in rats fed a hyperlipidic diet, which are a model of low-grade inflammation as they show an altered cytokine production.

Design: Male Zucker Fa/fa rats were randomly grouped to receive a low-fat (LF) diet, a high-fat (HF) diet or a high-fat diet supplemented with procyanidins from grape seed (HFPE) (3.45 mg/kg feed) for 19 weeks and were then euthanized.

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Procyanindin extract (PE) is a mixture of polyphenols, mainly procyanidins, obtained from grape seed with putative antiinflammatory activity. We evaluated the PE effect on RAW 264.7 macrophages stimulated with lipopolysaccharide plus interferon-gamma that show a rapid enhanced production of prostaglandin E2 (PGE2) and nitric oxide (NO).

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Procyanidins, a class of flavonoids, have clear and well-defined beneficial effects against several pathologies including cardiovascular heart disease. Now, studies in vivo are revealing the effects of procyanidins against obesity, where they prevent weight gain and adipose tissue mass increase, and against diabetes and insulin resistance, where they act as antihiperglycemic agents. Several mechanisms may be responsible for these effects.

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Procyanidins (PC) are of great interest in nutrition because they account for a major fraction of the total flavonoids ingested in Western diets and have health benefits in humans. However, it remains unknown which species of PC, namely, monomers, oligomers, or aromatic acid derivatives of gut microflora, are responsible for their beneficial effects in vivo. The high molecular complexity of PC extracts and PC-rich foods is a major problem in absorption studies.

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Red wine is a beverage that can exert a broad spectrum of health-promoting actions both in humans and laboratory animal models if consumed moderately. However, information about its effect on body weight is scarce. We have evaluated the effect of moderate red wine consumption on body weight and energy intake in male Zucker lean rats fed a hypercaloric diet for 8 weeks.

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Moderate consumption of red wine reduces risk of death from cardiovascular disease. The polyphenols in red wine are ultimately responsible for this effect, exerting antiatherogenic actions through their antioxidant capacities and modulating intracellular signaling pathways and transcriptional activities. Lipoprotein metabolism is crucial in atherogenesis, and liver is the principal organ controlling lipoprotein homeostasis.

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We characterized a novel protein of the Ras family, p19 (H-RasIDX). The c-H-ras proto-oncogene undergoes alternative splicing of the exon termed IDX. We show that the alternative p19 mRNA is stable and as abundant as p21 (p21 H-Ras4A) mRNA in all of the human tissues and cell lines tested.

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The DNA-binding protein Rap1p fulfills many different functions in the yeast cell. It targets 5% of the promoters, acting both as a transcriptional activator and as a repressor, depending on the DNA sequence context. In addition, Rap1p is an essential structural component of yeast telomeres, where it contributes to telomeric silencing.

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Single Rap1p DNA-binding sites are poor activators of transcription of yeast minimal promoters, even when fully occupied in vivo. This low efficiency is due to two independent repression mechanisms as follows: one that requires the presence of histones, and one that requires Hrs1p, a component of the RNA polymerase II mediator complex. Both repression mechanisms were greatly reduced for constructs with tandemly arranged sites.

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