Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin.

Apigenin (API) and luteolin (LUT) have been used as therapeutic agents in folk medicine for thousands of years. These compounds exert a variety of biological activities, including anticancer, antioxidant and antiinflammatory activities. This study investigated whether API and LUT could activate Nrf2-antioxidant response element (ARE)-mediated gene expression and induce antiinflammatory activities in human hepatoma HepG2 cells. The compounds did not exhibit any substantial toxicity at low doses (1.56-6.25 µm). The induction of ARE activity was assessed in HepG2-C8 cells after treatment with low doses of API and LUT for 6 and 12 h. It was found that the induction of ARE activity by these compounds at the higher doses was comparable to the effects of the positive control, SFN at a dose of 6.25 µm. Exposure to the PI3K inhibitor LY294002 abolished ARE activation by both API and LUT, whereas the ERK-1/2 inhibitor PD98059 only decreased ARE activity induced by API. Both compounds significantly increased the endogenous mRNA and protein levels of Nrf2 and Nrf2 target genes with important effects on heme oxygenase-1 (HO-1) expression. API and LUT significantly and dose-dependently decreased the production of nitric oxide (NO), nitric oxide synthase (iNOS) and cytosolic phospholipase A2 (cPLA2), which were induced by the treatment of HepG2 cells with 1 µg/ml of lipopolysaccharide (LPS) for 24 h. The results indicate that API and LUT significantly activate the PI3K/Nrf2/ARE system, and this activation may be responsible for their antiinflammatory effects, as demonstrated by the suppression of LPS-induced NO, iNOS and cPLA2.

Chilean native fruit extracts inhibit inflammation linked to the pathogenic interaction between adipocytes and macrophages.

Obesity is characterized by an increase in the infiltration of monocytes into the adipose tissue, causing an inflammatory condition associated with, for example, the development of insulin resistance. Thus, anti-inflammatory-based treatments could emerge as a novel and interesting approach. It has been reported that Chilean native fruits maqui (Aristotelia chilensis) and calafate (Berberis microphylla) present high contents of polyphenols, which are known for their antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the ability of extracts of these fruits to block the pathogenic interaction between adipocytes and macrophages in vitro and to compare its effect with blueberry (Vaccinium corymbosum) extract treatment, which has been already described to possess several biomedical benefits. RAW264.7 macrophages were treated with 5 µg/mL lipopolysaccharides (LPS), with conditioned media (CM) from fully differentiated 3T3-L1 adipocytes, or in a coculture (CC) with 3T3-L1 adipocytes, in the presence or absence of 100 µM [total polyphenolic content] of each extract for 24 h. The gene expression and secretion profile of several inflammatory markers were evaluated. Nitric oxide secretion induced by LPS, CM, and CC was reduced by the presence of maqui (-12.2%, -45.6%, and -14.7%, respectively) and calafate (-27.6%, -43.9%, and -11.8%, respectively) extracts. Gene expression of inducible nitric oxide synthase and TNF-α was inhibited and of IL-10 was induced by maqui and calafate extract incubation. In conclusion, the extracts of these fruits present important inhibitory-like features over the inflammatory response of the interaction between adipocytes and macrophages, comprising a potential therapeutic tool against comorbidities associated with obesity development.

Effects of functional olive oil enriched with its own phenolic compounds on endothelial function in hypertensive patients. A randomised controlled trial.

UNLABELLED: The additional health-promoting properties of functional virgin olive oil (FVOO) enriched with its own phenolic compounds (OOPC) versus the parental virgin olive oil (VOO) must be tested in appropriate human clinical trials. Our aim was to assess the effects of FVOO on endothelial function in hypertensive patients. Thirteen pre- and stage-1 hypertensive patients received a single dose of 30 mL of FVOO (OOPC=961 mg/kg) or VOO (OOPC=289 mg/kg) in a postprandial randomised, double blind, crossover trial. Endothelial function, measured as ischemic reactive hyperemia (IRH) and related biomarkers, were followed for 5h after consumption. Compared with VOO, FVOO increased IRH (P<0.05) and plasma Cmax of hydroxytyrosol sulphate, a metabolite of OOPC 2h postprandial (P=0.05). After FVOO ingestion, oxidised LDL decreased (P=0.010) in an inverse relationship with IRH AUC values (P=0.01). FVOO provided more benefits on endothelial function than a standard natural virgin olive oil in pre- and hypertensive patients. TRIAL REGISTRATION: isrctn.org. Identifier ISRCTN03450153.

Cancer chemoprevention by traditional chinese herbal medicine and dietary phytochemicals: targeting nrf2-mediated oxidative stress/anti-inflammatory responses, epigenetics, and cancer stem cells.

Excessive oxidative stress induced by reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive metabolites of carcinogens alters cellular homeostasis, leading to genetic/epigenetic changes, genomic instability, neoplastic transformation, and cancer initiation/progression. As a protective mechanism against oxidative stress, antioxidant/detoxifying enzymes reduce these reactive species and protect normal cells from endo-/exogenous oxidative damage. The transcription factor nuclear factor-erythroid 2 p45 (NF-E2)-related factor 2 (Nrf2), a master regulator of the antioxidative stress response, plays a critical role in the expression of many cytoprotective enzymes, including NAD(P)H: quinine oxidoreductase (NQO1), heme oxygenase-1 (HO-1), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST). Recent studies demonstrated that many dietary phytochemicals derived from various vegetables, fruits, spices, and herbal medicines induce Nrf2-mediated antioxidant/detoxifying enzymes, restore aberrant epigenetic alterations, and eliminate cancer stem cells (CSCs). The Nrf2-mediated antioxidant response prevents many age-related diseases, including cancer. Owing to their fundamental contribution to carcinogenesis, epigenetic modifications and CSCs are novel targets of dietary phytochemicals and traditional Chinese herbal medicine (TCHM). In this review, we summarize cancer chemoprevention by dietary phytochemicals, including TCHM, which have great potential as a safer and more effective strategy for preventing cancer.

Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression.

Reactive metabolites from carcinogens and oxidative stress can drive genetic mutations, genomic instability, neoplastic transformation, and ultimately carcinogenesis. Numerous dietary phytochemicals in vegetables/fruits have been shown to possess cancer chemopreventive effects in both preclinical animal models and human epidemiological studies. These phytochemicals could prevent the initiation of carcinogenesis via either direct scavenging of reactive oxygen species/reactive nitrogen species (ROS/RNS) or, more importantly, the induction of cellular defense detoxifying/antioxidant enzymes. These defense enzymes mediated by Nrf2-antioxidative stress and anti-inflammatory signaling pathways can contribute to cellular protection against ROS/RNS and reactive metabolites of carcinogens. In addition, these compounds would kill initiated/transformed cancer cells in vitro and in in vivo xenografts via diverse anti-cancer mechanisms. These mechanisms include the activation of signaling kinases (e.g., JNK), caspases and the mitochondria damage/cytochrome c pathways. Phytochemicals may also have anti-cancer effects by inhibiting the IKK/NF-κB pathway, inhibiting STAT3, and causing cell cycle arrest. In addition, other mechanisms may include epigenetic alterations (e.g., inhibition of HDACs, miRNAs, and the modification of the CpG methylation of cancer-related genes). In this review, we will discuss: the current advances in the study of Nrf2 signaling; Nrf2-deficient tumor mouse models; the epigenetic control of Nrf2 in tumorigenesis and chemoprevention; Nrf2-mediated cancer chemoprevention by naturally occurring dietary phytochemicals; and the mutation or hyper-expression of the Nrf2-Keap1 signaling pathway in advanced tumor cells. The future development of dietary phytochemicals for chemoprevention must integrate in vitro signaling mechanisms, relevant biomarkers of human diseases, and combinations of different phytochemicals and/or non-toxic therapeutic drugs, including NSAIDs.

A perspective on dietary phytochemicals and cancer chemoprevention: oxidative stress, nrf2, and epigenomics.

Oxidative stress is caused by an imbalance of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and the antioxidative stress defense systems in cells. ROS/RNS or carcinogen metabolites can attack intracellular proteins, lipids, and nucleic acids, which can result in genetic mutations, carcinogenesis, and other diseases. Nrf2 plays a critical role in the regulation of many antioxidative stress/antioxidant and detoxification enzyme genes, such as glutathione S-transferases (GSTs), NAD(P)H:quinone oxidoreductase 1 (NQO1), UDP-glucuronyl transferases (UGTs), and heme oxygenase-1 (HO-1), directly via the antioxidant response element (ARE). Recently, many studies have shown that dietary phytochemicals possess cancer chemopreventive potential through the induction of Nrf2-mediated antioxidant/detoxification enzymes and anti-inflammatory signaling pathways to protect organisms against cellular damage caused by oxidative stress. In addition, carcinogenesis can be caused by epigenetic alterations such as DNA methylation and histone modifications in tumor-suppressor genes and oncogenes. Interestingly, recent studies have shown that several naturally occurring dietary phytochemicals can epigenetically modify the chromatin, including reactivating Nrf2 via demethylation of CpG islands and the inhibition of histone deacetylases (HDACs) and/or histone acetyltransferases (HATs). The advancement and development of dietary phytochemicals in cancer chemoprevention research requires the integration of the known, and as-yet-unknown, compounds with the Nrf2-mediated antioxidant, detoxification, and anti-inflammatory systems and their in vitro and in vivo epigenetic mechanisms; human clinical efficacy studies must also be performed.

Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability.

Cancer remains to be one of the leading causes of death in the United States and around the world. The advent of modern drug-targeted therapies has undeniably improved cancer patients' cares. However, advanced metastasized cancer remains untreatable. Hence, continued searching for a safer and more effective chemoprevention and treatment is clearly needed for the improvement of the efficiency and to lower the treatment cost for cancer care. Cancer chemoprevention with natural phytochemical compounds is an emerging strategy to prevent, impede, delay, or cure cancer. This review summarizes the latest research in cancer chemoprevention and treatment using the bioactive components from natural plants. Relevant molecular mechanisms involved in the pharmacological effects of these phytochemicals are discussed. Pharmaceutical developmental challenges and opportunities in bringing the phytochemicals into the market are also explored. The authors wish to expand this research area not only for their scientific soundness, but also for their potential druggability.

Mediterranean diet supplemented with coenzyme Q10 induces postprandial changes in p53 in response to oxidative DNA damage in elderly subjects.

Coenzyme Q10 (CoQ) is a powerful antioxidant that reduces oxidative stress. We explored whether the quality of dietary fat alters postprandial oxidative DNA damage and whether supplementation with CoQ improves antioxidant capacity by modifying the activation/stabilization of p53 in elderly subjects. In this crossover study, 20 subjects were randomly assigned to receive three isocaloric diets during 4 weeks each: (1) Mediterranean diet (Med diet), (2) Mediterranean diet supplemented with CoQ (Med+CoQ diet), and (3) saturated fatty acid-rich diet (SFA diet). Levels of mRNAs were determined for p53, p21, p53R2, and mdm2. Protein levels of p53, phosphorylated p53 (Ser20), and monoubiquitinated p53 were also measured, both in cytoplasm and nucleus. The extent of DNA damage was measured as plasma 8-OHdG. SFA diet displayed higher postprandial 8-OHdG concentrations, p53 mRNA and monoubiquitinated p53, and lower postprandial Mdm2 mRNA levels compared with Med and Med+CoQ diets (p < 0.05). Moreover, Med+CoQ diet induced a postprandial decrease of cytoplasmatic p53, nuclear p-p53 (Ser20), and nuclear and cytoplasmatic monoubiquitinated p53 protein (p < 0.05). In conclusion, Med+CoQ diet improves oxidative DNA damage in elderly subjects and reduces processes of cellular oxidation. Our results suggest a starting point for the prevention of oxidative processes associated with aging.

Postprandial antioxidant effect of the Mediterranean diet supplemented with coenzyme Q10 in elderly men and women.

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial cellular oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) lowers postprandial oxidative stress in an elderly population. In this randomized crossover study, 20 participants were assigned to receive three isocaloric diets for periods of 4 week each: (1) Mediterranean diet supplemented with CoQ (Med+CoQ diet), (2) Mediterranean diet (Med diet), and (3) saturated fatty acid-rich diet (SFA diet). After a 12-h fast, the volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. CoQ, lipid peroxides (LPO), oxidized low-density lipoprotein (oxLDL), protein carbonyl (PC), total nitrite, nitrotyrosine plasma levels, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and ischemic reactive hyperaemia (IRH) were determined. Med diet produced a lower postprandial GPx activity and a lower decrease in total nitrite level compared to the SFA diet. Med and Med+CoQ diets induced a higher postprandial increase in IRH and a lower postprandial LPO, oxLDL, and nitrotyrosine plasma levels than the SFA diet. Moreover, the Med+CoQ diet produced a lower postprandial decrease in total nitrite and a greater decrease in PC levels compared to the other two diets and lower SOD, CAT, and GPx activities than the SFA diet.In conclusion, Med diet reduces postprandial oxidative stress by reducing processes of cellular oxidation and increases the action of the antioxidant system in elderly persons and the administration of CoQ further improves this redox balance.

Chronic dietary fat intake modifies the postprandial response of hemostatic markers to a single fatty test meal.

BACKGROUND: Hemostasis is the result of a complex equilibrium between coagulation and fibrinolysis, and the influence of different dietary models on this equilibrium is not entirely known. OBJECTIVE: The objective was to compare the effects of the chronic intake of different dietary models on postprandial hemostasis. DESIGN: In a randomized crossover design, 20 healthy men consumed for 28 d each diets rich in monounsaturated fatty acids (MUFAs), saturated fatty acids (SFAs), and carbohydrates plus n-3 fatty acids (CHO/N3). Fasting and postprandial hemostatic factors (factor VII coagulant activity, plasminogen activator inhibitor-1, tissue-type plasminogen activator, d-dimer, and thromboxane B(2)) were measured; meal tests for the postprandial measures were based on butter, virgin olive oil, and walnuts for the SFA, MUFA, and CHO/N3 diets, respectively. RESULTS: There were no differences in the fasting variables after the dietary periods. After the 3 fatty meals were consumed, we observed an increase in thromboxane B(2) and d-dimer and a reduction in tissue plasminogen activator, irrespective of the dietary model. The MUFA or CHO/N3 meals lowered postprandial concentrations of factor VII coagulant activity, although the reduction was greater after the MUFA-enriched meal. The concentration of plasminogen activator inhibitor-1 was greater after the SFA meal than after the other 2 meals. CONCLUSIONS: The administration of a fatty meal induces a postprandial procoagulant tendency, irrespective of the type of fat consumed. However, the use of a dietary model rich in SFA creates a more procoagulant environment than does a model that includes MUFA or CHO/N3 as the source of fatty acids.

Olive oil and the haemostatic system.

Interest in the Mediterranean diet (MD) has grown worldwide due to its link with greater longevity and lower cardiovascular disease rate, cancer and age cognitive decline. Despite the high complexity of its nutrients composition, olive oil emerges as its principal food, since it provides the higher percent of energy and a lot of bioactive compounds. In this review we will discuss the benefits of diets enriched in virgin olive oil, whose effects are probably due not only to its oleic acid content but also to its other potentially health-promoting components. Traditionally, the benefits of MD were linked to its effect on lipoprotein metabolism but today we realise that there exists a whole sheaf of other benefits, including the components of haemostasis: platelet function, thrombogenesis and fibrinolysis. A diet enriched in virgin olive oil can reduce the sensitivity of platelets to aggregation, decreasing von Willebrand and tromboxane B2 plasma levels. Moreover a particular interest has arisen about its capacity to decrease fasting Factor VII plasma levels and to avoid or modulate its postprandial activation. Also Tissue Factor expression in mononuclear cells could be reduced with the chronic intake of virgin olive oil and finally, studies performed in different experimental situation have shown that it could also increase fibrinolytic activity, reducing plasma concentration of Plasma Activator Inhibitor type-1.

Intake of phenol-rich virgin olive oil improves the postprandial prothrombotic profile in hypercholesterolemic patients.

BACKGROUND: Oxidative stress associated with postprandial lipemia contributes to endothelial dysfunction, which shifts hemostasis to a more thrombogenic state. OBJECTIVE: We investigated whether a high concentration of phenols in olive oil can partly reverse this phenomenon. DESIGN: Twenty-one hypercholesterolemic volunteers received 2 breakfasts rich in olive oils with different phenolic contents (80 or 400 ppm) according to a randomized, sequential crossover design. Plasma concentrations of lipid fractions, factor VII antigen (FVIIag), activated factor VII (FVIIa), and plasminogen activator inhibitor-1 (PAI-1) activity were measured at baseline and postprandially. RESULTS: Concentrations of FVIIa increased less (P = 0.018) and plasma PAI-1 activity decreased more (P = 0.021) 2 h after the high-phenol meal than after the low-phenol meal. FVIIa concentrations 120 min after intake of the olive oil with a high phenol content correlated positively with fasting plasma triacylglycerols (P = 0.001), area under the curve (AUC) of triacylglycerols (P = 0.001), and AUC of nonesterified fatty acids (P = 0.024) and negatively with hydroxytyrosol plasma concentrations at 60 min (P = 0.039) and fasting HDL-cholesterol concentrations (P = 0.005). PAI-1 positively correlated with homeostasis model assessment of insulin resistance (P = 0.005) and fasting triacylglycerols (P = 0.025) and inversely with adiponectin (P = 0.026). In a multivariate analysis, the AUCs of nonesterified fatty acids (R(2) = 0.467; beta: 0.787; SE: 0.02; P < 0.001) and adiponectin (R(2) = 0.232; beta: -1.594; SE: 0.629; P < 0.05) were the strongest predictors of plasma FVIIa and PAI-1, respectively. CONCLUSIONS: A virgin olive oil with a high content of phenolic compounds changes the postprandial hemostatic profile to a less thrombogenic state.

Low-magnesium uranium-calcite with high degree of crystallinity and gigantic luminescence emission.

Cabrera (Madrid) low-Mg calcites exhibit: (i) an unusual twofold elevation in X-ray diffraction pattern intensity; (ii) a 60-fold elevation of luminescence emission, compared to six common natural calcites selected for comparison purposes; (iii) a natural relatively high radiation level of circa 200 nSvh(-1) not detected in 1300 other calcites from the Natural History Museum of Madrid. Calcites were analysed by the X-ray diffraction powder method (XRD), cathodo-luminescence spectroscopy in scanning electron microscopy (CL-SEM), thermoluminescence (TL), differential thermal analysis (DTA), X-ray fluorescence spectrometry (XRF) and particle size distribution (PSD). The Cabrera calcite study shows: (i) helicoidally distributed steps along the (0001) orientation; (ii) protuberance defects onto the (0001) surface, observed by SEM; (iii) XRF chemical contents of 0.03% MgO, 0.013% of Y(2)O(3), and 0.022% of U(3)O(8), with accessory amounts of rare earth elements (REE); (iv) DTA dissociation temperature of 879 degrees C; (v) TL maxima peaks at 233 and 297 degrees C whose areas are 60 times compared to other calcites; (vi) spectra CL-SEM bands at 2.0 and 3.4 eV in the classic structure of Mn(2+) activators; (vii) a twofold XRD pattern explained given that sample is a low-Mg calcite. The huge TL and CL emissions of the Cabrera calcite sample must be linked with the uranyl group presence. This intense XRD pattern in low-Mg calcites could bring into being analytical errors.

Olive oil and haemostasis: a review on its healthy effects.

UNLABELLED: Interest in the Mediterranean diet (MD) has grown worldwide. Despite the high complexity of its nutrients composition, olive oil emerges as its principal food, since it provides the higher percentage of energy and a lot of bioactive compounds. OBJECTIVE: In this review, we will discuss the benefits of diets enriched in virgin olive oil, whose effects are probably due not only to its oleic acid content but also to its other potentially health-promoting components. METHODS: Traditionally, the benefits of MD were linked to its effect on lipoprotein metabolism, but today we realise that there exists a whole sheaf of other benefits, including the components of haemostasis: platelet function, thrombogenesis and fibrinolysis. RESULTS: A diet enriched in virgin olive oil can reduce the sensitivity of platelets to aggregation, decreasing von Willebrand and thromboxane B2 plasma levels. Moreover, a particular interest has aroused about its capacity to decrease fasting factor VII plasma levels and to avoid or modulate its postprandial activation. In addition, tissue factor expression in mononuclear cells could be reduced with the chronic intake of virgin olive oil, and finally, studies performed in different experimental situation have shown that it could also increase fibrinolytic activity, reducing plasma concentration of plasma activator inhibitor type-1 (PAI-1). CONCLUSION: The MD is an alimentary model with a high content of monounsaturated fats that is capable of inducing a wide range of biological effects on the cardiovascular system. The application of modern focuses of study will dilucidate in the future the biological and clinical interest of these findings.

Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients.

OBJECTIVES: The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity. BACKGROUND: Endothelial-dependent vasodilatation is impaired during the postprandial state, and oxidative stress could play a key role in its development. METHODS: Twenty-one hypercholesterolemic volunteers received two breakfasts, using a randomized sequential crossover design. Both arms received the same olive oil, but one had its phenolic acid content reduced from 400 to 80 ppm. Ischemic reactive hyperemia (IRH) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake. Postprandial plasma concentrations of lipid fractions, lipoperoxides (LPO), 8-epi prostaglandin-F(2alpha), and nitrates/nitrites (NO(x)) were obtained at baseline and after 2 h of the fat meal. RESULTS: The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function, as well as a greater increase in concentrations of NO(x) (p < 0.001) and a lower increase in LPO (p < 0.005) and 8-epi prostaglandin-F2alpha (p < 0.001) than the ones induced by the low polyphenol fat meal. A positive correlation was found to exist between NO(x) and enhanced endothelial function at the second hour (r = 0.669; p < 0.01). Furthermore, a negative correlation was found between IRH and LPO (r = -0.203; p < 0.05) and 8-epi prostaglandin-F2alpha levels (r = -0.440; p < 0.05). CONCLUSIONS: A meal containing high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postprandial state. This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites.

A polymorphism exon 1 variant at the locus of the scavenger receptor class B type I (SCARB1) gene is associated with differences in insulin sensitivity in healthy people during the consumption of an olive oil-rich diet.

UNLABELLED: Scavenger receptor class B type I (SCARB1) was described as the first high-density lipoprotein receptor. Increasing evidence indicates that SCARB1 plays additional roles particularly in type 2 diabetes mellitus. Our aim was to determine whether the presence of an exon 1 (G-->A) polymorphism at the SCARB1 gene modifies the insulin sensitivity to dietary fat. METHODS: We studied 59 healthy volunteers (30 men and 29 women, 42 G/G homozygous and 17 G/A heterozygous). Subjects consumed three diets for 4 wk each: a saturated fatty acid (SFA)-rich diet (38% fat, 20% SFA), followed by a carbohydrate (CHO)-rich diet (30% fat, 55% CHO) or a monounsaturated fatty acid (MUFA)-rich diet (38% fat, 22% MUFA) after a randomized crossover design. For each diet, we investigated peripheral insulin sensitivity with the insulin suppression test. RESULTS: Steady-state plasma glucose after the MUFA diet was lower in G/A compared with G/G subjects (P = 0.030). This effect was not observed after CHO and SFA diets (P = 0.177 and 0.957, respectively). Plasma nonesterified free fatty acid values were lower in subjects carrying the A allele for all the diet periods. CONCLUSIONS: Our findings show that carriers of the G/A genotype have significant increases in insulin sensitivity after a MUFA-rich diet compared with G/G individuals.

Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor kappaB in peripheral blood mononuclear cells from healthy men.

BACKGROUND: Nuclear transcription factor kappaB (NF-kappaB) plays an important role in atherosclerosis by modulating gene expression. Postprandial lipemia has been correlated with an increase in NF-kappaB activation in vascular cells and it is associated with an increase in postprandial triacylglycerol-rich lipoproteins, which are involved in the development of atherosclerotic plaque. OBJECTIVE: The objective of this study was to determine the effect of the intakes of 3 different foods with different fat compositions on the postprandial activation of monocyte NF-kappaB. DESIGN: Eight healthy men followed a 4-wk baseline diet and then consumed 3 fat-load meals consisting of 1 g fat/kg body wt (65% fat) according to a randomized crossover design. Each meal had a different fatty acid composition, and the consumption of each meal was separated by 1 wk. The compositions of the 3 test meals were as follows: olive oil meal [22% saturated fatty acids (SFAs), 38% monounsaturated fatty acids (MUFAs), 4% polyunsaturated fatty acids (PUFAs), and 0.7% alpha-linolenic acid], butter meal (38% SFAs, 22% MUFAs, 4% PUFAs, and 0.7% alpha-linolenic acid), and walnut meal (20% SFAs, 24% MUFAs, 16% PUFAs, and 4% alpha-linolenic acid). RESULTS: Ingestion of the olive oil meal did not elicit NF-kappaB activation compared with ingestion of either the butter meal at 3 h (P <0.05) or the walnut meal at 9 h (P <0.05). There was no significant difference in the postprandial triacylglycerol response between the 3 meals. CONCLUSIONS: Consumption of an olive oil-enriched meal does not activate NF-kappaB in monocytes as do butter and walnut-enriched meals. This effect could enhance the cardioprotective effect of olive oil-enriched diets.

Polymorphism exon 1 variant at the locus of the scavenger receptor class B type I gene: influence on plasma LDL cholesterol in healthy subjects during the consumption of diets with different fat contents.

BACKGROUND: The association between polymorphisms in the scavenger receptor class B type I (SRB-I) gene and variations in basal plasma concentrations of cholesterol in humans has recently been described. OBJECTIVE: The objective of the study was to determine whether the exon 1 variant (G-->A) at the SRB-I gene is associated with the lipid response to the content and quality of dietary fat in healthy subjects. DESIGN: We studied 97 healthy volunteers with exon 1 polymorphism [65 homozygous for allele 1 (1/1) and 32 heterozygous for allele 2 (1/2)]. Both groups consumed 3 diets lasting 4 wk each. The first was a saturated fatty acid (SFA)-rich diet (38% fat, 20% SFA), which was followed by a carbohydrate (Cho)-rich diet (30% fat, < 10% SFA, 55% carbohydrate) or a monounsaturated fatty acid (MUFA), olive oil-rich diet (38% fat, 22% MUFA) according to a randomized crossover design. At the end of each dietary period, plasma concentrations of triacylglycerol and of total, LDL, and HDL cholesterol were measured. RESULTS: Carriers of the 1/2 genotype had a trend toward higher concentrations of LDL cholesterol (P < 0.11) after the SFA-rich diet than did those who were homozygous for 1/1. Carriers of the mutation showed a significantly greater (P = 0.007) decrease in LDL-cholesterol concentrations (-23%) in changing from an SFA-rich diet to a Cho-rich diet than did noncarriers of the mutation (-16%). CONCLUSION: Carriers of the minority allele, 1/2, are more susceptible to the presence of SFA in the diet because of a greater increase in LDL cholesterol.

La dieta mediterránea mejora la resistencia a la oxidación de las lipoproteínas de baja densidad / Mediterranean diet improves low density lipoprotein susceptibility to oxidative modifications

Fundamento: Numerosos paneles de expertos, en especial de países anglosajones, recomiendan la dieta pobre en grasa para la prevención de enfermedades cardiovasculares. Sin embargo, la tasa de muerte por cardiopatía isquémica es baja en los países del área mediterránea, lo que puede ser debido al alto porcentaje de grasa monoinsaturada proporcionada por el aceite de oliva en la dieta. Por ello hemos comparado el efecto de ambas dietas sobre la susceptibilidad in vitro a la oxidación de las lipoproteínas de baja densidad (LDL), pieza clave en el inicio y desarrollo de la arteriosclerosis. Sujetos y métodos: Cuarenta y un sujetos varones sanos normolipémicos fueron sometidos a tres períodos de dieta, de 4 semanas de duración cada uno, consistentes en una dieta rica en grasa saturada (SAT: 38 por ciento grasa, 20 por ciento saturada), otra pobre en grasa (NCEP-I: 28 por ciento grasa, 10 por ciento saturada) y una dieta medi-terránea (38 por ciento grasa, 22 por ciento de grasa monoinsaturada). Al final de cada período dietético se determinaron las concentraciones plasmáticas de colesterol total, cLDL, cHDL, triglicéridos, apoproteínas A-I y B, *-tocoferol y la susceptibilidad a la oxidación de las LDL in vitro. Resultados: Ambas dietas hipolipemiantes produjeron un descenso significativo de las concentraciones plasmáticas de colesterol total, cLDL y apo B, mientras que sólo la dieta NCEP-I disminuyó el cHDL. La sustitución de una dieta rica en grasa saturada o de una dieta rica en hidratos de carbono por una dieta mediterránea aumentó la resistencia a la oxidación de las LDL al prolongarse el tiempo de latencia (p < 0,038) e inducir un descenso (p < 0,001) en la tasa de progresión de la curva de cinética de oxidación de las LDL. Conclusión: Nuestros resultados indican que el consumo de una dieta mediterránea rica en aceite de oliva, además de mejorar el índice aterogénico (colesterol total/cHDL), aumenta la resistencia a la oxidación de las LDL en comparación con la dieta pobre en grasa. Ello nos hace aconsejar el modelo de dieta mediterránea para la prevención de las enfermedades cardiovasculares. (AU)