dinoprost and Dyslipidemias

To evaluate the effects of a hypoenergetic diet (HD)associated with açaí pulp consumption on oxidative stress, antioxidant status and inflammatory biomarkers in overweight, dyslipidemic individuals.. A randomized, double-blind, placebo-controlled clinical trial was conducted for 90 days. The study began with a 30-day run-in period, during which the intervention was exclusively a HD. Following this period, volunteers were randomized into 2 groups, and 200 g of either açaí pulp or placebo were added to the HD for 60 days. Anthropometric measurements, arterial pressure, oxidative stress and antioxidant status biomarkers, inflammatory and biochemical biomarkers were evaluated.. Sixty-nine volunteers completed the clinical trial, 30 of which were in the HD + açaí group and 39 in HD + placebo group. Plasma 8-isoprostane concentrations significantly reduced 60 days after the intervention in the açaí group (p = 0.000), and there was a significant difference between the groups (açaí versus placebo; p = 0.037). Regarding inflammatory status parameters, a significant reduction in IL-6 was observed in the HD + açaí group (p = 0.042), and IFN-γ decreased significantly in both groups, HD + açaí (p = 0.001) and HD + placebo (p = 0.008); there were, however, no differences between the groups. Lipid profile parameters and blood glucose levels did not show change, regardless of nutritional intervention.. The addition of açaí to a HD, for 60 days, reduced oxidative stress and improved inflammation in overweight, dyslipidemic individuals.

Topics: Adult; Antioxidants; Biomarkers; Diet, Reducing; Dinoprost; Double-Blind Method; Dyslipidemias; Energy Intake; Euterpe; Female; Gene Expression Regulation; Humans; Inflammation; Interferon-gamma; Interleukin-6; Male; Middle Aged; Overweight; Oxidative Stress

Oxidative stress plays an essential role in the pathogenesis of type 2 diabetes. Anthocyanin, a natural antioxidant, has been reported to reduce oxidative stress and to attenuate insulin resistance and diabetes in animal models; however, the translation of these observations to humans has not been fully tested.. This study was designed to investigate the effects of purified anthocyanins on dyslipidemia, oxidative status, and insulin sensitivity in patients with type 2 diabetes.. A total of 58 diabetic patients were given 160 mg of anthocyanins twice daily or placebo (n = 29/group) for 24 wk in a randomized, placebo-controlled, double-blind trial. Participants and investigators were masked to treatment allocation.. Anthocyanin supplementation significantly decreased serum LDL cholesterol (by 7.9%; P < 0.05), triglycerides (by 23.0%; P < 0.01), apolipoprotein (apo) B-48 (by 16.5%; P < 0.05), and apo C-III (by 11.0%; P < 0.01) and increased HDL cholesterol (by 19.4%; P < 0.05) compared with placebo after the 24-wk intervention. In addition, patients in the anthocyanin group showed higher total radical-trapping antioxidant parameter and ferric ion reducing antioxidant power values than did patients in the placebo group (both P < 0.05). Serum concentrations of 8-iso-prostaglandin F2α, 13-hydroxyoctadecadienoic acid, and carbonylated proteins in patients in the anthocyanin group were significantly less than in patients in the placebo group (23.4%, 25.8%; P < 0.01 and 20%; P = 0.022, respectively). Furthermore, supplementation with anthocyanin lowered fasting plasma glucose (by 8.5%; P < 0.05) and homeostasis model assessment for insulin resistance index (by 13%; P < 0.05), and elevated serum adiponectin (by 23.4%; P < 0.01) and β-hydroxybutyrate (by 42.4%; P = 0.01) concentrations compared with placebo supplementation.. These findings demonstrate that anthocyanin supplementation exerts beneficial metabolic effects in subjects with type 2 diabetes by improving dyslipidemia, enhancing antioxidant capacity, and preventing insulin resistance. This trial was registered at www.clinicaltrials.gov as NCT02317211.

Topics: 3-Hydroxybutyric Acid; Aged; Anthocyanins; Antioxidants; Apolipoprotein B-48; Apolipoprotein C-III; Blood Glucose; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dietary Supplements; Dinoprost; Dose-Response Relationship, Drug; Double-Blind Method; Dyslipidemias; Female; Humans; Insulin; Insulin Resistance; Linoleic Acids; Male; Middle Aged; Nutrition Assessment; Oxidative Stress; Triglycerides

The postprandial triglyceride-rich lipoprotein (TRL) concentration is a recognized independent cardiovascular disease risk factor. Diet is the natural approach for these postprandial alterations. Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3s) are associated with a lower cardiovascular disease risk.. This randomized controlled study evaluated, in persons with a high risk of cardiovascular disease, the effects of diets naturally rich in polyphenols and/or marine LCn3s on plasma TRLs and urinary 8-isoprostane concentrations, a biomarker of oxidative stress.. According to a 2 × 2 factorial design, 86 overweight/obese individuals with a large waist circumference and any other component of the metabolic syndrome were randomly assigned to an isoenergetic diet 1) poor in LCn3s and polyphenols, 2) rich in LCn3s, 3) rich in polyphenols, or 4) rich in LCn3s and polyphenols. The diets were similar in all other components. Before and after the 8-wk intervention, fasting and postmeal TRLs and 8-isoprostane concentrations in 24-h urine samples were measured.. Dietary adherence was good in all participants. Polyphenols significantly reduced fasting triglyceride concentrations (2-factor ANOVA) in plasma (P = 0.023) and large very-low-density lipoproteins (VLDLs) (P = 0.016) and postprandial triglyceride total area under the curve in plasma (P = 0.041) and large VLDLs (P = 0.004). LCn3s reduced postprandial chylomicron cholesterol and VLDL apolipoprotein B-48. The concentrations of urinary 8-isoprostane decreased significantly with the polyphenol-rich diets. Lipoprotein changes induced by the intervention significantly correlated with changes in 8-isoprostane.. Diets naturally rich in polyphenols positively influence fasting and postprandial TRLs and reduce oxidative stress. Marine LCn3s reduce TRLs of exogenous origin. Through their effects on postprandial lipemia and oxidative stress, polyphenols may favorably affect cardiovascular disease risk.

Topics: Adult; Aged; Antioxidants; Biomarkers; Body Mass Index; Diet; Dinoprost; Dyslipidemias; Fasting; Fatty Acids, Omega-3; Female; Humans; Lipoproteins; Male; Metabolic Syndrome; Middle Aged; Overweight; Oxidative Stress; Polyphenols; Postprandial Period; Triglycerides

Oxidative stress plays an important role in atherosclerosis. Both F2-isoprostane (8-iso-PGF2a) and oxidized low-density lipoprotein (ox-LDL) have emerged as biomarkers of oxidative stress and have been proposed as useful biomarkers that could potentially be used as indicators of cardiovascular disease.. This is a prespecified analysis of a prospective, randomized, open-label, blinded endpoint (PROBE) study (ClinicalTrials.gov identifier: NCT01010516). Patients (N = 100) with mixed dyslipidemia on a standard statin dose (10-40 mg simvastatin or 10-20 mg atorvastatin or 5-10 mg rosuvastatin) who had not achieved lipid targets were randomized to switch to the highest dose of rosuvastatin (40 mg/day) or to add-on-statin extended release nicotinic acid (ER-NA)/laropiprant (LRPT) (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks) or to add-on-statin micronized fenofibrate (200 mg/day) for a total of 3 months. Levels of plasma and urine F2-isoprostane and plasma ox-LDL were assessed at baseline and 3 months later.. Plasma F2-isoprostane levels decreased similarly in all groups. On the other hand, both ox-LDL and urine F2-isoprostane levels decreased similarly in the add-on ER-NA/LRPT and rosuvastatin monotherapy group, while a less pronounced decrease was observed in the add-on fenofibrate group.. All treatment interventions reduced the concentration of the assessed oxidative stress markers, but the reduction was more pronounced in the add-on ER-NA/LRPT and rosuvastatin monotherapy groups, compared with add-on fenofibrate. Specifically designed studies should address the abovementioned risk factors modulation in terms of cardiovascular risk.

Topics: Aged; Apolipoprotein B-100; Atorvastatin; Bilirubin; Biomarkers; Dinoprost; Drug Therapy, Combination; Dyslipidemias; Female; Fenofibrate; Fluorobenzenes; Greece; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Indoles; Lipoproteins, LDL; Male; Middle Aged; Niacin; Oxidative Stress; Prospective Studies; Pyrimidines; Pyrroles; Rosuvastatin Calcium; Simvastatin; Sulfonamides; Time Factors; Treatment Outcome; Uric Acid

Mixed dyslipidemia, oxidative stress and inflammation are related to a high risk for cardiovascular events. The aim of this open-label randomized study was to compare the effects of high-dose rosuvastatin, low-dose rosuvastatin plus fenofibrate and low-dose rosuvastatin plus omega 3 fatty acids on inflammation and oxidative stress indices in patients with mixed dyslipidemia.. Ninety patients with mixed dyslipidemia participated in the study. Patients were randomly allocated to receive rosuvastatin 40 mg (n = 30, group R), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 30, group RF) or rosuvastatin 10 mg plus omega 3 fatty acids 2 g daily (n = 30, group RΩ). Plasma and high-density lipoprotein (HDL)-associated lipoprotein-associated phospholipase A2 (LpPLA2) activities, high-sensitivity C reactive protein (hsCRP), plasma isoprostane and paraoxonase (PON1) activities were measured at baseline and after 3 months of treatment.. Serum concentrations of non-HDL cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly reduced in all study groups. However, these changes were more pronounced in the rosuvastatin monotherapy group. In all treatment groups a significant reduction in total plasma LpPLA2 activity was observed (by 41, 38 and 30% for groups R, RF and RΩ, respectively). This decrease was greater in the R and RF groups compared with the RΩ combination (p < 0.05). HDL-LpPLA2 activity was increased more in the RF group (+43%) compared with the R and RΩ groups (+ 18% and + 35%, respectively; p < 0.05 for both comparisons). In all treatment groups there was a nonsignificant reduction in plasma 8-iso-PGF2α levels. A 53% reduction of hsCRP levels was observed in the R group, while in the RF and RΩ groups the reduction was 28 and 23%, respectively (p < 0.05 and p < 0.01 for the comparisons of group R with groups RF and RΩ, respectively). No significant changes were observed in PON activities in all treatment groups.. The greater non-HDL-C- and LDL-C-lowering efficiency of rosuvastatin monotherapy along with its more potent effect on LpPLA2 activity and hsCRP levels indicate that this regimen is a better treatment option for patients with mixed dyslipidemia.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adult; Aged; Aryldialkylphosphatase; C-Reactive Protein; Dinoprost; Drug Combinations; Dyslipidemias; Fatty Acids, Omega-3; Female; Fenofibrate; Fluorobenzenes; Humans; Hypolipidemic Agents; Inflammation; Lipids; Male; Middle Aged; Oxidative Stress; Pyrimidines; Rosuvastatin Calcium; Sulfonamides

Recent years have seen increased numbers of children with conditions that contribute strongly to atherosclerotic disease, such as passive smoking, obesity, and dyslipidemia. In the present study, we evaluated the utility of non-invasive urinary markers in preventing lifestyle-related diseases by comparing lipid metabolism-related parameters with oxidative stress markers in school children.. Subjects were 85 first-grade students. The variables examined included the smoking in subjects' household; exercise habits; height and weight; blood pressure; and plasma total cholesterol, high-density lipoprotein cholesterol, triglyceride, leptin, blood sugar, urinary cotinine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoprostaglandin F2α (IsoP).. Of the subjects, 10.6% were obese (% overweight ≥ 20%), 3.5% had a high-risk arteriosclerosis index (AI; 3 ≤ AI < 5), and 29.4% were passive smokers. No significant differences were seen between boys and girls for any of the measurement parameters. Both urinary 8-OHdG (6.8-24.5 ng/mg creatinine) and IsoP (0.9-7.4 ng/mg creatinine) were detected in all subjects, and a significant positive correlation was seen between the two markers. On multiple regression analysis using AI as an objective variable and all non-invasive markers as explanatory variables, urinary IsoP correlated most strongly with AI (P ≤ 0.01).. Risk factors for atherosclerosis in adults, such as obesity and hypercholesterolemia, are associated with oxidative stress and inflammation. The present findings of the strongest correlation between urinary IsoP and AI suggest that urinary IsoP may serve as a non-invasive and effective early marker in predicting risk in children of developing lifestyle-related diseases.

Topics: Arteriosclerosis; Biomarkers; Child; Dinoprost; Dyslipidemias; Female; Humans; Incidence; Japan; Lipids; Male; Overweight; Oxidative Stress; Risk Assessment; Risk Factors; Schools

The assessment of oxidative stress may aid in the identification of subsequent metabolic risk in obese children. The objective of this study was to determine whether the plasma level of advanced oxidation protein products, analyzed with a recently proposed modified assay that involves a delipidation step (mAOPPs), was related to metabolic risk factors (MRFs) in severely obese children.. The plasma levels of mAOPPs were determined by spectrophotometry in 54 severely obese and 44 healthy children. We also measured lipid peroxidation biomarkers (thiobarbituric acid-reactive substances, malondialdehyde, and 8-isoprotane F(2α)) and sulfhydryl groups, a marker of antioxidant defense. Protein oxidation and lipid peroxidation markers were higher and sulfhydryl levels were lower in obese children compared with controls. Taking metabolic risk into account, obese children were subdivided according to the cutoff point (53.2 μmol/L) obtained for their mAOPPs values from the ROC curve. Anthropometric measures and the existence of hypertension did not differ between groups. The presence of dyslipidemia and insulin resistance was significantly higher in the group with higher mAOPPs levels. The highest levels of mAOPPs were found in the children with ≥3 MRFs. The level of mAOPPs was positively correlated with triglycerides and negatively correlated with high-density lipoprotein cholesterol. There was no correlation of this marker of protein oxidation with biomarkers of lipid peroxidation.. The determination of mAOPPs in delipidated plasma is an easy way to evaluate protein oxidation. It may be useful in severely obese children for better cardiovascular risk assessment.

Topics: Adolescent; Age of Onset; Biomarkers; Chi-Square Distribution; Child; Dinoprost; Dyslipidemias; Female; Humans; Hypertension; Insulin Resistance; Linear Models; Lipid Peroxidation; Lipids; Male; Malondialdehyde; Metabolic Syndrome; Obesity; Oxidation-Reduction; Oxidative Stress; Proteins; Risk Assessment; Risk Factors; Severity of Illness Index; Spain; Spectrophotometry; Sulfhydryl Compounds; Thiobarbituric Acid Reactive Substances; Up-Regulation

The methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymorphism and in non-carriers, in relation to tHcy and folate levels. A cross-sectional comparison of urinary 8-iso-prostaglandin (PG)F(2α) and 11-dehydro-thromboxane (TX)B(2) (markers of in vivo lipid peroxidation and platelet activation, respectively) was performed in 100 carriers and 100 non-carriers of the polymorphism. A methionine-loading test and folic acid supplementation were performed to investigate the causal relationship of the observed associations. Urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) were higher in carriers with hyperhomocysteinaemia than in those without hyperhomocysteinaemia (p<0.0001). Hyperhomocysteinaemic carriers had lower folate levels (p=0.0006), higher urinary 8-iso-PGF(2α) (p<0.0001) and 11-dehydro-TXB(2) (p<0.0001) than hyperhomocysteinaemic non-carriers. On multiple regression analysis, high tHcy (p<0.0001), low folate (p<0.04) and MTHFR 677 C→T polymorphism (p<0.001) independently predicted high rates of 8-iso-PGF(2α) excretion. Methionine loading increased plasma tHcy (p=0.002), and both urinary prostanoid metabolites (p=0.002). Folic acid supplementation was associated with decreased urinary 8-iso-PGF(2α) and 11-dehydro-TXB2 excretion (p<0.0003) in the hyperhomocysteinaemic group, but not in the control group, with substantial inter-individual variability related to baseline tHcy level and the extent of its reduction. In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C→T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation.

Topics: Biomarkers; Cardiovascular Diseases; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus; Dinoprost; Dyslipidemias; Folic Acid; Homocystinuria; Humans; Hyperhomocysteinemia; Lipid Peroxidation; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Muscle Spasticity; Oxidative Stress; Platelet Activation; Polymorphism, Single Nucleotide; Psychotic Disorders; Smoking; Thromboxane B2

Inhibiting the action of proprotein convertase subtilisin/kexin type 9 (PCSK9) on the low-density lipoprotein receptor (LDLR) has emerged as a novel therapeutic target for hypercholesterolemia. Here we investigated the effect of berberine, natural plant extracts, on PCSK9-LDLR pathway in C57BL/6 mice with lipopolysaccharide (LPS) induced inflammation.. Forty female mice were divided into four groups (n =10): control, LPS (5 mg/kg), LPS + berberine 10 (5 mg/kg LPS plus 10 mg/kg berberine), and LPS + berberine 30 (5 mg/kg LPS plus 30 mg/kg berberine). Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; pro-inflammatory cytokines [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)], 8-isoprostane, hepatic expressions of PCSK9 and LDLR were determined.. Berberine pretreatment reduced the expression of hepatic PCSK9, decreased the plasma TC, TG, LDL-C, IFNγ, TNFα, IL-1α, and 8-isoprostane concentrations; increased HDL-C level and LDLR expression in mice.. The present results suggest that berberine inhibits dyslipidemia in C57BL/6 mice with LPS induced inflammation through regulating PCSK9-LDLR pathway.

Topics: Animals; Berberine; Dinoprost; Dyslipidemias; Female; Inflammation; Interferon-gamma; Interleukin-1alpha; Lipids; Lipopolysaccharides; Liver; Mice; Mice, Inbred C57BL; Plant Extracts; Proprotein Convertase 9; Proprotein Convertases; Receptors, LDL; Serine Endopeptidases; Tumor Necrosis Factor-alpha

To evaluate whether oxidative stress is correlated with adiposity, obesity-related metabolic abnormalities, and ambulatory blood pressure (ABP) in a multi-ethnic pediatric population.. We conducted a prospective study enrolling 42 obese children (age, 12.8 ± 2.4 years) and 34 non-obese children (age, 11.8 ± 3.4 years). We measured urine 8-isoprostane and hydrogen peroxide (markers of oxidative stress) in both obese and non-obese groups. In the obese group, we measured the 24-hour ABP and obtained an oral glucose tolerance test, lipid panel, interleukin-6, and tumor necrosis factor-α.. 8-isoprostane and hydrogen peroxide were correlated with body mass index standard deviation score and waist circumference. The mean 8-isoprostane and hydrogen peroxide levels of the obese group were higher than those of the non-obese group. In the subset of obese subjects who underwent ABP monitoring, 8-isoprostane was correlated with mean 24-hour systolic blood pressure: within the obese group, 8-isoprostane was higher in obese children with elevated mean 24-hour systolic blood pressure.. Our findings provide evidence of a significant correlation between oxidative stress, adiposity, and blood pressure in children. Longitudinal studies in a larger population sample are needed to validate the association between elevated urine 8-isoprostane level and cardiovascular risk factors in an obese pediatric population.

Topics: Adolescent; Child; Cross-Sectional Studies; Dinoprost; Dyslipidemias; Female; Humans; Hydrogen Peroxide; Hypertension; Interleukin-6; Male; Obesity; Oxidative Stress; Prospective Studies; Tumor Necrosis Factor-alpha

The key roles that obesity, hyperglycemia, hyperlipidemia, inflammation, and oxidative stress play in the progression of diabetes vascular complications are well recognized; however, the relative contribution and importance of these individual factors remain uncertain. At 6, 10, or 14 weeks old, blood samples and thoracic aortae were collected from db/db mice and their non-diabetic controls. Plasma samples were analyzed for glucose, 8-isoprostane, CRP, triglycerides, LDL, and HDL as markers of glycemic status, oxidative stress, inflammation, and dyslipidemia, respectively. The responses of the aortic rings to high KCl, phenylephrine (PE), acetylcholine (ACh), and sodium nitroprusside were examined. Statistical methods were used to estimate the strength of the association between plasma variables and vascular functions. Systemic inflammation occurred in db/db mice at an earlier age than did hyperglycemia or oxidative stress. Aortae of db/db showed augmented contractions to PE which were positively correlated with weight, plasma glucose, 8-isoprostane, and CRP. Also, db/db mice showed impaired endothelium-dependent ACh vasorelaxation which was negatively correlated with weight, plasma glucose, and 8-isoprostane. Multivariate analysis and stepwise modeling show that CRP is the major determinant of the contractile responses, while weight and HDL are the major determinants of ACh-induced relaxation. Among the traditional risk factors of obesity, hyperglycemia, oxidative stress, inflammation, and dyslipidemia, our study reveals that weight and inflammation are the major determinants of vascular dysfunction in the aortae of db/db mice. Our findings partially resolve the complexity of diabetes vasculopathies and suggest targeting weight loss and inflammation for effective therapeutic approaches.

Topics: Animals; Aorta; Biomarkers; Blood Glucose; Body Weight; C-Reactive Protein; Diabetes Mellitus, Experimental; Dinoprost; Dyslipidemias; Inflammation; Lipids; Male; Mice; Mice, Inbred Strains; Multivariate Analysis; Oxidative Stress; Vasodilation

The precise role of the nitric oxide synthase (NOS) system in lipid metabolism remains to be elucidated. We addressed this point in mice that we have recently developed and that lack all three NOS isoforms.. Wild-type (WT), singly, doubly, and triply NOS(-/-) mice were fed either a regular or high-cholesterol diet for 3-5 months. The high-cholesterol diet significantly increased serum low-density lipoprotein (LDL) cholesterol levels in all the genotypes when compared with the regular diet. Importantly, when compared with the WT genotype, the serum LDL cholesterol levels in the high-cholesterol diet were significantly and markedly elevated only in the triply NOS(-/-) genotype, but not in any singly or doubly NOS(-/-) genotypes, and this was associated with remarkable atherosclerosis and sudden cardiac death, which occurred mainly in the 4-5 months after the high-cholesterol diet. Finally, hepatic LDL receptor expression was markedly reduced only in the triply NOS(-/-) genotype, accounting for the diet-induced dyslipidaemia in the genotype.. These results provide the first direct evidence that complete disruption of all NOS genes causes severe dyslipidaemia, atherosclerosis, and sudden cardiac death in response to a high-fat diet in mice in vivo through the down-regulation of the hepatic LDL receptor, demonstrating the critical role of the whole endogenous NOS system in maintaining lipid homeostasis.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Biomarkers; Blood Pressure; C-Reactive Protein; Cholesterol, Dietary; Cholesterol, LDL; Death, Sudden, Cardiac; Dinoprost; Disease Models, Animal; Dyslipidemias; Genotype; Liver; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Phenotype; Receptors, LDL; Severity of Illness Index; Sterol Regulatory Element Binding Protein 2; Time Factors