8-hydroxy-2--deoxyguanosine and Metabolic-Syndrome

Metabolic syndrome (MetS) refers to clustered cardiovascular risk factors (abdominal obesity, pre-diabetes, high blood pressure, dyslipidaemia). Therapies targeting oxidative stress may delay progression to atherosclerosis and diabetes. We investigated the anti-oxidative effect of a supplement combining red yeast rice and olive extract in patients with MetS.. A double-blind, placebo-controlled, randomised trial was conducted with 50 patients with MetS as defined by National Cholesterol Education Program Adult Treatment Panel III criteria. Forty-nine subjects randomly assigned to red yeast rice-olive extract (RYR-olive extract; 10.82 mg of monacolins and 9.32 mg of hydroxytyrosol per Cholesfytolplus capsule) or placebo completed the 8-week trial. Whereas effects on cardiovascular risk parameters of MetS have been reported recently, the observed significant 20% increase in oxidised low-density lipoprotein (OxLDL) prompted us to investigate other oxidative stress-related parameters: malondialdehyde (MDA), lipoprotein-associated phospholipase A. The updated results indicate that an RYR-olive extract supplement significantly reduced Lp-PLA. RYR-olive extract significantly reduced Lp-PLA. ClinicalTrials.gov identifier: NCT02065180 . Registered on 13 February 2014.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Belgium; Biological Products; Biomarkers; Deoxyguanosine; Dietary Supplements; Double-Blind Method; Female; Humans; Linear Models; Lipoproteins, LDL; Male; Malondialdehyde; Metabolic Syndrome; Multivariate Analysis; Olea; Oxidative Stress; Plant Extracts; Time Factors; Treatment Outcome

Background. Oxidative stress is increasingly important in health research. Therefore, it is necessary to understand which factors determine basal oxidative stress. This study examines the associations of various determinants with markers of oxidative DNA and lipid damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostanes. Methods. Data are from the Netherlands Study of Depression and Anxiety; 1117 subjects (18-65 years) without a current psychiatric diagnosis. Multivariable regression analyses were conducted with plasma levels of 8-OHdG and F2-isoprostanes (measured by LC/MS-MS) including sociodemographic, lifestyle, and sampling variables. Associations with metabolic syndrome (MetS) and chronic disease were examined. Results. 8-OHdG and F2-isoprostanes were weakly correlated (r = 0.06, p = 0.045). Both were positively associated with age and cotinine (cigarette exposure); 8-OHdG was lower in females and after longer sample storage. F2-isoprostanes were higher in females, alcohol users, and in samples collected in spring and lower in supplement users and those with more education. Both markers were lower in fasting subjects. F2-isoprostanes, not 8-OHdG, were positively associated with MetS. Conclusion. The weak correlation between 8-OHdG and F2-isoprostanes suggests they reflect specific aspects of oxidative stress. Both markers are associated with a range of sociodemographic, lifestyle, and sampling determinants which should be considered in future research. F2-isoprostanes are associated with MetS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Deoxyguanosine; Fasting; Female; Humans; Isoprostanes; Life Style; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Socioeconomic Factors

Metabolic syndrome (MetS), in which a non-classic feature is an increase in systemic oxidative biomarkers, presents a high risk of diabetes and cardiovascular disease (CVD). Adherence to the Mediterranean Diet (MedDiet) is associated with a reduced risk of MetS. However, the effect of the MedDiet on biomarkers for oxidative damage has not been assessed in MetS individuals. We have investigated the effect of the MedDiet on systemic oxidative biomarkers in MetS individuals.. Randomized, controlled, parallel clinical trial in which 110 female with MetS, aged 55-80, were recruited into a large trial (PREDIMED Study) to test the efficacy of the traditional MedDiet on the primary prevention of CVD. Participants were assigned to a low-fat diet or two traditional MedDiets (MedDiet + virgin olive oil or MedDiet + nuts). Both MedDiet group participants received nutritional education and either free extra virgin olive oil for all the family (1 L/week), or free nuts (30 g/day). Diets were ad libitum. Changes in urine levels of F2-Isoprostane (F2-IP) and the DNA damage base 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) were evaluated at 1-year trial.. After 1-year urinary F2-IP decreased in all groups, the decrease in MedDiet groups reaching a borderline significance versus that of the Control group. Urinary 8-oxo-dG was also reduced in all groups, with a higher decrease in both MedDiet groups versus the Control one (P < 0.001).. MedDiet reduces oxidative damage to lipids and DNA in MetS individuals. Data from this study provide evidence to recommend the traditional MedDiet as a useful tool in the MetS management.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Deoxyguanosine; Diet, Fat-Restricted; Diet, Mediterranean; DNA Damage; F2-Isoprostanes; Female; Humans; Lipid Metabolism; Metabolic Syndrome; Middle Aged; Nuts; Olive Oil; Oxidative Stress; Plant Oils; Risk Factors; Risk Reduction Behavior

Oxidative stress has a key role in atherosclerosis, cancer and other chronic diseases. Some bioactive compounds in nuts have been implicated in antioxidant activities.. We assessed how nut consumption affected several markers of oxidation and endothelial function (EF) in metabolic syndrome (MetS) patients.. A randomized, controlled, parallel feeding trial was conducted on 50 MetS adults who were recommended a healthy diet supplemented or not with 30 g of mixed nuts (Nut and Control groups, respectively) every day for 12 weeks. The plasma antioxidant capacity (AC), oxidized LDL (oxLDL), conjugated diene (CD) formation, urine 8-isoprostanes, DNA damage assessed by yield of urine 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), and EF assessed by peripheral artery tonometry (PAT) and biochemical markers, were measured at baseline and the end of the intervention.. No significant differences in changes between groups were observed in AC, oxLDL, CD, 8-isoprostanes or EF during the intervention, whereas the reduction in DNA damage was significant in the Nut group compared to Control group (P < 0.001).. Nut consumption has no deleterious effect on lipid oxidation. The decrease in DNA damage observed in this study could contribute to explain the beneficial effects of regular nut consumption on some MetS features and several chronic diseases.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Antioxidants; Arteries; Biomarkers; Deoxyguanosine; Diet; DNA Damage; Endothelium, Vascular; Fatty Acids, Unsaturated; Humans; Isoprostanes; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Nuts; Oxidative Stress; Vascular Resistance; Young Adult

Arterial dysfunction is a hallmark of early atherosclerosis; however, its behavior in patients with metabolic syndrome (MS) is still unclear. We investigated the role of oxidative stress on ischemia-induced flow-mediated dilatation (FMD) in patients with MS. FMD and oxidative stress, as assessed by serum levels of 8-hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), were studied in 18 MS and 30 control subjects. Thereafter, in the 18 MS patients, FMD was assessed after iv infusion of 1 g vitamin C or placebo in a randomized, double-blind, crossover design; serial blood samples were taken in peripheral circulation before and after FMD to analyze 8-OHdG. Compared to controls, MS patients had higher 8-OHdG (p<0.001) and lower FMD (p<0.001); 8-OHdG and FMD were inversely correlated (R=-0.74; p<0.01). In MS patients, placebo administration did not change FMD, whereas vitamin C significantly enhanced it (p<0.001). After placebo, ischemia-induced FMD was associated with a significant increase in 8-OHdG (p<0.001), an effect that was counteracted by vitamin C. Vitamin C infusion was associated with an inverse correlation between the changes in FMD and oxidative stress (R=-0.67; p<0.01). The present study shows that arterial dilatation is impaired and that enhanced oxidative stress may play a key role in patients with MS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Arteries; Ascorbic Acid; Cross-Sectional Studies; Deoxyguanine Nucleotides; Humans; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress

Adult growth hormone deficiency (GHD) is being increasingly recognized to cause premature mortality exacerbated by oxidative stress. A case-control observational study has been performed with the primary objective of evaluating new parameters of oxidative stress and macromolecular damage in adult GHD subjects: serum nitrotryptophan; Total Antioxidant Capacity expressed as LAG time; urinary hexanoil-lysine; urinary dityrosine and urinary 8-OH-deoxyguanosine. GHD was diagnosed using Growth Hormone-Releasing Hormone 50μg iv+arginine 0,5 g/Kg test, with a peak GH response <9 μg /L when BMI was <30 kg/m2 or <4 μg/L when BMI was >30 kg/m2. Patients affected by adult GHD were divided into three groups, total GHD (n = 26), partial GHD (n = 25), and controls (n = 29). Total Antioxidant Capacity, metabolic and hormonal parameters have been determined in separate plasma samples; nitrotryptophan in serum samples; hexanoil-lysine, dityrosine, 8-OH-deoxyguanosine in urine samples. Assessment of hexanoil-lysine exhibited a trend to increase in comparing total GHD vs partial and controls, although not significant. Values of 8-OH-deoxyguanosine did not significantly differ among the three groups. Significant lower levels of dityrosine in partial GHD vs total and controls were found. No significant difference in nitrotriptophan serum levels was found, while significantly greater values of Total Antioxidant Capacity were showed in total and partial GHD vs controls. Thus, our result confirm that oxidative stress is increased both in partial and total adult GHD. The lack of compensation by antioxidants in total GHD may be connected to the complications associated to this rare disorder.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Arnold-Chiari Malformation; Biomarkers; Case-Control Studies; Empty Sella Syndrome; Female; Human Growth Hormone; Humans; Hypopituitarism; Lipid Peroxidation; Lysine; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Tryptophan; Tyrosine

The role of homocysteine (Hcy) and associated oxidative stress processes in the metabolic syndrome (MetS) continuum has not been explored extensively. Changes in Hcy and associated oxidative stress in relation to the number of metabolic syndrome factors present are explored in this study.. Participants (n=266) attending a rural diabetes screening clinic had their medical history recorded as well as body mass index, Hcy, glucose, cholesterol, glutathione (GSH), and 8-hydroxy-2-deoxyguanosine (8-OHdG) measured.. A significant elevation in Hcy (9.5μmol/L ±2 vs. 10.6μmol/L ±3, p=0.03) and 8-OHdG (307pg/mL ±516 vs. 1130pg/mL ±1155, p=0.0001) was observed between the noMetS and MetS groups. Hcy increased with the addition of MetS factors paralleled by 8-OHdG and GSH. A dramatic increase was seen in 8-OHdG, nearly doubling between 2 MetS and 3 MetS factors present (p=0.0001).. Homocysteine may be a useful marker together with 8-OHdG in assessing the extent of metabolic syndrome in a rural population.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Case-Control Studies; Deoxyguanosine; Female; Glutathione; Homocysteine; Humans; Interleukin-6; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress

For appropriate sepsis care, prognostic laboratory markers are mandatory. The aim of our study was to evaluate the predictive value of serum actin, gelsolin and the recently defined actin/gelsolin ratio during sepsis by comparison it to classical clinical and inflammatory laboratory parameters.. We analyzed sera of severe septic (n=32) and SIRS (n=12) patients for 5days. Ophthalmologic patients (n=27) served as controls. Besides serum actin, gelsolin and actin/gelsolin ratios classical laboratory parameters (WBC count, serum procalcitonin, hsCRP) and clinical scores (APACHE II, SAPS II, SOFA), were also assessed.. Septic patients showed significantly decreased first-day gelsolin levels and increased actin/gelsolin ratios compared to SIRS patients (p<0.05), furthermore, non-survivors had significantly lower gelsolin levels compared to survivors (p<0.05). Non-survivors had 11.4-fold higher 2nd day actin/gelsolin ratios than survivors. Besides procalcitonin (PCT) and hsCRP, gelsolin and actin/gelsolin ratios also proved to be useful in discriminating SIRS from sepsis in the ICU (p<0.05). Gelsolin had similar prognostic value to PCT when assessing 7-day mortality and the predictive capacity of the first-day actin/gelsolin ratios was similar to that of APACHE II score regarding ICU mortality in severe sepsis.. Serum gelsolin and actin/gelsolin ratio might serve as efficient complementary prognostic markers in sepsis. However, for daily clinical usage, an automated laboratory assay of actin and gelsolin is still needed to be developed.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Actins; Aged; Deoxyguanosine; Female; Gelsolin; Glutathione; Homocysteine; Humans; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Sepsis

Metabolic syndrome describes a group of clinical features that together increase the incidence of coronary artery disease, stroke and type 2 diabetes. Insulin resistance is a major risk factor for developing metabolic syndrome. A chronic state of inflammation accompanies the accumulation of surplus lipids in adipose and liver tissue, frequently involved in insulin resistance. 8-Oxo-2'-deoxyguanosine (8-Oxo-dG) is a potent anti-inflammatory agent that inactivates both Rac1 and Rac2 which are critical to initiating the inflammatory responses in various cell types, including macrophages. In this study, we explored whether 8-Oxo-dG suppressed a series of systemic inflammatory cascades, resulting in the amelioration of typical features of metabolic syndrome in obese mice. The results demonstrate that 8-Oxo-dG effectively improved hyperglycemia, dyslipidemia and fatty liver changes in obese mice. The level of biochemical markers indicative of systemic inflammation were reduced in 8-Oxo-dG treated mice, whereas serum levels of adiponectin, a crucial factor associated with improved metabolic syndrome, were enhanced. Our results demonstrate that 8-Oxo-dG effectively disrupts the pathogenesis of insulin resistance and obesity-associated metabolic syndrome.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cytokines; Deoxyguanosine; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Treatment Outcome

Experiments determined whether the combination of endothelin A (ETA) receptor antagonist [ABT-627, atrasentan; (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid] and a thiazide diuretic (chlorthalidone) would be more effective at lowering blood pressure and reducing renal injury in a rodent model of metabolic syndrome compared with either treatment alone. Male Dahl salt-sensitive rats were fed a high-fat (36% fat), high-salt (4% NaCl) diet for 4 weeks. Separate groups of rats were then treated with vehicle (control), ABT-627 (ABT; 5 mg/kg per day, in drinking water), chlorthalidone (CLTD; 5 mg/kg per day, in drinking water), or both ABT plus CLTD. Mean arterial pressure (MAP) was recorded continuously by telemetry. After 4 weeks, both ABT and CLTD severely attenuated the development of hypertension, whereas the combination further reduced MAP compared with ABT alone. All treatments prevented proteinuria. CLTD and ABT plus CLTD significantly reduced nephrin (a podocyte injury marker) and kidney injury molecule-1 (a tubulointerstitial injury marker) excretion. ABT, with or without CLTD, significantly reduced plasma 8-oxo-2'-deoxyguanosine, a measure of DNA oxidation, whereas CLTD alone had no effect. All treatments suppressed the number of ED1(+) cells (macrophages) in the kidney. Plasma tumor necrosis factor receptors 1 and 2 were reduced only in the combined ABT and CLTD group. These results suggest that ABT and CLTD have antihypertensive and renal-protective effects in a model of metabolic syndrome that are maximally effective when both drugs are administered together. The findings support the hypothesis that combined ETA antagonist and diuretic treatment may provide therapeutic benefit for individuals with metabolic syndrome consuming a Western diet.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Arterial Pressure; Atrasentan; Cell Adhesion Molecules; Chlorthalidone; Deoxyguanosine; Disease Models, Animal; Diuretics; Drug Combinations; Endothelin A Receptor Antagonists; Endothelins; Hypertension; Inflammation; Kidney Diseases; Male; Membrane Proteins; Metabolic Syndrome; Oxidative Stress; Proteinuria; Pyrrolidines; Rats; Rats, Inbred Dahl; Rats, Sprague-Dawley; Receptor, Endothelin A; Sodium Chloride, Dietary

Low vitamin B-6 status has been linked to an increased risk of cardiovascular diseases. The cardioprotective effects of vitamin B-6 independent of homocysteine suggest that additional mechanisms may be involved.. Our objective was to examine the cross-sectional association of vitamin B-6 status with markers of inflammation and oxidative stress.. We measured plasma pyridoxal-5'-phosphate (PLP), C-reactive protein (CRP), and an oxidative DNA damage marker, urinary 8-hydroxydeoxyguanosine (8-OHdG), in Puerto Rican adults who were living in Massachusetts (n = 1205, aged 45-75 y).. There was a strong dose-response relation of plasma PLP concentration with plasma CRP. Increasing quartiles of PLP were significantly associated with lower CRP concentrations (geometric means: 4.7, 3.6, 3.1, and 2.5 mg/L; P for trend < 0.0001) and with lower urinary 8-OHdG concentrations (geometric means: 124, 124, 117, and 108 ng/mg creatinine; P for trend: 0.025) after multivariate adjustment. These negative associations persisted after plasma homocysteine was controlled for. Plasma PLP concentrations were significantly correlated with plasma fasting glucose (r = -0.1, P = 0.0006), glycated hemoglobin (r = -0.08, P = 0.006), and homeostasis model assessment of beta cell function (r = 0.082, P = 0.005). Metabolic syndrome, obesity, and diabetes were also significantly associated with low plasma PLP concentrations (P = 0.011, 0.0007, and 0.004, respectively).. Low vitamin B-6 concentrations are associated with inflammation, higher oxidative stress, and metabolic conditions in older Puerto Rican adults. Our data suggest that vitamin B-6 may influence cardiovascular disease risk through mechanisms other than homocysteine and support the notion that nutritional status may influence the health disparities present in this population.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Boston; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Deoxyguanosine; Female; Hispanic or Latino; Humans; Inflammation; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Pyridoxal Phosphate; Statistics, Nonparametric; Vitamin B 6

Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to reduce the intestinal absorption of cholesterol. We investigated whether it also has beneficial effects on metabolic disorder and/or renal insufficiency in patients with hypercholesterolemia.. Ezetimibe was administered to 38 Japanese patients with hypercholesterolemia to obtain appropriate low-density lipoprotein cholesterol (LDL-chol) levels. Age- and sex-matched patients with hypercholesterolemia (n=38) were the controls. We evaluated the effects of ezetimibe before and 4 to 8 weeks after ezetimibe treatment.. Ezetimibe significantly decreased LDL-chol levels and metabolic syndrome-related factors, including body weight, waist circumference, blood pressure; homeostasis model assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were significantly reduced. In addition, it decreased the level of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and increased the urinary excretion of nitrate and nitrite (NOx). In the controls we observed no such changes. Excepting the decrease in the serum TNF-alpha level, the effects of ezetimibe were not correlated with decreased LDL-chol levels.. Ezetimibe ameliorated the status of metabolic syndrome and microalbuminuria, reduced inflammation and oxidative stress, and increased nitric oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Albuminuria; Anticholesteremic Agents; Azetidines; C-Reactive Protein; Case-Control Studies; Cholesterol, LDL; Deoxyguanosine; Ezetimibe; Female; Humans; Hypercholesterolemia; Male; Metabolic Diseases; Metabolic Syndrome; Middle Aged; Nitrates; Nitrites; Oxidative Stress; Tumor Necrosis Factor-alpha

We have demonstrated previously that both acute and chronic oral administration of adenosine have novel functions such as anti-hypertensive effects and improved hyperlipidaemia in stroke-prone spontaneously hypertensive rats (SHRSP) fed a normal diet. The purpose of the present study was to investigate the effect of adenosine administration on metabolic syndrome-related parameters in SHRSP fed a high-fat diet. Six-week-old rats were divided into three groups, and were administered either water (control) or adenosine (10 or 100 mg/l) for 8 weeks. During this period, the rats had free access to a high-fat diet based on AIN-93M. The results showed that hypertension, plasma lipid, NO, insulin, glucose and urinary 8-hydroxy-2'-deoxyguanosine levels improved significantly in both adenosine groups. The mRNA expression levels of genes involved in anti-oxidative activity and adenosine receptors were also altered in the adenosine groups. Administration of adenosine also increased plasma adiponectin levels, accompanied by upregulation of mRNA expression level of adiponectin and adiponectin receptor 1 in perirenal fat and adiponectin receptor 2 in the liver. In conclusion, oral administration of adenosine is effective for improving metabolic syndrome-related parameters in SHRSP, and accordingly it may prevent the progression of the metabolic syndrome.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenosine; Adiponectin; Adipose Tissue; Animals; Antioxidants; Blood Glucose; Cardiovascular Agents; Deoxyguanosine; Dietary Fats; Enzymes; Gene Expression; Gene Expression Regulation; Hypertension; Insulin; Kidney; Lipids; Liver; Male; Metabolic Syndrome; Nitric Oxide; Rats; Rats, Inbred SHR; Receptors, Adiponectin; RNA, Messenger; Stroke

It is well known that oxidative stress is induced by metabolic syndrome (MetS), leading to cardiovascular diseases. On the other hand, obstructive sleep apnea syndrome (OSAS) is frequently complicated with MetS, and OSAS is also considered to induce oxidative stress. Thus, we examined the plasma and urine markers of oxidative stress and antioxidant status in patients with OSAS with or without MetS.. Sixty-nine Japanese men suspected of having OSAS were recruited. We divided all patients into 3 groups: nonobese patients, obese patients without MetS, and patients with MetS. Oxidative stress markers, plasma and urine 8-hydroxydeoxyguanosine (8-OHdG) and plasma N epsilon-(hexanoyl) lysine (HEL), and an antioxidant status marker, plasma total antioxidant status, were measured by enzyme-linked immunosorbent assay.. The plasma HEL level was significantly increased in patients with MetS, whereas neither plasma and urine 8-OHdG levels nor plasma total antioxidant status level was different in patients with MetS. Furthermore, the plasma HEL level was significantly and positively correlated with fasting plasma glucose, serum insulin, and homeostasis model assessment-insulin resistance index in all subjects.. The oxidative stress is strongly associated with the presence of MetS but not related to the presence or severity of OSAS. Furthermore, we demonstrated that the plasma concentration of HEL is a more sensitive biomarker of oxidative stress in patients with MetS than the plasma and urine levels of 8-OHdG.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Biomarkers; Deoxyguanosine; Humans; Lysine; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Sleep Apnea, Obstructive

Traffic-related air pollution is associated with cardiovascular morbidity and mortality. Although the biological mechanisms are not well understood, oxidative stress may be a primary pathway. Subpopulations, such as individuals with metabolic syndrome (MeS), may be at increased risk of adverse effects associated with air pollution. Our aim was to assess the relationship between exposure to diesel exhaust (DE) and indicators of systemic antioxidant and oxidative responses in adults with MeS. We hypothesized that DE exposure would result in greater oxidative stress and antioxidant responses compared with filtered air (FA).. Ten adult subjects with MeS were exposed on separate days for two hours to FA or DE (at 200microg/m3), in a double blind, crossover experiment. Urinary 8-isoPGF2alpha (F2-isoprostanes), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were assessed as markers of oxidative stress at 3 hrs and 22 hrs, respectively, after exposure initiation. To assess the short-term antioxidant response we analyzed plasma ascorbic acid (AA) 90 minutes after exposure initiation. All outcomes were compared to pre-exposure levels, and mean changes were compared between FA and DE exposures.. Mean changes in urinary F2-isoprostanes (ng/mg creatinine), (-0.05 [95% CI = -0.29, 0.15]), and 8-OHdG (microg/g creatinine) (-0.09 [-0.13, 0.31]), were not statistically significant. Mean changes in plasma AA (mg/dl) were also not significant (-0.02 [-0.78, 0.04]).. In this carefully controlled experiment, we did not detect significant changes in oxidative stress or systemic antioxidant responses in subjects with MeS exposed to 200microg/m3 DE.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Age Factors; Antioxidants; Ascorbic Acid; Biomarkers; Creatinine; Cross-Over Studies; Deoxyguanosine; Double-Blind Method; F2-Isoprostanes; Female; Follow-Up Studies; Humans; Inhalation Exposure; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Vehicle Emissions; Young Adult

Metabolic syndrome (MetS) is a group of cardiovascular risk factors, including visceral obesity, glucose intolerance, hypertension, and dyslipidemia. Increased oxidative and nitrative stress and inflammation and decreased endothelial function occur in an animal model of metabolic syndrome, SHR/NDmcr-cp (SHR/cp) rats. The present study investigated the effects of coenzyme Q10 (CoQ10), one of the important antioxidants, on the abnormal oxidative condition and characteristic components of metabolic syndrome in SHR/cp rats by maintaining them on a diet supplemented with 0.07% - 0.7% CoQ10 for 26 weeks. We determined serum levels of oxidatively modified low-density lipoprotein (Ox-LDL) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as oxidative stress markers, 3-nitrotyrosine as a nitrative stress marker, 3-chlorotyrosine as a marker of myeloperoxidase (MPO)-catalyzed oxidation and high-sensitivity C-reactive protein (hsCRP) as an inflammatory marker. The administration of CoQ10 significantly attenuated the increase of oxidative and nitrative stress markers and inflammatory markers in a dose-dependent manner. CoQ10 prevented the elevated serum insulin levels, although it did not affect the elevated glucose level and dyslipidemia. CoQ10 also reduced elevated blood pressure, but did not affect body weight gain. In addition, CoQ10 improved endothelial dysfunction in the mesenteric arteries. These findings suggest that the antioxidant properties of CoQ10 can be effective for ameliorating cardiovascular risk in MetS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Body Weight; Deoxyguanosine; Disease Models, Animal; Inflammation; Insulin; Lipids; Lipoproteins, LDL; Metabolic Syndrome; Oxidative Stress; Peroxidase; Rats; Rats, Inbred SHR; Tyrosine; Ubiquinone

Corosolic acid (CRA), a constituent of banaba leaves, has been reported to have anti-inflammatory and hypoglycemic activities. The aim of this study was to determine the effects of CRA on metabolic risk factors including obesity, hypertension, hyperinsulinemia, hyperglycemia, and hyperlipidemia together with oxidative stress and inflammation, all of which are characteristic of the SHR/NDmcr-cp (cp/cp) (SHR-cp) rat, an animal model of metabolic syndrome. Six-week-old male SHR-cp rats were fed a high fat diet containing 0.072% CRA for 14 weeks. Treatment with CRA lowered blood pressure, which was elevated in control animals, by 10% after 8 weeks, and serum free fatty acids by 21% after 2 weeks. CRA treatment resulted in decreases in the levels of the oxidative stress markers thiobarbituric acid-reactive substances and 8-hydroxydeoxyguanosine by 27% and 59%, respectively, after 2 weeks. CRA treatment also reduced the levels of myeloperoxidase markers, 3-nitrotyrosine and 3-chlorotyrosine by 38% and 39%, respectively, after 10 weeks, and tended to decrease the levels of high sensitivity C-reactive protein, a marker of inflammation, after 6 weeks. However, CRA had no effect on weight gain or hyperglycemia. These results demonstrate that CRA can ameliorate hypertension, abnormal lipid metabolism, and oxidative stress as well as the inflammatory state in SHR-cp rats. This implies that CRA can be beneficial for preventing atherosclerosis-related diseases that are an increasing health care problem worldwide.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Deoxyguanosine; Disease Models, Animal; Fatty Acids, Nonesterified; Hypertension; Inflammation; Insulin; Male; Metabolic Syndrome; Molecular Structure; Musa; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Inbred SHR; Thiobarbituric Acid Reactive Substances; Triglycerides; Triterpenes; Tyrosine