Antioxidant activity from extra virgin olive oil via inhibition of hydrogen peroxide-mediated NADPH-oxidase 2 activation.

OBJECTIVES: Extra virgin olive oil (EVOO) supplementation is associated with a significant reduction in cardiovascular disease but the underlying mechanism is still unclear. METHODS: In platelets that were taken from healthy subjects (n = 5), agonist-induced hydrogen peroxide (H2O2) production and NADPH oxidase 2 (NOX2) activation in the presence of or without catalase, which catabolizes H2O2, were investigated. Platelet H2O2 production, NOX2 activation, EVOO vitamin E, and total polyphenols as well as EVOO's ability to scavenge H2O2 were also measured. RESULTS: Platelet NOX2 activation and H2O2 production were significantly inhibited in catalase-treated platelets and platelets that were incubated with five different EVOOs. The EVOO content of vitamin E was 53 to 223 mg/kg and total polyphenols 145 to 392 mg/L Gallic acid equivalent. EVOOs quenched in vitro H2O2 by 39 to 62%, which is an effect that is significantly correlated with vitamin E and total polyphenol concentrations (R = 0.688; P <0.001 and R = 0.541; P <0.001, respectively). CONCLUSIONS: This in vitro study provides the first evidence that EVOO downregulates platelet H2O2 and in turn NOX2 activity via H2O2 scavenging.

Extra virgin olive oil improves post-prandial glycemic and lipid profile in patients with impaired fasting glucose.

BACKGROUND & AIMS: Extra virgin olive oil (EVOO) improves post-prandial glycaemia in healthy subjects but it has never been investigated if this can be detected in pre-diabetic patients. We investigated if EVOO affects post-prandial glucose and lipid profile in patients with impaired fasting glucose (IFG). METHODS: Thirty IFG patients were randomly allocated to a meal containing or not 10 g of EVOO in a cross-over design. Before, 60 min and 120 min after lunch a blood sample was taken to measure glucose, insulin, Glucagon-like peptide-1 (GLP1), dipeptidyl-peptidase-4 (DPP4) activity, triglycerides (TG), total cholesterol, HDL-cholesterol and Apo B-48. RESULTS: The meal containing EVOO was associated with a reduction of glucose (p = 0.009) and DPP4 activity (p < 0.001) and a significant increase of insulin (p < 0.001) and GLP-1 (p < 0.001) compared with the meal without EVOO. Furthermore, the meal containing EVOO showed a significant decrease of triglycerides (p = 0.002) and Apo B-48 (p = 0.002) compared with the meal without EVOO. Total cholesterol and HDL cholesterol levels did not significantly change between the two groups. CONCLUSIONS: This is the first study to show that in IFG patients EVOO improves post-prandial glucose and lipid profile with a mechanism probably related to incretin up-regulation.

Role of NOX2 in mediating doxorubicin-induced senescence in human endothelial progenitor cells.

Senescence exerts a great impact on both biological and functional properties of circulating endothelial progenitor cells (EPCs), especially in cardiovascular diseases where the physiological process of aging is accelerated upon clinical administration of certain drugs such as doxorubicin. EPC impairment contributes to doxorubicin-induced cardiotoxicity. Doxorubicin accelerates EPC aging, although mechanisms underlying this phenomenon remain to be fully clarified. Here we investigated if Nox2 activity is able to modulate the premature senescence induced in vitro by doxorubicin in human EPCs. Results showed that in conditioned media obtained from late EPC cultures, the levels of interleukin-6, isoprostanes and nitric oxide bioavailability were increased and reduced respectively after 3h of doxorubicin treatment. These derangements returned to physiological levels when cells were co-treated with apocynin or gp91ds-tat (antioxidant and specific Nox2 inhibitors, respectively). Accordingly, Nox2 activity resulted to be activated by doxorubicin. Importantly, we found that Nox2 inhibition reduced doxorubicin-induced EPC senescence, as indicated by a lower percentage of ß-gal positive EPCs. In conclusion, Nox2 activity efficiently contributes to the mechanism of oxidative stress-induced increase in premature aging conferred by doxorubicin. The importance of modulation of Nox2 in human EPCs could reveal a useful tool to restore EPC physiological function and properties.

Extra virgin olive oil phenols suppress migration and invasion of T24 human bladder cancer cells through modulation of matrix metalloproteinase-2.

The consumption of extra virgin olive oil (EVOO), a common dietary habit of the Mediterranean people, seems to be related to a lower incidence of certain types of cancer including bladder neoplasm. Metastases are the major cause of bladder cancer-related deaths and targeting cell motility has been proposed as a therapeutic strategy to prevent cancer spread. This study aimed to investigate the potential antimetastatic effect of total phenols extracted from EVOO against the human transitional bladder carcinoma cell line T24. We also aimed at verifying that EVOO extract exerts cytotoxic effect on tumor cells without affecting normal urothelial fibroblasts. Our results show that EVOO extract can significantly inhibit the proliferation and motility of T24 bladder cells in a dose-dependent manner. In the same experimental conditions fibroblast proliferation and motility were not significantly modified. Furthermore the enzymatic activity of MMP-2 was inhibited at nontoxic EVOO extract doses only in T24 cells. The qRT-PCR revealed a decrease of the MMP-2 expression and a simultaneous increase of the tissue inhibitors of metalloproteinases expression. Our results may support the epidemiological evidences that link olive oil consumption to health benefits and may represent a starting point for the development of new anticancer strategies.

The relationship between metabolic syndrome, its components, and the whole-body atherosclerotic disease burden as measured by computed tomography angiography.

OBJECTIVE: Quantify the whole-body atherosclerotic disease in asymptomatic subjects with and without metabolic syndrome (MetS) and to assess the contribution of the syndrome and its components to the atherosclerotic burden. METHODS: Sixty-five subjects with and 51 without ATPIII-defined MetS underwent a 64-slice computed tomography angiography (CTA). Plaques causing >0% stenosis in coronary or extra-coronary arteries were classified as positive. RESULTS: The prevalence of plaques in coronary, carotid and peripheral arteries as well as their severity did not differ between groups. Conversely, it was seen an almost 3-fold increased likelihood (OR=2.70; 95% CI 1.30-5.57; P<0.001) of atherosclerosis in any district across categories of MetS components (0-1 vs. 2-3 vs. 4-5). Hypertriglyceridemia (P<0.05) and high blood glucose (P<0.05) were independent predictors of the atherosclerotic burden. CONCLUSIONS: Atherosclerotic burden as revealed by 64-TCA appears to be more strongly associated with the number of MetS-related factors than to the clinical diagnosis of MetS itself.

Vitamin E and enzymatic/oxidative stress-driven oxysterols in amnestic mild cognitive impairment subtypes and Alzheimer's disease.

Oxidative stress,which contributes to neuronal damage, is thought to be a pathophysiologicalmechanism of Alzheimer's disease (AD). Markers of oxidative stress may appear early in the preclinical, mild cognitive impairment (MCI) phase of AD.We investigated the interaction among enzymatic-derived oxysterols (24S-hydroxycholesterol and 27-hydroxycholesterol), markers of oxidative stress, including free radical-related oxysterols (7 hydroxycholesterol and 7-ketocholesterol), and vitamin E in AD patients and two amnestic MCI subtypes, amnestic single-domain MCI (a-MCI) subjects, and multidomain MCI (md-MCI) subjects, compared to healthy control subjects (HC). The study included 37 patients with AD, 24 with a-MCI, 29 with md-MCI, and 24 HC. Plasma assessments were made using isotope dilution-mass spectrometry. Although we found no significant change in free radical- or enzymatic-derived oxysterol concentrations in AD or MCI patients, vitamin E levels corrected for cholesterol were reduced in AD patients compared to HC. Results suggest that AD patients have upregulated cerebral oxidative stress or a nutritional deficit of vitamin E. The oxysterols investigated here are not useful markers for diagnosing AD or MCI.

Association of cholesterol oxidation and abnormalities in fatty acid metabolism in cystic fibrosis.

BACKGROUND: Disarrangement in fatty acids and oxidative stress are features of cystic fibrosis. Cholesterol is very sensitive to oxidative stress. OBJECTIVES: The objectives were to examine whether cholesterol oxidation products are altered in cystic fibrosis and whether they are associated with fatty acids and with characteristics of the disease state. DESIGN: 7-Ketocholesterol and 7beta-hydroxycholesterol (prototype molecules of free radical-mediated cholesterol oxidation) and the fatty acid profile were assessed by mass spectrometry in patients and in sex- and age-matched control subjects. RESULTS: In a comparison with control subjects, mean (+/-SD) cholesterol oxidation was higher (7-ketocholesterol: 11.31 +/- 5.1 compared with 8.33 +/- 5.5 ng/mL, P = 0.03; 7beta-hydroxycholesterol: 14.5 +/- 6.8 compared with 9.7 +/- 4.1 ng/mL, P = 0.004), total saturated fatty acids were higher (31.90 +/- 1.93% compared with 30.31 +/- 0.98%, P < 0.001), monounsaturated fatty acids were higher (29.14 +/- 3.85% compared with 25.88 +/- 2.94%, P = 0.004), omega-6 (n-6) polyunsaturated fatty acids were lower (34.84 +/- 4.77 compared with 39.68 +/- 2.98%, P < 0.0001), and omega-3 (n-3) polyunsaturated fatty acids were comparable in patients with cystic fibrosis. Oxysterols were inversely associated with 24:0 and 18:2 omega-6 fatty acids but did not correlate with the increased oleic acid or with any of the omega-3 fatty acids. CONCLUSIONS: Cystic fibrosis is characterized by relevant cholesterol oxidation that is associated with an abnormal fatty acid profile. The interplay between oxysterols and fatty acids potentially provides insight into the biological mechanisms that underlie this complex disease.