ascorbic-acid and cholesteryl-ester-hydroperoxide

4,6-Di-tert-butyl-2,3-dihydro-2,2-dipentyl-5-benzofuranol (BO-653) is a novel antioxidant synthesized by theoretical findings and considerations. Here we report on the aqueous peroxyl radical-induced oxidation of human plasma in the presence of BO-653. When BO-653 was given to healthy human subjects at 400 mg twice daily for 28 days, lipids in the resulting plasma were protected from oxidation compared with lipids present in plasma from subjects receiving placebo. Similarly, BO-653 added in vitro at 50 muM inhibited the peroxyl radical-induced accumulation of cholesteryl ester hydroperoxides that occurred in the presence of alpha-tocopherol, although BO-653 did not decrease the rate of consumption of ascorbate, albumin-bound bilirubin, and uric acid. The antioxidant action of in vivo and in vitro added BO-653 was associated with the formation of two major reaction products of BO-653, the structures of which were elucidated by mass spectrometry and nuclear magnetic resonance analyses. The products were identified as stereoisomers of dioxybis(4,6-di-tert.-butyl-2,3,5,7a-tetrahydro-2,2-dipentylbenzofuran-5-one). These dialkylperoxides of BO-653 might be useful markers to assess the antioxidant function of BO-653 in biological systems in vivo.

Topics: Albumins; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Benzofurans; Bilirubin; Cholesterol Esters; Humans; Lipid Metabolism; Lipid Peroxidation; Oxidation-Reduction; Peroxides; Plasma; Stereoisomerism; Uric Acid

The mechanism for the formation of active oxygen species and their reactions with antioxidants is described. The importance of the free radical chain oxidation and the singlet oxygen-dependent oxidation is suggested by a decrease in skin levels of alpha-tocopherol, ubiquinol-10, and ascorbic acid with a concomitant formation of lipid hydroperoxides during UV irradiation of murine skin, and the formation of squalene hydroperoxides in human skin upon UV exposure, respectively.

Topics: Animals; Antioxidants; Ascorbic Acid; Cholesterol Esters; Free Radicals; Phosphatidylcholines; Rats; Reactive Oxygen Species; Skin; Skin Aging; Ubiquinone; Ultraviolet Rays; Vitamin E

Lipoxygenase-dependent low-density lipoprotein (LDL) oxidation is believed to be involved in atherogenesis. Inhibition of lipoxygenase-induced lipid peroxidation might, therefore, be an important mode to suppress the development of atherosclerosis. Because dietary antioxidants inhibit LDL oxidation in vitro and their intake is inversely associated with coronary heart diseases, we compared the inhibitory effect of three typical flavonoids-quercetin, epicatechin, and flavone-with alpha-tocopherol and ascorbic acid against human LDL oxidation catalyzed by mammalian 15-lipoxygenase. The oxidative modification of LDL was monitored by measurement of cholesteryl ester hydroperoxide (CE-OOH) formation and consumption of antioxidants by using HLPC. Quercetin and epicatechin were the strongest inhibitors of LDL oxidation catalyzed by 15-lipoxygenase; ascorbic acid was an effective inhibitor in the first 3 h of oxidation; and fivefold alpha-tocopherol-enriched LDL showed a partial inhibition of CE-OOH formation only after 4-6 h of incubation. Flavone had no effect. Quercetin, ascorbic acid, and alpha-tocopherol were consumed in the first 3 h of incubation. Consumption of LDL alpha-tocopherol was partially inhibited by ascorbic acid and quercetin, whereas epicatechin and flavone were without effect. These results emphasize the inhibitory effect of the flavonoids quercetin and epicatechin on 15-lipoxygenase-mediated LDL lipid peroxidation. At similar concentrations, they are stronger antioxidants than ascorbic acid, alpha-tocopherol, and flavone.

Topics: Animals; Antioxidants; Arachidonate 15-Lipoxygenase; Ascorbic Acid; Catechin; Cholesterol Esters; Chromatography, High Pressure Liquid; Flavones; Flavonoids; Humans; Lipid Peroxidation; Lipoproteins, LDL; Micelles; Octoxynol; Quercetin; Time Factors; Vitamin E; Water

Two diet-derived phenolic acids, caffeic and p-coumaric acids, interplayed with ascorbate in the protection of low density lipoproteins (LDL) from oxidation promoted by ferrylmyoglobin. Ferrylmyoglobin, a two-electron oxidation product from the reaction of metmyoglobin and H2O2, was able to oxidize LDL, degrading free cholesterol and cholesteryl esters. Upon exposure to ferrylmyoglobin, LDL became rapidly depleted of cholesteryl arachidonate and linoleate, which turn into the corresponding hydroperoxides. Cholesteryl oleate and cholesterol were, comparatively, more resistant to oxidation. Caffeic (2 microM) and p-coumaric (12 microM) acids efficiently delayed oxidations, as reflected by an increase in the lag times required for linoleate hydroperoxide and 7-ketocholesterol formation as well as for cholesteryl linoleate consumption. At the same concentration, ascorbate, a standard water-soluble antioxidant, was less efficient than the phenolic acids. Additionally, phenolic acids afforded a protection to LDL that, conversely to ascorbate, extends along the time, as inferred from the high levels of cholesteryl linoleate and cholesteryl arachidonate left after 22 hr of oxidation challenging. Significantly, the coincubation of LDL with ascorbate and each of the phenolic acids resulted in a synergistic protection from oxidation. This was inferred from the lag phases of cholesteryl linoleate hydroperoxide (the major peroxide found in LDL) formation in the presence of mixtures of ascorbate with phenolic acids longer than the sum of individual lag phases of ascorbate and the phenolic acids. A similar description could be drawn for the accumulation of a late product of oxidation, 7-ketocholesterol. It is concluded that ferrylmyoglobin induces a typical pattern of LDL lipid peroxidation, the oxidation rate of cholesteryl esters being a function of unsaturation; furthermore, there is a synergistic antioxidant activity of diet-derived phenolic acids with ascorbate in the protection of LDL from oxidation, a finding of putative physiological relevance.

Topics: Animals; Ascorbic Acid; Caffeic Acids; Catalysis; Cholesterol; Cholesterol Esters; Coumaric Acids; Drug Synergism; Horses; Hydrolysis; Hydroxybenzoates; Lipoproteins, LDL; Metmyoglobin; Propionates

A large body of experimental research indicates that the generation of free radicals leading to oxidative stress plays a role in the pathogenesis of ischemic brain injury, but evidence in humans is limited. We examined plasma levels of lipid hydroperoxides (measured as cholesteryl ester hydroperoxides, CEOOH) and ascorbic acid in 32 patients with cortical stroke, as compared with 13 patients with lacunar infarct. Patients with cortical stroke had significantly increased levels of CEOOH, which peaked on Day 5 after the ictus. Small decreases in ascorbic acid concentrations were not significant. There was a significant positive correlation of CEOOH with the NIH stroke scale, and a significant negative correlation with the Glasgow coma scale. Concentrations of CEOOH were significantly higher in patients with total anterior cerebral syndrome as compared with patients with partial anterior cerebral syndrome or posterior cerebral syndrome. Stroke volumes computed from CT or MRI scans were significantly correlated with plasma CEOOH levels. These findings implicate oxidative stress in ischemic brain injury in humans and suggest that measurements of CEOOH in plasma may be useful both prognostically as well as in monitoring therapeutic interventions.

Topics: Aged; Ascorbic Acid; Brain Ischemia; Cerebrovascular Disorders; Cholesterol Esters; Female; Humans; Lipid Peroxides; Magnetic Resonance Imaging; Male; Tomography, X-Ray Computed

Vitamin C (ascorbic acid, AA) can act as an antioxidant or a pro-oxidant in vitro, depending on the absence or the presence, respectively, of redox-active metal ions. Some adults with iron-overload and some premature infants have potentially redox-active, bleomycin-detectable iron (BDI) in their plasma. Thus, it has been hypothesized that the combination of AA and BDI causes oxidative damage in vivo. We found that plasma of preterm infants contains high levels of AA and F2-isoprostanes, stable lipid peroxidation end products. However, F2-isoprostane levels were not different between those infants with BDI (138 +/- 51 pg/ml, n = 19) and those without (126 +/- 41 pg/ml, n = 10), and the same was true for protein carbonyls, a marker of protein oxidation (0.77 +/- 0.31 and 0.68 +/- 0.13 nmol/mg protein, respectively). Incubation of BDI-containing plasma from preterm infants did not result in detectable lipid hydroperoxide formation (10% of its initial concentration. Finally, when iron was added to plasma devoid of AA, lipid hydroperoxides were formed immediately, whereas endogenous and exogenous AA delayed the onset of iron-induced lipid peroxidation in a dose-dependent manner. These findings demonstrate that in iron-overloaded plasma, AA acts an antioxidant toward lipids. Furthermore, our data do not support the hypothesis that the combination of high plasma concentrations of AA and BDI, or BDI alone, causes oxidative damage to lipids and proteins in vivo.

Topics: Adult; Antioxidants; Ascorbic Acid; Bleomycin; Blood Proteins; Cholesterol Esters; Chromatography, High Pressure Liquid; Humans; Infant; Infant, Newborn; Infant, Premature; Iron; Iron Overload; Lipids; Oxidation-Reduction

The pathophysiology of subarachnoid hemorrhage (SAH) may involve free radical production and lipid peroxidation. We examined plasma levels of cholesteryl ester hydroperoxides (CEOOH) and antioxidants in 25 patients with SAH, and 10 neurologic controls with lacunar stroke. Patients with SAH had significantly increased plasma levels of CEOOH, which peaked on day 5 after the ictus. Concentrations of CEOOH were significantly increased, and ascorbic acid concentrations were significantly decreased in patients who developed vasospasm compared with patients without vasospasm. Increased levels of CEOOH were associated with increased mortality and correlated with clinical outcome scales. These results implicate oxidative stress in the pathogenesis of SAH and suggest that measurements of CEOOH in plasma may be useful both prognostically as well as in monitoring therapeutic interventions.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Biomarkers; Cholesterol Esters; Female; Humans; Lipid Peroxides; Male; Middle Aged; Oxidation-Reduction; Severity of Illness Index; Subarachnoid Hemorrhage; Ubiquinone; Uric Acid; Vitamin E

Topics: Allantoin; Antioxidants; Ascorbic Acid; Cholesterol Esters; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Humans; Indicators and Reagents; Nutrition Assessment; Nutritional Status; Phosphatidylcholines; Sensitivity and Specificity; Ultrafiltration; Uric Acid; Vitamin E