0000000000249481
AUTHOR
Daniele D'arpa
Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in β-thalassemia intermedia patients
Fifteen beta-thalassemia intermedia patients, not requiring chronic transfusional therapy, were monitored in order to check their antioxidant status, and the lipid oxidation products in plasma, LDL, and erythrocytes before and during a 9-month oral treatment with 600 mg/day vitamin E. The low level of vitamin E, and high level of malondialdehyde in plasma clearly tended to normalize after three months (P < .001), and were quite similar to control after six months. The abnormally low level of vitamin E in LDL and the four times higher than control basal level of conjugated dienes (LDL-CD), were not modified after three months of treatment. Significant changes of LDL-VE (P < .05) and of the b…
Oxidative stress after moderate to extensive burning in humans.
Lipid peroxidation products, lipid antioxidants, and hematologic and blood chemistry changes were evaluated in plasma of patients after acute burning injury involving 10% (n=8), 20% (n=8), and 40% (n=5) of total body surface area (TBSA), 24 h after burning (baseline) up to 30 days after. Markedly increased plasma levels of malondialdehyde (MDA) were observed at baseline in all patients, according to the extent of the injury, then the values declined progressively. However, levels of MDA remained above normal up to 30 days even in less injured patients. On the other hand, the plasma level of conjugated diene lipid hydroperoxides was only slightly higher than control at the baseline, then dro…
Melatonin protects human red blood cells from oxidative hemolysis: new insights into the radical-scavenging activity.
Antioxidant activity of melatonin in human erythrocytes, exposed to oxidative stress by cumene hydroperoxide (cumOOH), was investigated. CumOOH at 300 microM progressively oxidized a 1% suspension of red blood cells (RBCs), leading to 100% hemolysis in 180 min. Malondialdehyde and protein carbonyls in the membrane showed a progressive increase, as a result of the oxidative damage to membrane lipids and proteins, reaching peak values after 30 and 40 min, respectively. The membrane antioxidant vitamin E and the cytosolic reduced glutathione (GSH) were totally depleted in 20 min. As a consequence of the irreversible oxidative damage to hemoglobin (Hb), hemin accumulated into the RBC membrane d…
Exposure to malondialdehyde induces an early redox unbalance preceding membrane toxicity in human erythrocytes.
This work investigated the oxidative injury to human red blood cells (RBCs) by the exposure to exogenous malondialdehyde (MDA), in a physiological environment. When a 10% RBC suspension was incubated in autologous plasma, in the presence of 50 microM MDA, 30% of MDA entered into the cells. A time-course study showed that MDA caused early (30-120 min) and delayed (3-18 h) effects. MDA caused a fast depletion of reduced glutathione, and loss of the glucose-6-phosphate dehydrogenase activity, followed by a decrease of HbO2. Accumulation of methemoglobin, and formation of small amounts of hemichrome were later evident. Also, an HbO2-derived fluorescent product was measured in the membrane. The …
Oxidative Modification of Low-Density Lipoprotein and Atherogenetic Risk in β-Thalassemia
AbstractWe investigated the oxidative state of low-density lipoprotein (LDL) in patients with β-thalassemia to determine whether there was an association with atherogenesis. Conjugated diene lipid hydroperoxides (CD) and the level of major lipid antioxidants in LDL, as well as modified LDL protein, were evaluated in 35 β-thalassemia intermedia patients, aged 10 to 60, and compared with age-matched healthy controls. Vitamin E and β-carotene levels in LDL from patients were 45% and 24% of that observed in healthy controls, respectively. In contrast, the mean amount of LDL-CD was threefold higher and lysil residues of apo B-100 were decreased by 17%. LDL-CD in thalassemia patients showed a str…
Oxidation resistance of LDL is correlated with vitamin E status in beta-thalassemia intermedia.
The alteration of the oxidant/antioxidant balance may affect the susceptibility of low density lipoproteins (LDL) to oxidation in haemolytic disorders such as thalassemia. Thirty patients affected by beta-thalassemia intermedia were examined, and compared with age-matched healthy controls. The mean amount of vitamin E in the thalassemic LDL was lower than control (p0.0001), either when it was calculated on the base of LDL protein (61% decrease) or cholesterol (25% decrease). The LDL resistance to Cu2+-induced oxidation, evaluated as the length of the lag phase before the onset of conjugated diene (CD) lipid hydroperoxide production, was 20% lower than control. Other parameters of LDL suscep…
Increased resistance to oxidation of betalain-enriched human low density lipoproteins
Betalains are natural pigments recently considered as compounds with potential antioxidative properties. In this work, ex vivo plasma spiking of pure either betanin or indicaxanthin, followed by isolation of low density lipoprotein (LDL), and measurement of its resistance to copper-induced oxidation, has been used to research if these betalains can bind to LDL and prevent oxidation of LDL lipids. When pooled human plasma from 10 healthy volunteers was incubated in the presence of 25-100 microM either betanin or indicaxanthin, incorporation of both compounds in LDL was observed, with a maximum binding of 0.52 +/- 0.08, and 0.51 +/- 0.06 nmoles of indicaxanthin and betanin, respectively, per …
Oxidative stress and antioxidant status in beta-thalassemia major: iron overload and depletion of lipid-soluble antioxidants
Because of continuous blood transfusions, thalassemia patients are subjected to peroxidative tissue injury by the secondary iron overload. In accordance, analysis of serum from 42 beta-thalassemia patients, aged 4 to 40 years, showed that the mean concentrations of conjugated diene lipid hydroperoxides (CD), lipoperoxides evaluated as malondialdehyde/ thiobarbituric acid (MDA/TBA) adducts, and protein carbonyls increased about twofold with respect to control. Ferritin levels were positively correlated with the amount of MDA (r = .41; P = .007) and showed a positive trend with CD (r = .31; P = .07) and protein carbonyls (r = .35; P = .054), as further evidence of the deleterious effects of h…
Synergistic Interactions between Vitamin A and Vitamin E against Lipid Peroxidation in Phosphatidylcholine Liposomes
Interactions between alpha-tocopherol and all-trans retinol in suppressing lipid peroxidation were studied in a unilamellar liposomal system of phosphatidylcholine from either egg or soybean, in which peroxidation was initiated by the water-soluble azo initiator 2,2-azobis(2-amidino-propane)hydrochloride and peroxidation was measured as production of conjugated diene hydroperoxides. While all-trans retinol alone was poorly effective, the combination of all-trans retinol with alpha-tocopherol caused an inhibition period far beyond the sum of the inhibition periods observed with individual antioxidants, providing evidence of synergistic interactions. Furthermore, the inhibition rate calculate…
Antioxidant reactions of all-trans retinol in phospholipid bilayers: effect of oxygen partial pressure, radical fluxes, and retinol concentration.
Lipoperoxyl radical-scavenging activity of retinol in unilamellar soybean phosphatidylcholine liposomes was studied under a variety of conditions to appreciate to what extend retinol may be considered an effective antioxidant. Peroxidation, initiated by 2 mM 2,2'-azobis(amidino-propane)hydrochloride (AAPH), was carried out at 160 torr O2 or at 15 torr O2, in the absence or in the presence of 10 to 40 mM retinol. As evaluated by the length of the inhibition periods, t(inh), and by the ratio between the inhibition and propagation rate, R(inh)/R(p), the antioxidant activity of retinol was higher at 15 torr O2 than at 160 torr O2. The consumption rate of retinol was markedly faster at 160 torr …
Reaction of melatonin with hemoglobin-derived oxoferryl radicals and inhibition of the hydroperoxide-induced hemoglobin denaturation in red blood cells
Melatonin has been shown to act as a radical scavenger in various chemical and biological model systems in vitro. Kinetic evidence is now provided showing that melatonin inhibits the irreversible degradation of hemoglobin (Hb), when incubated with red blood cells exposed to the oxidant activity of cumene hydroperoxide (cumOOH). A decrease of heme loss and accumulation of soluble methemoglobin (met-Hb) are explained in terms of the interaction of the indoleamine with perferryl Hb ( . Hb[Fe IV = O]), a highly reactive Hb-derived radical species responsible for the irreversible Hb degradation. A kinetic study, in pure chemical solution, showed that melatonin can effectively reduce the oxoferry…
Oxidation of melatonin by oxoferryl hemoglobin: A mechanistic study
Reaction of melatonin with the hypervalent iron centre of oxoferryl hemoglobin, produced in aqueous solution from methemoglobin and H2O2, has been investigated at 37 degrees C and pH 7.4, by absorption spectroscopy. The reaction results in reduction of the oxoferryl moiety with formation of a heme-ferric containing hemoprotein. Stopped-flow spectrophotometric measurements provide evidence that the reduction of oxoferryl-Hb by melatonin is first-order in oxoferryl-Hb and first-order in melatonin. The bimolecular reaction constant at pH 7.4 and 37 degrees C is 112 +/- 1.0 M(-1) s(-1). Two major oxidation products from melatonin have been found by gas chromatography-mass spectroscopy: the cycl…
Reaction of melatonin with lipoperoxyl radicals in phospholipid bilayers.
Melatonin, at 5 to 500 microM was incorporated in unilamellar soybean phosphatidylcholine (PC) liposomes, the peroxidation of which was induced by 2,2'-azobis (2-amidinopropane-hydrochloride) (AAPH), and measured as production of conjugated diene lipid hydroperoxides. Concentration as low as 5 and 10 microM were poorly effective in reducing lipid peroxidation. Melatonin at 30 to 500 microM caused short inhibition periods, increasing with, but not linearly related to concentration, with a concurrent net decrease of the propagation rate. The time course of melatonin oxidation, measured as loss of fluorescence, was studied during the AAPH-stimulated peroxidation of soybean PC liposomes, or whe…