Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant (original) (raw)
Related papers
Current controlled trials in cardiovascular medicine, 2002
BACKGROUND: Antioxidant supplementation with vitamin E had no effect in the prevention of cardiovascular diseases (CVD) in three recent large, randomized clinical trials. In order to reassess critically the role of vitamin E in CVD prevention, it is important to establish whether these results are related to a lack of antioxidant action. METHODS: We examined the in vivo antioxidant effect of vitamin E (300 mg/day for about three years) in 144 participants in the Primary Prevention Project (females and males, aged >/= 50 y, with at least one major CV risk factor, but no history of CVD). Urinary 8-epi-PGF2alpha (isoprostane F2alpha-III or 15-F2t-isoP), a validated biomarker of lipid peroxidation, was measured by mass spectrometry. RESULTS: Urinary excretion of 8-epi-PGF2alpha [pg/mg creatinine, median (range)] was 141 (67-498) in treated and 148 (76-561) in untreated subjects (p = 0.10). Taking into account possible confounding variables, multiple regression analysis confirmed that...
Proceedings of the National Academy of Sciences, 1995
The aim of our study was to investigate the relationships between the levels of coenzyme Q10 (CoQ10) and vitamin E and the levels of hydroperoxide in three subfractions of low density lipoproteins (LDL) that were isolated from healthy donors. LDL3, the densest of the three subfractions, has shown statistically significant lower levels of CoQ10 and vitamin E, which were associated with higher hydroperoxide levels when compared with the lighter counterparts. After CoQ10 supplementation, all three LDL subfractions had significantly increased CoQ10 levels. In particular, LDL3 showed the highest CoQ10 increase when compared with LDL1 and LDL2 and was associated with a significant decrease in hydroperoxide level. These results support the hypothesis that the CoQ10 endowment in subfractions of LDL affects their oxidizability, and they have important implications for the treatment of disease.
Lipids, 1989
The role of vitamin E in the protection against iron dependent lipid peroxidation was studied in rat liver microsomes and Triton‐dispersed microsomal lipid micelles. In these systems, an antioxidant effect of vitamin E at a physiological ratio to phospholipids could be observed only in the presence of phospholipid hydroperoxide glutathione peroxidase (PHGPX) and glutathione. The rationale of this cooperation is discussed on the basis of the hydroperoxyl radical scavenging capacity of vitamin E and the reduction of membrane hydroperoxides by PHGPX. The scavenging of lipid hydroperoxyl radicals by vitamin E, although inhibiting propagation of the peroxidative chain, produces lipid hydroperoxides from which ferrous iron generates alkoxyl radicals that react with vitamin E almost as fast as with fatty acids. Therefore, only if membrane hydroperoxides are continuously reduced by this specific peroxidase does the scavenging of hydroperoxyl radicals by vitamin E lead to an effective inhibi...
Iranian biomedical journal, 2013
Oxidative modification of low-density lipoprotein (LDL) appears to be an early step in the pathogenesis of atherosclerosis. Meanwhile, myeloperoxidase (MPO)-catalyzed reaction is one of the potent pathway for LDL oxidation in vivo. The aim of this study was to evaluate in vitro antioxidant effects of vitamins C and E on LDL oxidation mediated by MPO. MPO was isolated from fresh plasma by sequential centrifugation using density ultracentrifugation. It was incubated with LDL and the LDL oxidation level was determined spectrophotometrically by measuring conjugated diene absorbance at 234 nm. Furthermore, vitamin C (50-200 mM) and vitamin E (10-40 mM) were added and the LDL oxidation level was determined. The purity index of MPO and its enzymatic activity were 0.69 and 1127 U/mg protein, respectively. It was demonstrated that vitamin C in vitro inhibited LDL oxidation mediated by MPO; however, vitamin E was unable to act in the same way. The protection by vitamin C was concentration dep...
The Journal of Nutritional Biochemistry, 2002
Expression of antioxidant enzymes (AOE), an important mechanism in the protection against oxidative stress, could be modified by the redox status of the cells. The aim of this project was to evaluate the role of vitamin E deficiency in association with a high-cholesterol diet in the hepatic lipid peroxidation and the expression of AOE. Two groups of 6 male rats were fed with a high-cholesterol or a high-cholesterol vitamin E-deficient diet. All animals were sacrificed at 72 days of treatment. Liver lipid peroxidation index (Malondialdehyde ; MDA) and hepatic AOE were evaluated. Total liver RNA was extracted, and the steady state messenger RNA (mRNA) levels of glutathion peroxydase, manganese superoxide dismutase, Cu/Zn superoxide dismutase and catalase were examined by northern blot. After 72 days on the diet, a significant increase in the lipid peroxidation index was observed in the vitamin E deficient group (MDA : 4.45 Ϯ 0.29 nmol/mg protein versus 3.65 Ϯ 0.1 nmol/mg protein in vitamin E normal group). Despite this oxidative stress, the activities and mRNA levels of liver AOE were not significantly different in the 2 groups. These preliminary results show that chronic vitamin E deficiency associated with high cholesterol diet is able to increase lipid peroxidation without modulation of AOE expression and activity in the liver. This suggests that beneficial effects of dietary vitamin E are due to a plasma antioxidant effect or a cell mediated action, rather than to a specific modulation of cellular enzymes.
Arteriosclerosis, Thrombosis, and Vascular Biology, 1993
In previously reported in vitro studies, we found that heme, a physiologically widespread hydrophobic iron compound, can rapidly generate oxidized low-density lipoprotein (LDL), which then becomes cytotoxic to cultured vascular endothelial cells; both LDL oxidation and endothelial cytotoxicity were inhibited by incubation with exogenous a-tocopherol (vitamin E) or ascorbic acid (vitamin C). Seeking relevance to in vivo conditions, we performed a study in which 10 human volunteers were given daily antioxidant supplements of 800 IU of DL-<x-tocopherol acetate alone or in combination with 1000 mg of ascorbic acid for 2 weeks. LDL resistance to heme oxidation ex vivo, as measured by the lag time for conjugated-diene formation, increased by as much as threefold from a mean±SD of 58±11 to 104±18 minutes (P<.001); LDL a-tocopherol increased from 11 ±2 to 26±6 molecules per LDL particle (P<.001); and most impressively, cytotoxicity to porcine aortic endothelial cells incubated with LDL conditioned with heme plus H 2 O 2 or with copper was completely prevented (cytotoxicity before supplementation was 42 + 12%, decreasing after supplementation to 3±2%, P<.001). These measurements reverted to their presupplement levels within 2 weeks after participants stopped taking antioxidant supplements and were reproduced in 4 subjects taking 800 IU of DL-a-tocopherol acetate supplements alone but not in the same subjects taking 1000 mg ascorbic acid supplements alone. In conclusion, oral vitamin E supplementation increases LDL or-tocopherol content, increases LDL resistance to oxidation, and decreases the cytotoxicity of oxidized LDL to cultured vascular endothelial cells. (Arterioscler Thromb. 1993;13:1779-1789.) KEY WORDS iron • vitamin E • LDL • oxidized LDL • vitamin C • atherosclerosis • heme •
Lipid peroxidation in relation to vitamin C and vitamin E levels
Central European journal of public health, 2004
Oxidative stress plays an important contributory role in the pathogenesis of age-related chronic diseases. Increased lipid peroxidation process is caused by an enhanced free radical formation together with a higher supply of substrates and by an insufficient defense by antioxidants as well. Levels of malondialdehyde to content of lipid peroxidation substrates (polyunsaturated fatty acids), promoters (homocysteine--hydroxyl radical producer) and inhibitors (essential vitamins C and E) were estimated in a group (n=92) of subjective healthy adults randomly selected from general population. The relationship of malondialdehyde levels to values of peroxidisability index of fatty acids as well as to levels of homocysteine is significantly positive linear A significant inverse linear correlation between malondialdehyde levels and natural antioxidant levels (vitamin C, vitamin E) was recorded. Lipid peroxidation products (conjugated dienes of fatty acids--initial, malondialdehyde--secondary)...
Archives of Biochemistry and Biophysics, 1997
dant reactions and antioxidant effects in an intact organ system during oxidative stress. ᭧ 1997 Academic Press We have investigated the relationship between vitamin E (a-tocopherol, TH) oxidation and antioxidant protection in a perfused rat liver model. Perfusion of a male Sprague-Dawley rat liver with 2 mM tert-butyl-The lipid-soluble chain-breaking antioxidant TH 3 hydroperoxide (t-BuOOH) for 10 min resulted in lipid (Fig. 1) protects cell membranes and lipoproteins peroxidation and metabolic changes reflecting oxidaagainst oxidative damage [reviewed in (1)]. The fate of tive stress. Mitochondria isolated from the liver exhib-TH in radical scavenging reactions has been identified ited increases in state 3 and state 4 respiration and a previously in chemical model systems (2-6) and most decline in the respiratory control ratio. In livers from rats given supplementary vitamin E in the diet, TH recently in mitochondria in vitro (7). TH scavenges percontent was 7-to 10-fold higher than in controls and oxyl radicals by a two-reaction sequence. Initial hydrolipid peroxidation and metabolic changes induced by gen transfer from TH to a peroxyl radical (Eq. [1]) is t-BuOOH were decreased. In mitochondria from these followed by reaction of the resulting tocopheroxyl radivitamin E-supplemented livers, the t-BuOOH-induced cal with another peroxyl radical to yield a nonradical increase in state 4 respiration was reduced and the product (Eq. [2]). respiratory control ratio was maintained. In livers from unsupplemented rats, t-BuOOH induced oxida-TH / ROOr r Tr / ROOH [1] tion of TH to a-tocopherolquinone, a-tocopherolhydroquinone, 2,3-epoxy-a-tocopherolquinone, and 5,6-157