Autoxidation in micelles. Synergism of vitamin C with lipid-soluble vitamin E and water-soluble Trolox

Barclay, L. R. C.; Locke, Steven J.; MacNeil, Joseph Mark

doi:10.1139/v85-062

Cited by 109 publications

(53 citation statements)

References 19 publications

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“…α-Tocopherol is, indeed, positioned at the LDL-water interface [35,36] and is therefore promptly accessible to react with the water-soluble uric acid. This kind of synergism has also been proposed for ascorbic acid and for the water-soluble analogue of α-tocopherol, Trolox C [37]. The pro-oxidant activity of Cu(I) is much more established and characterized and basically relies on its interaction with lipid hydroperoxides, as described in eqn.…”

Section: Discussionmentioning

confidence: 87%

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

Bagnati

Perugini

Cau

et al. 1999

Biochemical Journal

135

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The inclusion of uric acid in the incubation medium during copper-induced low-density lipoprotein (LDL) oxidation exerted either an antioxidant or pro-oxidant effect. The pro-oxidant effect, as mirrored by an enhanced formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances and increase in negative charge, occurred when uric acid was added late during the inhibitory or lag phase and during the subsequent extensive propagation phase of copper-stimulated LDL oxidation. The pro-oxidant effect of uric acid was specific for copper-induced LDL oxidation and required the presence of copper as either Cu(I) or Cu(II). In addition, it became much more evident when the copper to LDL molar ratio was below a threshold value of approx. 50. In native LDL, the shift between the antioxidant and the pro-oxidant activities was related to the availability of lipid hydroperoxides formed during the early phases of copper-promoted LDL oxidation. The artificial enrichment of isolated LDL with α-tocopherol delayed the onset of the pro-oxidant activity of uric acid and also decreased the rate of stimulated lipid peroxidation. However, previous depletion of α-tocopherol was not a prerequisite for unmasking the pro-oxidant activity of uric acid, since this became apparent even when α-tocopherol was still present in significant amounts (more than 50% of the original values) in LDL. These results suggest, irrespective of the levels of endogenous α-tocopherol, that uric acid may enhance LDL oxidation by reducing Cu(II) to Cu(I), thus making more Cu(I) available for subsequent radical decomposition of lipid peroxides and propagation reactions.

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Section: Discussionmentioning

confidence: 87%

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

Bagnati

Perugini

Cau

et al. 1999

Biochemical Journal

135

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“…IIIE). For example, ascorbate efficiently scavenges aqueous peroxyl (33,34) and protein radicals (202,1052,1060) Present in very low concentrations only. However, it appears to represent the first line of lipid-soluble antioxidant defense in human lipoproteins (666).…”

Section: I) Ascorbate (Vitamin C)mentioning

confidence: 99%

Role of Oxidative Modifications in Atherosclerosis

Stocker¹,

Keaney²

2004

Physiological Reviews

2,257

1,756

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This review focuses on the role of oxidative processes in atherosclerosis and its resultant cardiovascular events. There is now a consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. The oxidative modification hypothesis of atherosclerosis predicts that low-density lipoprotein (LDL) oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis. In support of this hypothesis, oxidized LDL can support foam cell formation in vitro, the lipid in human lesions is substantially oxidized, there is evidence for the presence of oxidized LDL in vivo, oxidized LDL has a number of potentially proatherogenic activities, and several structurally unrelated antioxidants inhibit atherosclerosis in animals. An emerging consensus also underscores the importance in vascular disease of oxidative events in addition to LDL oxidation. These include the production of reactive oxygen and nitrogen species by vascular cells, as well as oxidative modifications contributing to important clinical manifestations of coronary artery disease such as endothelial dysfunction and plaque disruption. Despite these abundant data however, fundamental problems remain with implicating oxidative modification as a (requisite) pathophysiologically important cause for atherosclerosis. These include the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis, and observations in animals that suggest dissociation between atherosclerosis and lipoprotein oxidation. Indeed, it remains to be established that oxidative events are a cause rather than an injurious response to atherogenesis. In this context, inflammation needs to be considered as a primary process of atherosclerosis, and oxidative stress as a secondary event. To address this issue, we have proposed an “oxidative response to inflammation” model as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.

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“…AH can reduce a variety of oxidizing species, including alkoxyl and peroxyl radicals, to eliminate harmful free-radical reactions in aqueous compartments within and outside cells [2]. AH also efficiently maintains α-tocopherol (vitamin E) in itro by reducing α-tocopheroxyl radicals [3]. Thus AH effectively protects plasma lipids against peroxidation by reducing both aqueous [4] and lipid-associated radicals [5].…”

Section: Introductionmentioning

confidence: 99%

Efflux of hepatic ascorbate: a potential contributor to the maintenance of plasma vitamin C

Upston

Karjalainen

Bygrave

et al. 1999

Biochemical Journal

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Ascorbate (AH, the reduced form of vitamin C) is an important radical scavenger and antioxidant in human plasma; the resulting ascorbyl radical can disproportionate to AH and dehydroascorbic acid (DHA). Here we address potential maintenance mechanism(s) for extracellular AH by examining the ability of cells to convert extracellularly presented DHA to AH. DHA was rapidly transported into human liver (HepG2), endothelial and whole blood cells invitro by plasma membrane glucose transporters and reduced intracellularly. Liver cells displayed the highest capacity to release the intracellularly accumulated AH. The proteins responsible for DHA uptake and AH release could be distinguished by inhibitor studies. Thus, unlike DHA uptake, AH efflux was largely insensitive to cytochalasin B and thiol-reactive agents but was inhibited by phloretin, 4,4′-di-isothiocyanostilbene-2,2′-disulphonate and isoascorbate. Efflux of AH from cells was temperature-sensitive and saturable with a low affinity (millimolar, intracellular) for AH. In addition to isolated liver cells, perfusion of intact rat and guinea-pig liver with DHA resulted in AH in the circulating perfusate. Our results show that hepatocytes take up and reduce DHA and subsequently release part of the AH formed, probably via a membrane transporter. By converting extracellular DHA to extracellular AH, the liver might contribute to the maintenance of plasma AH, a process that could be important under conditions of oxidative stress.

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Autoxidation in micelles. Synergism of vitamin C with lipid-soluble vitamin E and water-soluble Trolox

Cited by 109 publications

References 19 publications

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

When and why a water-soluble antioxidant becomes pro-oxidant during copper-induced low-density lipoprotein oxidation: a study using uric acid

Role of Oxidative Modifications in Atherosclerosis

Efflux of hepatic ascorbate: a potential contributor to the maintenance of plasma vitamin C

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