Interaction of carotenoids and tocopherols with peroxynitrite.
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Animals↗
Biomedical subjects
C Rice-Evans
Publications and source records attributed to C Rice-Evans.
Antioxidant activity applying an improved ABTS radical cation decolorization assay.
A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.
Antioxidants↗
Do iron and vitamin C co-supplementation influence platelet function or LDL oxidizability in healthy volunteers?
OBJECTIVE: To examine the effect of co-supplementation with iron and vitamin C on antioxidant status, platelet function and low density lipoprotein oxidation in normal healthy volunteers. DESIGN: The study was carried out with two groups of 20 subjects each acting as their own control, comparing presupplemention with postsupplemention. One group was supplemented with iron and the RDA level of vitamin C and the second group with iron and 260 mg/d vitamin C. SETTING: The International Antioxidant Research Centre, The Guy's, King's College and St Thomas's School of Biomedical Science, Guy's Campus, London. SUBJECTS: Forty normal healthy volunteers, recruited from the staff of the Medical School and Hospital in which two volunteers withdrew during the study. INTERVENTIONS: Subjects in both studies were randomly assigned to one of two groups (5 males and 5 females group) and received supplements containing iron (14 mg/d) and either 60 mg/d (Group A) or 260 mg/d (Group B) vitamin C for 12 wk. Blood samples were taken at 6 wk and 12 wk, and prior to supplementation and analysed for iron and antioxidant status (transferrin bound iron, vitamin C and E, and beta-carotene levels) in both studies. Samples from the first study were analysed for the susceptibility of LDL isolated from plasma to Cu2+-induced oxidation and samples from the second for platelet function. RESULTS: Transferrin-bound iron was significantly increased (P < 0.05) at 12 wk, in Group A subjects (from 14.9+/-5.3 micromol/1 to 19.5+/-2.3 micromol/l; mean+/-s.d.; n=19), whereas those in Group B showed a significant increase (P < 0.05) after 6 wk (from 15.8+/-4.5 micromol/l to 20.4+/-6.6 micromol/l; n = 19) which decreased at 12 wk (16.3+/-5.0 micromol/l). Plasma total ascorbate significantly increased from an initial level of 59.3+/-21.3 micromol/l to 87.6+/-29.0 micromol/l after 6 wk and 81.7+/-11.4 micromol/l after 12 wk following the Group B supplementation, but only after 12 wk in Group A (from 64.0+/-24.8 micromol/l to 77.2+/-13.2 micromol/l). Plasma alpha-tocopherol concentrations were significantly increased after 6 wk and 12 wk with both levels of supplementation (from 24.2+/-5.71 micromol/l Group A and 23.4+/-5.3 micromol/l Group B to 26.3+/-5.5 micromol/l and 25.71+/-4.7 micromol/1 respectively at 12wk). The mean lag phase to oxidation of low density lipoprotein (LDL) was significantly increased in subjects in Group B after 12 wk ingestion of iron and 260 mg vitamin C (from 80.0+/-14.8 min to 97.2+/-16.9 min; n = 9). Platelet sensitivity to ADP-induced aggregation was significantly decreased (P < 0.05) by 12 wk in Group A (from EC50 2.3 < or = 1.3 microM to 3.7+/-2.2 microM; n = 10), whereas those receiving higher vitamin C showed a significant decrease (P < 0.05; from EC50 1.9+/-0.6 microM to 3.1+/-1.8 microM) after 6wk which subsequently increased towards presupplemental levels (2.6+/-1.6 microM). Platelets from the latter subjects showed a significant reduction in ADP-induced ATP secretion at both 6wk and 12 wk. CONCLUSION: The results show modest beneficial effects on LDL oxidation and platelet function following supplementation with iron and vitamin C. No evidence for pro-oxidant effects was observed.
Adenosine Diphosphate↗
Inhibition of peroxynitrite-mediated oxidation of dopamine by flavonoid and phenolic antioxidants and their structural relationships.
The interaction between peroxynitrite and dopamine and the inhibition of this reaction by plant-derived antioxidants have been investigated. Peroxynitrite promoted the oxidation of dopamine to 6-hydroxyindole-5-one as characterised by HPLC and photodiode array spectra, akin to the products of the tyrosinase-dopamine reaction, but no evidence of dopamine nitration was obtained. Although peroxynitrite did not cause nitration of dopamine in vitro, the catecholamine is capable of inhibiting the formation of 3-nitrotyrosine from peroxynitrite-mediated nitration of tyrosine. The plant-derived phenolic compounds, caffeic acid and catechin, inhibited peroxynitrite-mediated oxidation of dopamine. This effect is attributed to the ability of catechol-containing antioxidants to reduce peroxynitrite through electron donation, resulting in their oxidation to the corresponding o-quinones. The antioxidant effect of caffeic acid and catechin was comparable to that of the endogenous antioxidant, glutathione. In contrast, the structurally related monohydroxylated hydroxycinnamates, p-coumaric acid and ferulic acid, which inhibit tyrosine nitration through a mechanism of competitive nitration, did not inhibit peroxynitrite-induced dopamine oxidation. The findings of the present study suggest that certain plant-derived phenolics can inhibit dopamine oxidation.
Antioxidants↗
Implications of the mechanisms of action of tea polyphenols as antioxidants in vitro for chemoprevention in humans.
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Antioxidants↗
Bioavailability of ferulic acid.
There is a wealth of evidence for the powerful antioxidant properties in vitro of flavonoid components of the diet. However, few studies have been undertaken concerning the hydroxycinnamates, major constituents of fruit, some vegetables, beverages, and grains, particularly the extent to which they are absorbed in vivo from the diet. The study described here has investigated the bioavailability of ferulic acid in humans, from tomato consumption, through the monitoring of the pharmacokinetics of excretion in relation to intake. The results show that the peak time for maximal urinary excretion is approximately 7 h and the recovery of ferulic acid in the urine, on the basis of total free ferulic acid and feruloyl glucuronide excreted, is 11-25% of that ingested.
Adult↗
Modulation of the UVA activation of haem oxygenase, collagenase and cyclooxygenase gene expression by epigallocatechin in human skin cells.
We have investigated the modifying effects of epigallocatechin, a major polyphenolic constituent of green tea, on ultraviolet-A-activated gene expression in human fibroblasts and keratinocytes using the stress responsive enzymes: haem oxygenase-1, interstitial collagenase and cyclooxygenase-2. Although epigallocatechin strongly reduced ultraviolet-A-induced haem oxygenase-1 activation in skin-derived 'fibroblasts, the same compound activated collagenase and cyclooxygenase expression. In a keratinocyte cell line, ultraviolet-A-mediated haem oxygenase-1 over-expression was low and epigallocatechin failed to modulate it further. In contrast to the results with fibroblasts, ultraviolet-A activation of cyclooxygenase in keratinocytes was reduced by epigallocatechin. The results indicate that the effect of this green tea polyphenol on cellular stress responses is complex and may involve direct effects on signal transduction as well as changes that may be associated with its antioxidant activity.
Catechin↗
Peroxynitrite oxidises catechols to o-quinones.
Nitration of phenolic compounds is a well-established mechanism on interaction with peroxynitrite. However, while nitration is the predominant reaction for monophenolic hydroxycinnamates, this does not take place with the catechol-containing hydroxycinnamate, caffeic acid. The aim of the present study was to investigate the mechanism of the chemical interaction of caffeic acid with peroxynitrite and to characterise the products formed. A novel compound was detected and characterised as the o-quinone of caffeic acid based on its reaction with nucleophilic thiol compounds, glutathione and L-cysteine. The same novel product was identified following the oxidation of caffeic acid in alkaline solutions confirming the identity of this species as a caffeic acid oxidation product.
Caffeic Acids↗
The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers.
The effects of co-supplementing healthy volunteers with iron (14 mg/day ferrous sulphate) and vitamin C (either 60 mg/day or 260 mg/day as ascorbic acid) on levels of oxidative DNA damage in white blood cells were studied. The subjects were divided into two groups: one group of 20 volunteers with a higher mean initial level of plasma vitamin C (71.9 +/- 14.0 mumol/l) and a second group of 18 volunteers with a lower mean level (50.4 +/- 25.8 mumol/l). In the first group there was a significant rise in several oxidative DNA base damage products and in total oxidative DNA damage in DNA extracted from white blood cells, but not in 8-hydroxyguanine, after 6 weeks of supplementation. However, after 12 weeks levels returned approximately to normal. In the group with the lower initial level of plasma ascorbate, presupplemental levels of oxidative DNA damage were higher and decreased on supplementation with iron and ascorbate. Since oxidative DNA damage has been suggested as a risk factor for the development of cancer, the implications of increased levels in well-nourished subjects after iron/ascorbate supplementation are disturbing in view of the frequent use of dietary supplements containing both iron salts and ascorbate.
Adult↗
Interaction of peroxynitrite with carotenoids and tocopherols within low density lipoprotein.
Peroxynitrite is a powerful oxidising and nitrating agent generated in vivo by the combination of nitric oxide and superoxide. Previous studies have shown that on exposure to peroxynitrite, low density lipoprotein (LDL) is modified resulting in both a time- and concentration-dependent change to lipid and protein components. The present investigation highlights the reaction between carotenoids and tocopherols, present within the lipophilic phase of LDL, and peroxynitrite at varying concentrations. It was observed that the carotenoids were consumed by a significantly greater proportion than that of the tocopherols with lycopene (87.2 +/- 11%) being more reactive than beta-carotene (68.2 +/- 5.8%) when exposed to peroxynitrite (50 microM) for 1 min. Among the tocopherols, alpha-tocopherol (54.9 +/- 20.2%) was more extensively depleted than gamma-tocopherol (14.7 +/- 1.09%) at peroxynitrite concentration of 500 microM. It was also observed that peroxynitrite, unlike copper ions, does not lead to significant peroxidation of LDL as determined by the formation of conjugated dienes and thiobarbituric acid-reactive substances.
Carotenoids↗
Inhibition of nitrous acid-dependent tyrosine nitration and DNA base deamination by flavonoids and other phenolic compounds.
Exposure of tyrosine or DNA bases to acidic nitrite at low pH results in the nitration of tyrosine and the formation of base deamination products, respectively. At pH 1, hypoxanthine and xanthine are formed from the deamination of adenine and guanine, respectively, whereas under the same conditions, uracil is not detected. The yield of 3-nitrotyrosine derived from interaction of equimolar nitrite and tyrosine at pH 1 is approximately 50% of that obtained from equimolar peroxynitrite-tyrosine interactions at pH 7. 4. The ability of a range of plant phenolic constituents to prevent damage mediated by acidic nitrite was also examined in comparison with the activity of vitamin C. The epicatechin/gallate family of flavonols, constituents of green tea, red wine, etc., demonstrates the most extensive inhibitory properties against both tyrosine nitration and base deamination. The results also show that ascorbic acid is a poor inhibitor of nitration or deamination under acidic conditions such as those of the stomach. The ability of plant phenolics to scavenge reactive nitrogen species derived from acidic nitrite may contribute to the protective effects of tea polyphenols against gastric cancer.
Chromatography, High Pressure Liquid↗
Functional food science and defence against reactive oxidative species.
This paper assesses critically the science base that underpins the argument that oxidative damage is a significant causative factor in the development of human diseases and that antioxidants are capable of preventing or ameliorating these disease processes. The assessment has been carried out under a number of headings, and some recommendations for future research are made based on the present day knowledge base. The knowledge database (1) Consideration of the basic science that underlies understanding of the role of free radicals in causing cellular pathologies, and the role of antioxidants in preventing this, shows that an imbalance of reactive oxygen species and antioxidant defence systems may lead to chemical modifications of biologically relevant macromolecules. This imbalance provides a logical pathobiochemical mechanism for the initiation and development of several disease states. Experimental data obtained in vivo provide evidence that antioxidants function in systems that scavenge reactive oxygen species and that these are relevant to what occurs in vivo. The relevance in vivo of these observations depends inter alia on knowledge of the uptake and distribution of the antioxidant within the human body, and on what tissue levels of the antioxidant may be expected in relation to dietary levels. (2) There is some way to go until validated precise methods are available for measuring biomarkers of oxidative damage in human subjects in vivo under minimally invasive conditions. With respect to oxidative damage in DNa, HPLC and GC-mass spectrophotometry methods have both merits and limitations. Lipid oxidation products in plasma are best measured as isoprostanes or as lipid hydroperoxides using specific HPLC techniques. Development of isoprostane measurement will advance specificity and precision. The measurement of oxidative damage to proteins has some potential but such methods have not been effectively exploited. (3) Epidemiological studies support the hypothesis that the major antioxidant nutrients vitamin E and vitamin C, and beta-carotene (which may or may not be acting as an antioxidant in vivo), may play a beneficial role in prevention of several chronic disorders. More research is needed on the impact of other non-nutrient compounds, such as other carotenoids and flavonoids, on human health. In general, human intervention studies using hard end-points are the gold standard. Trials are restricted mainly to the major antioxidants and do not allow firm conclusions because of inconsistent findings, an insufficient number of studies and the use of varying doses. There is evidence that large doses of beta-carotene may be deleterious to the health of certain subgroups of the population such as heavy habitual smokers. (4) With respect to the safety of administration of supplementary vitamins, vitamin C is safe at levels of supplementation up to 600 mg/d, and higher levels, up to 2000 mg/d, are without risk. Vitamin E has a very low human toxicity and an intake of 1000 mg/d is without risk; 3200 mg/d has been shown to be without any consistent risk. Large intakes of beta-carotene must be viewed with caution because they have been shown to confer detriment to a population at high risk of lung cancer when administered after many years of high risk (smoking) behaviour. Until further work clarifies the situation in heavy smokers with respect to taking supplements, larger doses should be avoided by such individuals. There is little reliable information about the human toxicology of flavonoids and related non-nutrient antioxidant constituents of the diet. (5) The food industry has long experience in the control of oxidative damage in foods and this experience can be used to advantage for the protection of food antioxidants which are beneficial. Some of these, such as vitamins C and E and beta-carotene, are well known, and strategies for their protection in foods are already exploited by food technologies. (ABSTRACT TRUNCATED)
Antioxidants↗
Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants.
The comparative mechanisms and relative rates of nitrogen dioxide (NO2.), thiyl (RS.) and sulphonyl (RSO2.) radical scavenging by the carotenoid antioxidants lycopene, lutein, zeaxanthin, astaxanthin and canthaxanthin have been determined by pulse radiolysis. All the carotenoids under study react with the NO2. radical via electron transfer to generate the carotenoid radical cation (Car.+). In marked contrast the glutathione and 2-mercaptoethanol thiyl radicals react via a radical addition process to generate carotenoid-thiyl radical adducts [RS-Car].. The RSO2. radical undergoes both radical addition, [RSO2-Car]. and electron abstraction, Car.+. Both carotenoid adduct radicals and radical cations decay bimolecularly. Absolute rate constants for radical scavenging were in the order of approximately 10(7)-10(9) M(-1) s(-1) and follow the sequence HO(CH2)2S. > RSO2. > GS. > NO2.. Although there were some discernible trends in carotenoid reactivity for individual radicals, rate constants varied by no greater than a factor of 2.5. The mechanism and rate of scavenging is strongly dependent on the nature of the oxidising radical species but much less dependent on the carotenoid structure.
Antioxidants↗
Non-oxidative modification of low density lipoprotein by ruptured myocytes.
In this study, the interaction of ruptured cardiac myocytes with low density lipoprotein (LDL) has been investigated and the consequent extent of uptake by macrophages. The results show that lysate released from ruptured myocytes is capable of inducing LDL oxidation and that the resulting modified form is recognised and degraded by macrophages. Peroxyl radical scavengers inhibit the LDL oxidation but not the macrophage uptake suggesting that LDL can be modified by mechanisms that are independent of oxidative processes by intracellular constituents of cardiac myocytes.
Animals↗
Measurement of the antioxidant status of dietary constituents, low density lipoproteins and plasma.
There is a considerable interest in antioxidants as bioactive components of food and as nutritional agents with a role in the maintenance of health and in disease prevention. There are situations in which knowledge of the individual levels of specific antioxidant components might be less useful than the total antioxidant potency of the medium concerned, the total antioxidant activity being determined by the combined reducing activities of its constituents. Such situations might be in the understanding of the structure-activity relationships of pure antioxidant compounds, in the determination of the antioxidant contributions of specific dietary components and how this relates to the antioxidant composition and activities of the individual constituents, and in the study of decreases in plasma antioxidant activity in individuals under oxidative stress in specific disease states. This article describes the application of the ABTS radical cation method to the measurement of the total antioxidant activity in order to address these questions.
Antioxidants↗
Serum total antioxidant activity after myocardial infarction.
Serum total antioxidant activity (TAA), albumin and uric acid were measured on admission, and for the next 2 days in 56 patients suffering myocardial infarction, 20 of whom received streptokinase. The 'antioxidant gap', the difference between the serum TAA and the sum of the serum albumin and uric acid activity, was calculated. No significant changes in serum total antioxidant activity were observed in either group of patients between admission, day 1 and day 2. However, a decline in the 'antioxidant gap' after myocardial infarction was associated with a significantly higher mortality.
Adult↗
The antioxidant properties of theaflavins and their gallate esters--radical scavengers or metal chelators?
The antioxidant properties of theaflavins and their gallate esters were studied by investigating their abilities to scavenge free radicals in the aqueous and lipophilic phases. The total relative antioxidant activities in the aqueous phase were assessed by measuring their direct ABTS.+ radical scavenging abilities, and by their efficacies in inhibiting the degradation of deoxyribose induced by iron. The propensities for enhancing the resistance of LDL to oxidation mediated by Cu2+ were also measured. The results show that the hierarchy of reactivity of these compounds as antioxidants is: theaflavin digallate > 3'-monogallate = 3-monogallate > theaflavin. Spectroscopic studies show that all the compounds chelate iron and copper; enhanced absorbance in the visible region is observed in the case of the iron-digallate complex, but not with copper.
Antioxidants↗
Differential distribution of ferulic acid to the major plasma constituents in relation to its potential as an antioxidant.
The hydroxycinnamates, intermediates in the phenylpropanoid synthetic pathway, are effective in enhancing the resistance of low-density lipoprotein (LDL) to oxidation in the order caffeic acid > ferulic acid > p-coumaric acid. It is unclear whether the mode of action of ferulic acid as an antioxidant is based on its activities in the aqueous or the lipophilic phase. Partitioning of 14C-labelled ferulic acid into plasma and its components, LDL and the albumin-rich fractions, has been studied under conditions of maximum aqueous solubility. The majority of ferulic acid associates with the albumin-rich fraction of the plasma, although a proportion is also found to partition between the LDL and aqueous phases; however, ferulic acid does not associate with the lipid portion of the LDL particle, suggesting that it exerts its antioxidant properties from the aqueous phase. This is of particular interest since the results demonstrate that ferulic acid is a more effective antioxidant against LDL oxidation than the hydrophilic antioxidant ascorbic acid.
Antioxidants↗