Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms.
TL;DR: Three structural requirements of flavonoids for protection from glutamate are the hydroxylated C3, an unsaturated C ring, and hydrophobicity, and three distinct mechanisms of protection are found, which show that the mechanism of protection from oxidative insults by flavonoid is highly specific for each compound.
About: This article is published in Free Radical Biology and Medicine.The article was published on 2001-02-15. It has received 804 citations till now. The article focuses on the topics: Oxidative stress & Glutathione.
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TL;DR: Methods available for the measurement of antioxidant capacity are reviewed, presenting the general chemistry underlying the assays, the types of molecules detected, and the most important advantages and shortcomings of each method.
Abstract: Methods available for the measurement of antioxidant capacity are reviewed, presenting the general chemistry underlying the assays, the types of molecules detected, and the most important advantages and shortcomings of each method. This overview provides a basis and rationale for developing standardized antioxidant capacity methods for the food, nutraceutical, and dietary supplement industries. From evaluation of data presented at the First International Congress on Antioxidant Methods in 2004 and in the literature, as well as consideration of potential end uses of antioxidants, it is proposed that procedures and applications for three assays be considered for standardization: the oxygen radical absorbance capacity (ORAC) assay, the Folin-Ciocalteu method, and possibly the Trolox equivalent antioxidant capacity (TEAC) assay. ORAC represent a hydrogen atom transfer (HAT) reaction mechanism, which is most relevant to human biology. The Folin-Ciocalteu method is an electron transfer (ET) based assay and gives reducing capacity, which has normally been expressed as phenolic contents. The TEAC assay represents a second ET-based method. Other assays may need to be considered in the future as more is learned about some of the other radical sources and their importance to human biology.
4,580 citations
TL;DR: Plant-derived phenolics represents good sources of natural antioxidants, however, further investigation on the molecular mechanism of action of these phytochemicals is crucial to the evaluation of their potential as prophylactic agents.
Abstract: Accumulating chemical, biochemical, clinical and epidemiological evidence supports the chemoprotective effects of phenolic antioxidants against oxidative stress-mediated disorders. The pharmacological actions of phenolic antioxidants stem mainly from their free radical scavenging and metal chelating properties as well as their effects on cell signaling pathways and on gene expression. The antioxidant capacities of phenolic compounds that are widely distributed in plant-based diets were assessed by the Trolox equivalent antioxidant capacity (TEAC), the ferric reducing antioxidant power (FRAP), the hypochlorite scavenging capacity, the deoxyribose method and the copper-phenanthroline-dependent DNA oxidation assays. Based on the TEAC, FRAP and hypochlorite scavenging data, the observed activity order was: procyanidin dimer>flavanol>flavonol>hydroxycinnamic acids>simple phenolic acids. Among the flavonol aglycones, the antioxidant propensities decrease in the order quercetin, myricetin and kaempferol. Gallic acid and rosmarinic acid were the most potent antioxidants among the simple phenolic and hydroxycinnamic acids, respectively. Ferulic acid displayed the highest inhibitory activity against deoxyribose degradation but no structure-activity relationship could be established for the activities of the phenolic compounds in the deoxyribose assay. The efficacies of the phenolic compounds differ depending on the mechanism of antioxidant action in the respective assay used, with procyanidin dimers and flavan-3-ols showing very potent activities in most of the systems tested. Compared to the physiologically active (glutathione, alpha-tocopherol, ergothioneine) and synthetic (Trolox, BHA, BHT) antioxidants, these compounds exhibited much higher efficacy. Plant-derived phenolics represents good sources of natural antioxidants, however, further investigation on the molecular mechanism of action of these phytochemicals is crucial to the evaluation of their potential as prophylactic agents.
1,293 citations
TL;DR: The most popular methods for determining chain-breaking antioxidant activity (AOA) of food are considered with the aim to estimate their reliability and limitations in this paper, where the main requirements imposed on these methods have been suggested.
787 citations
TL;DR: It is shown here that nanoparticles composed of cerium oxide or yttrium oxide protect nerve cells from oxidative stress and that the neuroprotection is independent of particle size.
708 citations
Cites background or methods from "Flavonoids protect neuronal cells f..."
...These alternatives were sequentially ruled out by published procedures [25]....
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...The ability to sequester accumulated ROS is perhaps the best way to assay for direct antioxidant activity in intact cells [25]....
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...A lower level of ROS shows that the compound is acting as a direct antioxidant since the time frame is too short to induce any significant antioxidant response [25]....
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...oxygen species (ROS) was determined with dichlorofluorescein-di-acetate (H2DCF-dA) [25]....
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TL;DR: By phylogenetic analysis, it is shown that system x(c)(-) is a rather evolutionarily new amino acid transport system and its diverse roles in the regulation of the immune response, in various aspects of cancer and in the eye and the CNS are highlighted.
Abstract: The antiporter system xc− imports the amino acid cystine, the oxidized form of cysteine, into cells with a 1:1 counter-transport of glutamate. It is composed of a light chain, xCT, and a heavy chain, 4F2 heavy chain (4F2hc), and, thus, belongs to the family of heterodimeric amino acid transporters. Cysteine is the rate-limiting substrate for the important antioxidant glutathione (GSH) and, along with cystine, it also forms a key redox couple on its own. Glutamate is a major neurotransmitter in the central nervous system (CNS). By phylogenetic analysis, we show that system xc− is a rather evolutionarily new amino acid transport system. In addition, we summarize the current knowledge regarding the molecular mechanisms that regulate system xc−, including the transcriptional regulation of the xCT light chain, posttranscriptional mechanisms, and pharmacological inhibitors of system xc−. Moreover, the roles of system xc− in regulating GSH levels, the redox state of the extracellular cystine/cysteine re...
631 citations
Cites background from "Flavonoids protect neuronal cells f..."
...In a related study, flavonoids, natural plant compounds, were investigated (99)....
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References
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TL;DR: The factors underlying the influence of the different classes of polyphenols in enhancing their resistance to oxidation are discussed and support the contention that the partition coefficients of the flavonoids as well as their rates of reaction with the relevant radicals define the antioxidant activities in the lipophilic phase.
8,513 citations
TL;DR: It is argued that this damage to DNA, protein, and lipid is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts.
Abstract: Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great.
6,007 citations
TL;DR: The use of the foregoing analytical method in the determination of total and oxidized glutathione contents of rat blood, kidney, and liver gave values in good agreement with those obtained by previous investigators.
5,900 citations
"Flavonoids protect neuronal cells f..." refers methods in this paper
...Upon neutralization of the supernatants with triethanolamine, the concentration of total glutathione (reduced and oxidized) was determined by the method described originally by Tietze [50] and modified by Griffith [51]....
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TL;DR: Flavonoids in regularly consumed foods may reduce the risk of death from coronary heart disease in elderly men and showed an inverse relation with incidence of myocardial infarction.
4,440 citations
"Flavonoids protect neuronal cells f..." refers background in this paper
...Indeed, flavonoids and other plant-derived polyphenolic compounds have recently captured public interest because flavonoids in tea, fruits, and vegetables reduce the risk of cardiovascular diseases [13,14]....
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TL;DR: It is reported here that 2-vinylpyridine is a much better reagent for the derivitization of glutathione, and it is demonstrated that the total glutATHione concentration in mouse plasma is substantially higher than generally reported and that glutathion disulfide constitutes less than 30% of the totalglutathione present.
4,279 citations