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Free radicals and antioxidants are widely discussed in the clinical and nutritional literature. Antioxidants are needed to prevent the formation and oppose the actions of reactive oxygen and nitrogen species, which are generated in vivo and cause damage to DNA, lipids, proteins, and other biomolecules. Endogenous antioxidant defenses (superoxide dismutases, H 2 O 2 -removing enzymes, metal binding proteins) are inadequate to prevent damage completely, so dietderived antioxidants are important in maintaining health. Many dietary compounds have been suggested to be important antioxidants: The evidence for a key role of vitamins E and C is strong, but that for carotenoids and related plant pigments is weaker. Interest is also growing in the role of plant phenolics, especially flavonoids. Some antioxidants can exert prooxidant effects in vitro, but their physiological relevance is uncertain. Experimental approaches to the optimization of antioxidant nutrient intake are proposed.
The role of antioxidants in nutrition is an area of increasing interest. Antioxidants are used (1) to prolong the shelf life and maintain the nutritional quality of lipid-containing foods, and (2) to modulate the consequences of oxidative damage in the human body. This review discusses what an antioxidant is and how the properties of antioxidants may be characterized.
Damage to the bases in DNA produced by the hypoxanthine/xanthine oxidase system in the presence of iron ions was studied. The base products in DNA were measured using gas chromatography-mass spectrometry with selected ion monitoring after acidic hydrolysis of DNA and trimethylsilylation. Products identified were cytosine glycol, thymine glycol, 5,6-dihydroxycytosine, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 8-hydroxyguanine. These are typical hydroxyl radical-induced products of the bases in DNA. 2,6-Diamino-4-hydroxy-5-formamidopyrimidine was the major product, followed by 8-hydroxyguanine, in DNA treated with hypoxanthine/xanthine oxidase/Fe3+-EDTA. The use of Fe3+ did not cause as much damage to the bases in DNA as did the use of Fe3+-EDTA. In both systems, the formation of the products was inhibited by superoxide dismutase, catalase, dimethyl sulfoxide, mannitol, and desferrioxamine, but inhibitions were much stronger in the systems containing EDTA. Hence formation of hydroxyl radicals by a superoxide radical-assisted Fenton reaction is proposed to account for the results obtained. 2,6-Diamino-4-hydroxy-5-formamidopyrimidine, 5,6-dihydroxycytosine, 4,6-diamino-5-formamidopyrimidine, and 8-hydroxyguanine were proposed as the products in DNA to measure if one aims to measure DNA products as indices of oxidative DNA damage involving hydroxyl radicals in vivo.
Uric acid is an end-product of purine metabolism in Man, and has been suggested to act as an antioxidant in vivo. Products of attack upon uric acid by various oxidants were measured by high performance liquid chromatography. Hypochlorous acid rapidly oxidized uric acid, forming allantoin, oxonic/oxaluric and parabanic acids, as well as several unidentified products. HOCl could oxidize all these products further. Hydrogen peroxide did not oxidize uric acid at detectable rates, although it rapidly oxidized oxonic acid and slowly oxidized allantoin and parabanic acids. Hydroxyl radicals generated by hypoxanthine/xanthine oxidase or Fe2+-EDTA/H2O2 systems also oxidized uric acid to allantoin, oxonic/oxaluric acid and traces of parabanic acid. Addition of ascorbic acid to the Fe2+-EDTA/H2O2 system did not increase formation of oxidation products from uric acid, possibly because ascorbic acid can ‘repair’ the radicals resulting from initial attack of hydroxyl radicals upon uric acid. Mixtures of methaemoglobin or metmyoglobin and H2O2 also oxidized uric acid: allantoin was the major product, but some parabanic and oxonic/oxaluric acids were also produced. Caeruloplasmin did not oxidize uric acid under physiological conditions, although simple copper (Cu2+) ions could, but this was prevented by albumin or histidine. The possibility of using oxidation products of uric acid, such as allantoin, as an index of oxidant generation in vivo in humans is discussed.
No abstract is provided for this article.
The iron chelator desferal is a powerful inhibitor of lipid peroxidation and of hydroxyl radical formation dependent on the presence of iron salts. Desferal also reacts with Superoxide radical with a second-order rate constant approximately equal to 3 × 102 M−1 at pH 10.2 and approximately 9 × 102 M−1 s−1 at physiological pH. It is concluded that this slow reaction of desferal with O2 − is unlikely to influence the interpretation of experiments in which the chelator is used. The ability of desteral to react with hydroxyl radical (k2 approximately 1010M−1s−1) is a far more likely source of error in the interpretation of results using this chelating agent.
Reactive oxygen species are constantly formed in the human body and removed by antioxidant defenses. An antioxidant is a substance that, when present at low concentrations compared to that of an oxidizable substrate, significantly delays or prevents oxidation of that substrate. Antioxidants can act by scavenging biologically important reactive oxygen species (O2 − ·, H2O2, · OH, HOCl, ferryl, peroxyl, and alkoxyl), by preventing their formation, or by repairing the damage that they do. One problem with scavenging-type antioxidants is that secondary radicals derived. from them can often themselves do biologic damage. These various principles will be illustrated by considering several thiol compounds.
No abstract is provided for this article.
Abstract This chapter defines the term 'antioxidant', explains the different mechanisms of antioxidant action, and describes the antioxidants synthesized by living organisms: how they are made, how they work, and their importance in vivo. One defence is to control exposure to O2, as illustrated by stem cells and nitrogen fixation. Antioxidants described in detail include the superoxide dismutases (CuZnSOD, mitochondrial MnSOD, FeSOD, NiSOD, cambialistic SODs), how to measure their activity, and why superoxide is damaging (direct toxicity, H2O2, hydroxyl radical, and peroxynitrite formation). Glutathione, the enzymes that synthesize and degrade it (γ-glutamylcysteine synthetase, glutathione synthetase and γ-glutamyl transpeptidase), and those that use it (e.g. glutathione peroxidases, glutathione-S-transferases, glyoxalases), are described. Superoxide reductases, thioredoxins, peroxiredoxins, catalase, other peroxidases (especially ascorbate, cytochrome c, and horseradish peroxidases), trypanothione, mycothiol, bacillithiol, homoglutathione, haem oxygenases (HO-1 and HO-2), metallothioneins, albumin, sulphiredoxins, oestradiol, melatonin, ergothioneine, tryparedoxin, ovothiols, carnosine, homocarnosine, lipoic acid, mycosporine-glycine, urate, melanin, bilirubin, Mn2+ as a replacement for SOD and a constituent of some catalases, pyruvate, coenzyme Q, and trehalose are reviewed as putative antioxidants in vivo. The roles of peroxiredoxins, catalase, and glutathione peroxidases in removing H2O2, and how they co-operate with SODs, is discussed. Selenium, iron, and copper metabolism are presented in relation to antioxidant defence, and to deficiency and overload diseases such as Wilson disease and haemochromatosis. Regulation of body iron and copper stores is explained in relation to the need to prevent oxidative damage, including methods to detect the labile iron pool. The relation of gender to antioxidant defence is discussed.
Conference Article| November 01 1996 Free radicals, proteins and DNA: oxidative damage versus redox regulation B. Halliwell B. Halliwell 1Neurodegenerative Disease Research Centre, King's College, Manresa Road, London SW3 6LX, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1996) 24 (4): 1023–1027. https://doi.org/10.1042/bst0241023 Article history Received: June 07 1996 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation B. Halliwell; Free radicals, proteins and DNA: oxidative damage versus redox regulation. Biochem Soc Trans 1 November 1996; 24 (4): 1023–1027. doi: https://doi.org/10.1042/bst0241023 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: ROS, reactive oxygen species, RNS, reactive nitrogen species This content is only available as a PDF. © 1996 Biochemical Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.
