Evaluation of the Antioxidant Properties of Propofol and its Nitrosoderivative. Comparison with Homologue Substituted Phenols

Propofol (2,6-diisopropylphenol), some substituted phenols (2,6-dimethylphenol and 2,6-ditertbutylphenol) and their 4-nitrosoderivatives have been compared for their scavenging ability towards 1,1-diphenyl-2-picrylhydrazyl and for their inhibitory action on lipid peroxidation. These products were also compared to the classical antioxidants butylated hydroxytoluene and butylated hydroxyanisole. When measuring the reactivity of the various phenolic derivatives with 1,1-diphenyl-2-picrylhydrazyl the following order of effectiveness was observed: butylated hydroxyanisole>propofol>2,6-dimethylphenol>2,6-di-tertbutylphenol?>?butylated hydroxytoluene. In cumene hydroperoxide-dependent microsomal lipid peroxidation, propofol acts as the most effective antioxidant, while butylated hydroxyanisole, 2,6-di-tertbutylphenol and butylated hydroxytoluene exhibit a rather similar effect, although lower than propofol. In the iron/ascorbate-dependent lipid peroxidation propofol, at concentrations higher than 10?μM, exhibits antioxidant properties comparable to those of butylated hydroxytoluene and butylated hydroxyanisole. 2,6-Dimethylphenol is scarcely effective in both lipoperoxidative systems. The antioxidant properties of the various molecules depend on their hydrophobic characteristics and on the steric and electronic effects of their substituents. However, the introduction of the nitroso group in the 4-position almost completely removes the antioxidant properties of the examined compounds. The nitrosation of the aromatic ring of antioxidant molecules and the consequent loss of antioxidant capacity can be considered a condition potentially occurring in vivo since nitric oxide and its derivatives are continuously formed in biological systems.     

Antioxidative activity of thiophane [bis(3-(3,5-di-tret-butyl-4-hydroxyphenyl)propyl)sulfide]

The antioxidant activity, mutagenicity, and genotoxicity of bis(3-(3,5-di-tret-butyl-4-hydroxyphenyl)propyl)sulfide (thiophane) were studied using bacterial tests. The results of both an Ames test and SOS chromotest, as well as those studying the survival of E. coli cells deficient in enzymes responsible for the repair of DNA oxidative damage, testify to the fact that thiophane is not mutagenic and genotoxic, and it protects Salmonella typhimurium cells better than the well-known antioxidant trolox.     

Evaluation of the antioxidant properties of propofol and its nitrosoderivative. comparison with homologue substituted phenols

Propofol (2,6-diisopropylphenol), some substituted phenols (2,6-dimethylphenol and 2,6-ditertbutylphenol) and their 4-nitrosoderivatives have been compared for their scavenging ability towards 1,1-diphenyl-2-picrylhydrazyl and for their inhibitory action on lipid peroxidation. These products were also compared to the classical antioxidants butylated hydroxytoluene and butylated hydroxyanisole. When measuring the reactivity of the various phenolic derivatives with 1,1-diphenyl-2-picrylhydrazyl the following order of effectiveness was observed: butylated hydroxyanisole > propofol > 2,6-dimethylphenol > 2,6-di-tertbutylphenol > butylated hydroxytoluene. In cumene hydroperoxide-dependent microsomal lipid peroxidation, propofol acts as the most effective antioxidant, while butylated hydroxyanisole, 2,6-di-tertbutylphenol and butylated hydroxytoluene exhibit a rather similar effect, although lower than propofol. In the iron/ascorbate-dependent lipid peroxidation propofol, at concentrations higher than 10 microM, exhibits antioxidant properties comparable to those of butylated hydroxytoluene and butylated hydroxyanisole, 2,6-Dimethylphenol is scarcely effective in both lipoperoxidative systems. The antioxidant properties of the various molecules depend on their hydrophobic characteristics and on the steric and electronic effects of their substituents. However, the introduction of the nitroso group in the 4-position almost completely removes the antioxidant properties of the examined compounds. The nitrosation of the aromatic ring of antioxidant molecules and the consequent loss of antioxidant capacity can be considered a condition potentially occurring in vivo since nitric oxide and its derivatives are continuously formed in biological systems.     

Role of endogenous and exogenous antioxidants in the defence against functional damage and lipid peroxidation in rat liver mitochondria

Mitochondria are cellular organelles where the generation of reactive oxygen species may be high. They are, however, effectively protected by their high capacities of antioxidative systems, as enzymes and either water or lipid soluble low molecular weight antioxidants.These antioxidative defence systems can be effectively regenerated after or during an oxidative stress as long as the mitochondria are in an energized state. Energization of mitochondria mainly depends on the availability of suitable respiratory substrates which can provide hydrogen for the reduction of either the glutathione- or -tocopherol-system, since GSH is regenerated by glutathione reductase with the substrate NADPH and the -tocopheroxyl-radical likely by reduced coenzyme Q. It was shown that mitochondria do not undergo damages as long as they can keep a high energy state. The delicate balance between prooxidative/antioxidative activities can be shifted towards oxidation, if experimentally prooxidants were added. After exhaustion of the antioxidative defence systems damages of rnitochondrial functions become expressed followed by membrane injuries along with the oxidation and degradation of mitochondrial lipids and proteins leading finally to the total degradation of the mitoc hondria.Extramitochondrial antioxidants may assist the mitochondrial antioxidative defence systems in a complex way, whereby particularly ascorbic acid can act both as prooxidant and as antioxidant. (Mol Cell Biochem 174: 199–205, 1997)     

Antioxidative responses to mercury in the cell cultures of Sesbania drummondii.

The effect of mercury (Hg) on the growth and the response of antioxidative systems have been investigated in Sesbania cell cultures to determine the tolerance limits and the mechanisms of metal (Hg) tolerance in plant cells. Cell cultures of Sesbania were developed in different concentrations (0-50 microM) of mercury. Cultures tolerated Hg up to a concentration of 40 microM and showed an increase in the fresh weight growth by 620% in 3 weeks. The levels of antioxidants: glutathione (GSH) and non-protein thiols (NPSH) and the activities of antioxidative enzymes: superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11) and glutathione reductase (GR, EC 1.6.4.2) were influenced by Hg treatments. The contents of GSH, NPSH and GSH/GSSG ratio increased up to a concentration of 40 muM Hg and then severely declined at 50 microM Hg. The activities of antioxidative enzymes, SOD, APX and GR followed the same trends as antioxidants, first increased up to a concentration of 40 muM Hg and then declined in the presence of 50 microM Hg.     

Changes in Antioxidative Protection in Bean Cotyledons During Natural and Continuous Irradiation-Accelerated Senescence

We employed continuous irradiation (CL) for induction of premature senescence caused by enhanced production of reactive oxygen species. As a model plant we used bean (Phaseolus vulgaris L. cv. Jantar) cotyledons because they have well defined and a quite short life span. Senescence of bean cotyledons induced by CL progressed more rapidly than natural senescence: the life span of CL cotyledons was 13 d compared to 16 d in controls (C). Chl content was significantly lower in 10- and 13-d-old CL plants than in C plants and the change with age was not statistically significant. Activities of all antioxidative enzymes declined either with senescence onset or during whole life span. Activity of antioxidative enzymes, except ascorbate peroxidase, was lower in CL plants compared to C plants. On the contrary, contents of non-enzymatic antioxidants -carotene and ascorbate were higher in CL plants than in C plants. No significant difference, except in the youngest cotyledons, was observed in glutathione content.     

Effect of antioxidants on the status of the antioxidative system in cerebral ischemia and reperfusion injury

Protective effects of ionol, o-benzoquinone-2 and ascorbic acid, their influence on the activity of antioxidative enzymes, the level of diene conjugates (DC) and of recovered glutathione in the mitochondrial fraction in the case of ischemic and reperfusion injury of the brain have been investigated. An increase in the activity of the antioxidative system enzymes during the post-ischemic period induced probably by the accumulated products of lipid peroxidation is shown: glutathione peroxidase (EC 1.11.1.9)--by 159%, glutathione reductase (EC 1.6.4.2)--by 26%, catalase (EC 1.11.1.6)--by 79%. This effect was not observed after introduction of antioxidants lowering the DC-level. It is concluded that antihypoxic action of the investigated antioxidants providing the survival of animals not only after the 5 min total circulatory ischemia but also after the 15 min one is caused by their antiradical properties and is not connected with stimulation of activity of enzymes supporting peroxidative homeostasis.     

Effect of phytyl side chain of vitamin E on its antioxidant activity

Inhibition of the oxidation of methyl linoleate and soybean phosphatidylcholine in homogeneous solution and in aqueous dispersion by four chain-breaking antioxidants, vitamin E (alpha-tocopherol), 2,2,5,7,8-pentamethyl-6-chromanol, 2,6-di-tert-butyl-4-methylphenol, and stearyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, was studied to examine the effect of the phytyl side chain of vitamin E on its antioxidant activity. These four antioxidants exerted similar antioxidative activities. They were also effective as antioxidants in protecting the oxidation of soybean phosphatidylcholine liposomes in water dispersion. However, when they were incorporated into dimyristoyl phosphatidylcholine liposomes, only 2,2,5,7,8-pentamethyl-6-chromanol and 2,6-di-tert-butyl-4-methylphenol could suppress the oxidation of soybean phosphatidylcholine liposomes dispersed in the same aqueous system. It was concluded that the antioxidative properties of vitamin E and its model without the phytyl side chain are quite similar within micelles and liposomes as well as in homogeneous solution but that the phytyl side chain enhances the retainment of vitamin E in liposomes and suppresses the transfer of vitamin E between liposomal membranes.     

抗氧化剂辅助疗法对光动力疗法疗效的影响

研究食物中含有的天然抗氧化剂对光动力疗法治疗效果的影响。通过在常规培养的K562细胞悬浮液中分别加入染料木素、鞣花酸、山竹黄酮这几种天然抗氧剂,用戊氨基乙酰丙酸-光动力疗法（ALA—PDT）作用后,检测各组细胞的存活率。研究发现染料木素、鞣花酸、山竹黄酮均可以提高光动力疗法的疗效。研究结果表明,抗氧化剂疗法和光动力疗法相互结合能够起到良好的治疗效果。     

Peroxisomes from pepper fruits (Capsicum annuum L.): purification, characterisation and antioxidant activity

Pepper is a vegetable of importance in human nutrition. Currently, one of the most interesting properties of natural products is their antioxidant content. In this work, the purification and characterisation of peroxisomes from fruits of a higher plant was carried out, and their antioxidative enzymatic and non-enzymatic content was investigated. Green and red pepper fruits (Capsicum annuum L., type Lamuyo) were used in this study. The analysis by electron microscopy showed that peroxisomes from both types of fruits contained crystalline cores which varied in shape and size, and the presence of chloroplasts and chromoplasts in green and red pepper fruits, respectively, was confirmed.

Peroxisomes were purified by differential and sucrose density-gradient centrifugations. In the peroxisomal fractions, the activity of the photorespiration, β-oxidation and glyoxylate cycle enzymes, and the ROS-related enzymes catalase, superoxide dismutase, xanthine oxidase, glutathione reductase and NADP⁺-dehydrogenases, was determined. Most enzymes studied had higher specific activity and protein content in green than in red fruits. By native PAGE and western blot analysis, the localisation of a Mn-SOD in fruit peroxisomes was demonstrated. The ascorbate and glutathione levels were also determined in crude extracts and in peroxisomes purified from both green and red peppers. The total ascorbate content (200-220 mg per 100 g FW) was similar in crude extracts from the two types of fruits, but higher in peroxisomes from red peppers. The glutathione concentration was 2-fold greater in green pepper crude extracts than in red fruits, whereas peroxisomes from both tissues showed similar values. The presence in pepper peroxisomes of different antioxidative enzymes and their corresponding metabolites implies that these organelles might be an important pool of antioxidants in fruit cells, where these enzymes could also act as modulators of signal molecules (O₂^˙-, H₂O₂) during fruit maturation.     

Antioxidative property of T-0970, a new ureidophenol derivative

We investigated the antioxidative property of T-0970, a newly synthesized ureidophenol derivative. The inhibitory effect of T-0970 on spontaneous lipid peroxidation in rat brain was 10 times greater than those of well-known antioxidants such as butylhydroxytoluene (BHT), probucol and α-tocopherol. T-0970 also showed dose-dependent free radical scavenging activities in vitro for both superoxide anions and hydroxyl radicals. The radical-scavenging potencies of T-0970 were about 10–30 times stronger than those of BHT. We evaluated the in vivo antioxidative ability of T-0970 in the animal model of acute oxidative tissue injury in rats. Intraperitoneal injection of ferric nitrilotriacetate (Fe/NTA) caused an acute and remarkable increase in the level of thiobarbituric acid-reactive substances (TBARS) in both plasma and the liver, and also resulted in a considerable elevation of the plasma levels of GOT and GPT indicative of hepatic injury. Both oral and intravenous administration of T-0970 dose-dependently depressed these diagnostic parameters. These results indicate that T-0970 may have a therapeutic potential in various diseases associated with oxidative tissue injury.     

Protective Effects of Selol Against Sodium Nitroprusside-Induced Cell Death and Oxidative Stress in PC12 Cells

Selol is an organic selenitetriglyceride formulation containing selenium at +4 oxidation level that can be effectively incorporated into catalytic sites of of Se-dependent antioxidants. In the present study, the potential antioxidative and cytoprotective effects of Selol against sodium nitroprusside (SNP)-evoked oxidative/nitrosative stress were investigated in PC12 cells and the underlying mechanisms analyzed. Spectrophoto- and spectrofluorimetic methods as well as fluorescence microscopy were used in this study; mRNA expression was quantified by real-time PCR. Selol dose-dependently improved the survival and decreased the percentage of apoptosis in PC12 cells exposed to SNP. To determine the mechanism of this protective action, the effect of Selol on free radical generation and on antioxidative potential was evaluated. Selol offered significant protection against the elevation of reactive oxidative species (ROS) evoked by SNP. Moreover, this compound restored glutathione homeostasis by ameliorating the SNP-evoked disturbance of GSH/GSSG ratio. The protective effect exerted by Selol was associated with the prevention of SNP-mediated down-regulation of antioxidative enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR), and thioredoxin reductase (TrxR). Finally, GPx inhibition significantly abolished the cytoprotective effect of Selol. In conclusion, these results suggest that Selol effectively protected PC12 cells against SNP-induced oxidative damage and death by adjusting free radical levels and antioxidant system, and suppressing apoptosis. Selol could be successfully used in the treatments of diseases that involve oxidative stress and resulting apoptosis.     

Copper-induced peroxidation of phosphatidylserine-containing liposomes is inhibited by nanomolar concentrations of specific antioxidants

Copper-induced peroxidation of liposomal palmitoyllinoleoyl-phosphatidylcholine (PLPC) is inhibited by -tocopherol at micromolar concentrations. In our previous study we found that when the liposomes contain phosphatidylserine (PS), nanomolar concentrations of Toc were sufficient to inhibit peroxidation. In an attempt to gain understanding of the origin of this extreme antioxidative potency, we tested the antioxidative potency of 36 additional antioxidants and the dependence of their potency on the presence of PS in the liposomes. The results of these studies reveal that only 11 of the tested antioxidants possess similar antioxidative potency to that of Toc. These include trolox, butylated hydroxytoluene (BHT), curcumin, nordihydroguaiaretic acid (NDGA), diethylstilbestrol (DES), 2 of the 13 tested flavonoids (luteolin and 7,3′,4′-trihydroxyflavone; T-414), -naphthol, 1,5-, 1,6- and 1,7-dihydroxynaphthalenes (DHNs). Propyl gallate (PG), methyl syringate, rosmarinic acid, resveratrol, other flavonoids, as well as β-naphthol, 1,2-, 1,3-, 1,4-, 2,3-, 2,6-, and 2,7-DHNs were either moderately antioxidative or pro-oxidative. For liposomes made of PLPC (250 μM) and PS (25 μM) the “lag” preceding copper-induced peroxidation (5 μM copper) was doubled upon addition of 30–130 nM of the “super-active” antioxidants.

We propose that the mechanism responsible for the extreme antioxidative potency against copper-induced peroxidation in PS-containing liposomes involves replenishment of the antioxidant in a ternary PS–copper-antioxidant complex. Based on structure–activity relationship of the 37 tested antioxidants, the “super-antioxidative potency” is attributed to the recycling of relatively stable semiquinone or semiquinone-like radicals.     

Natural antioxidants attenuate mycolactone toxicity to RAW 264.7 macrophages

Mycobacterium ulcerans produces a macrolide exotoxin, mycolactone which suppresses immune cells activity, is toxic to most cells and the key virulence factor in the pathogenesis of Buruli ulcer disease. Mycolactone is reported to mediate the production of reactive oxygen species in keratinocytes; cells that play critical role in wound healing. Increased levels of reactive oxygen species have been shown to disrupt the well-ordered process of wound repair; hence, the function of wound-healing cells such as macrophages, keratinocytes, and fibroblast could be impaired in the presence of the reactive oxygen species mediator, mycolactone. To ensure regeneration of tissues in chronic ulcers, with proper and timely healing of the wounds, natural antioxidants that can combat the effects of induced reactive oxygen species in wound-healing cells ought to be investigated. Reactive oxygen species activity was determined in mycolactone-treated RAW 264.7 macrophages and the scavenging ability of the antioxidants (ascorbic acid, gallic acid, and green tea kombucha) against mycolactone-induced reactive oxygen species (superoxide anions) was assessed using fluorescein probe (DCF-DA) and nitroblue tetrazolium dye. Cytotoxicity of the antioxidants, mycolactone, and the protective effect of the antioxidants on the cells upon treatment with mycolactone were determined using the Alamar blue assay. The expression levels of endogenous antioxidant enzyme genes (superoxide dismutase, catalase, and glutathione peroxidase) in response to mycolactone-mediated reactive oxygen species were determined using RT-qPCR. Mycolactone induced the production of reactive oxygen species in RAW 264.7 macrophages, and the resulting superoxide anions were scavenged by some of the antioxidants. The selected endogenous antioxidant enzyme genes in the macrophages were upregulated in the presence of the antioxidants and mycolactone. The exogenously supplied ascorbic acid and green tea kombucha offered moderate protection to the macrophages against the toxicity of mycolactone. We conclude that the results provide insights into alternate and adjunct therapeutic approaches in Buruli ulcer treatment, which could significantly attenuate the toxicity of the pathogenic factor; mycolactone.     

Some physiological and biochemical aspects of plant resistance to cadmium effect. I. Antioxidative system

The hitherto studies on the effect of cadmium on plants have shown that it causes intensification of two types of unfavorable processes in plants: inactivation of macromolecules and cellular structures and induction of oxidative stress. In response, the plant organism activates processes restoring its homeostasis, i.e. those which remove reversible and irreversible changes. In removing the former a particular role is played by the antioxidative system containing enzymatic and nonenzymatic antioxidants, and removing the active forms of oxygen. The strategy of stress tolerance plays an important role in the plant resistance to cadmium and other toxic metals.     

Bacterial Metabolism of 2,6-Xylenol

Strain DM1, a Mycobacterium sp. that utilizes 2,6-xylenol, 2,3,6-trimethylphenol, and o-cresol as sources of carbon and energy, was isolated. Intact cells of Mycobacterium strain DM1 grown with 2,6-xylenol cooxidized 2,4,6-trimethylphenol to 2,4,6-trimethylresorcinol. 4-Chloro-3,5-dimethylphenol prevents 2,6-xylenol from being totally degraded; it was quantitatively converted to 2,6-dimethylhydroquinone by resting cells. 2,6-Dimethylhydroquinone, citraconate, and an unidentified metabolite were detected as products of 2,6-xylenol oxidation in cells that were partially inactivated by EDTA. Under oxygen limitation, 2,6-dimethylhy-droquinone, citraconate, and an unidentified metabolite were released during 2,6-xylenol turnover by resting cells. Cell extracts of 2,6-xylenol-grown cells contained a 2,6-dimethylhydroquinone-converting enzyme. When supplemented with NADH, cell extracts catalyzed the reduction of 2,6-dimethyl-3-hydroxyquinone to 2,6-dimethyl-3-hydroxyhydroquinone. Since a citraconase was also demonstrated in cell extracts, a new metabolic pathway with 2,6-dimethyl-3-hydroxyhydroquinone as the ring fission substrate is proposed.     

Propofol hemisuccinate protects neuronal cells from oxidative injury

Oxidative stress contributes to the neuronal death observed in neurodegenerative disorders and neurotrauma. Some antioxidants for CNS injuries, however, have yet to show mitigating effects in clinical trials, possibly due to the impermeability of antioxidants across the blood-brain barrier (BBB). Propofol (2,6-diisopropylphenol), the active ingredient of a commonly used anesthetic, acts as an antioxidant, but it is insoluble in water. Therefore, we synthesized its water-soluble prodrug, propofol hemisuccinate sodium salt (PHS), and tested for its protective efficacy in neuronal death caused by non-receptor-mediated, oxidative glutamate toxicity. Glutamate induces apoptotic death in rat cortical neurons and the mouse hippocampal cell line HT-22 by blocking cystine uptake and causing the depletion of intracellular glutathione, resulting in the accumulation of reactive oxygen species (ROS). PHS has minimal toxicity and protects both cortical neurons and HT-22 cells from glutamate. The mechanism of protection is attributable to the antioxidative property of PHS because PHS decreases the ROS accumulation caused by glutamate. Furthermore, PHS protects HT-22 cells from oxidative injury induced by homocysteic acid, buthionine sulfoximine, and hydrogen peroxide. For comparison, we also tested alpha-tocopherol succinate (TS) and methylprednisolone succinate (MPS) in the glutamate assay. Although TS is protective against glutamate at lower concentrations than PHS, TS is toxic to HT-22 cells. In contrast, MPS is nontoxic but also nonprotective against glutamate. Taken together, PHS, a water-soluble prodrug of propofol, is a candidate drug to treat CNS injuries owing to its antioxidative properties, low toxicity, and permeability across the BBB.     

Nitric oxide alleviates manganese toxicity by preventing oxidative stress in excised rice leaves

In the present study, we have investigated the effects of nitric oxide (NO) on alleviating manganese (Mn)-induced oxidative stress in rice leaves. Exogenous MnCl₂ treatment to excised rice leaves for 24 and 48 h resulted in increased production of H₂O₂ and lipid peroxides, decline in the levels of antioxidants, glutathione and ascorbic acid, and increased activities of antioxidative enzymes, superoxide dismutase, guaiacol peroxidase, catalase, ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase. Treatment of rice leaves with 100 μM sodium nitroprusside (SNP), a NO donor, was effective in reducing Mn-induced increased levels of H₂O₂, lipid peroxides and increased activities of antioxidative enzymes. The levels of reduced ascorbate and glutathione were considerably recovered due to SNP treatment. The effect of SNP was reversed by the addition of NO scavenger, 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (c-PTIO) suggesting that ameliorating effect of SNP is due to release of NO. The results indicate that MnCl₂ induces oxidative stress in excised rice leaves, lowers the levels of reduced ascorbate and glutathione, and elevates activities of the key antioxidative enzymes. NO appears to provide a protection to the rice leaves against Mn-induced oxidative stress and that exogenous NO application could be advantageous in combating the deleterious effects of Mn-toxicity in rice plants.     

Effects of speciation on partitioning of iodine in aqueous biphasic systems and onto ABEC resins

Polyethylene glycol (PEG)-aqueous biphasic systems (ABS) and PEG-grafted aqueous biphasic extraction chromatographic (ABEC) resins have been shown to remove inorganic species from environmental and nuclear wastes. The partitioning behavior of several iodide species (iodide, iodine, triiodide, iodate, and 4-iodo-2,6-dimethylphenol (I-DMP)) have been studied for PEG (MW 2000)-salt systems and ABEC resins. Iodide partitioning to PEG-rich phases or onto ABEC resins can be enhanced by derivatization with 2,6-dimethylphenol to form 4-iodo-2,6-dimethylphenol or by addition of I(2) to form triiodide. Conversely, iodide partitioning to the PEG-rich phase or onto ABEC resins is reduced by oxidation of iodide to IO(3)(-). Partitioning studies of iodide, iodate, and iodine in a PEG-ABS are compared to results using ABEC resins.     

Antioxidants; not the only reason to eat fruit and vegetables

There is a considerable body of evidence, from epidemiology, that fruits and vegetables help to prevent cancer. This is commonly attributed to the antioxidants that they contain, which are supposed to decrease cancer risk by protecting DNA against oxidative damage. It is certainly true that individual antioxidants, such as vitamin C, vitamin E (α-tocopherol) and carotenoids can decrease oxidative damage to DNA, in in vitro model systems, in cultured cells, and in humans given supplements. Real foods, including fried onions, carrot juice, soya milk and kiwifruit also decrease DNA oxidation in human lymphocytes tested ex vivo. The significance of these effects has to be examined in the light of revised estimates of the level of background damage in normal cells; this is hundreds of times less than has been suggested in the past. Other effects of phytochemicals found in these foods are potentially important, such as the enhancement or inhibition of phase I and phase II metabolising enzymes, and modulation of DNA repair. This revised version was published online in June 2006 with corrections to the Cover Date.