B Halliwell

..Cell death has some features of apoptosis (propidium iodide staining, externalization of phosphatidylserine, limited caspase-3 and -9 activities), but there was no internucleosomal DNA fragmentation...

..We conclude that DSS decreases lipid peroxidation in vivo. However, oxidative damage biomarkers changed after the placebo meal, a phenomenon to consider when designing interventional studies...

..Increasing endogenous antioxidant levels (e.g., by supplying "pro-oxidants") may be a better approach to therapeutics and disease prevention than consuming large doses of "dietary antioxidants."..

..Many studies of the biological effects of polyphenols in cell culture have been affected by their ability to oxidise in culture media, and awareness of this problem can avoid erroneous claims...

..This brief review attempts to define them and to examine the ways in which oxidative stress and oxidative damage can affect cell behaviour both in vivo and in cell culture, using cancer as an example...

..The emphasis throughout is on the caution that is needed in applying these methods in view of possible errors and artifacts in interpreting the results...

..Animal studies also support its usefulness. The weight of evidence available supports the suggestion that a major double-blind controlled clinical trial of antioxidants in prevention and treatment of type 2 diabetes should be undertaken...

..Our data show that the extract obtained from the seeds of Psoralea corylifolia L. decreased mitochondrial complex I and proteasome activities; and oxidative stress might be an early event...

..Such artefacts may have affected many studies on the effects of ascorbate, thiols, flavonoids and other polyphenolic compounds on cells in culture...

..Chronic inflammation predisposes to malignancy, but the role of RS in this is likely to be complex because RS can sometimes act as anti-inflammatory agents...

..The overall health benefit of flavonoids is uncertain, and consumption of large quantities of them in fortified foods or supplements should not yet be encouraged...

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..Recently, however, we have learned that they can also be anti-inflammatory by modulating the immune response. These data have implications for the proposed use of antioxidants to treat inflammation...

..We argue that tocopherols and tocotrienols may also exert direct beneficial effects in the gastrointestinal tract and that their return to the gastrointestinal tract by the liver through the bile may be physiologically advantageous...

..Work is underway to compare H(2)O(2) levels with variations in other biomarkers of oxidative damage, to test the possibility that there are daily or other periodic variations in oxidative damage rates...

..Thus, agents that increase proteasome function may be generally neuroprotective, as may be NOS inhibitors. Proteasome inhibitors should be used with caution as therapeutic agents...

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..The available evidence suggests that in Western populations, intake of certain fruit and vegetables can decrease oxidative DNA damage, whereas ascorbate, vitamin E, and beta-carotene cannot...

..This brief commentary highlights in broad terms the current status of the redox biology field and the major challenges it faces in the next decade...

..Urinary H(2)O(2) levels are influenced by diet, but under certain conditions might be a valuable biomarker of 'oxidative stress'...

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..Although there is no evidence that any of these effects are deleterious to humans, we might need to change our thinking about the mechanisms of the antioxidant action of ascorbate in vivo...

..It appears that such damage can be modulated by vegetable intake, although the effects of vegetables may be mediated by components different from the "classical" antioxidants vitamin C, alpha-tocopherol and beta-carotene...

..Several agents already in therapeutic use might exert some of their effects by antioxidant action, including selegiline (deprenyl), apomorphine and nitecapone...

..It was an exciting field when I started some 40 years ago, and it still is today, but some major challenges must be faced...

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..The association of neuronal apoptosis with oxidative stress and Abeta accumulation may provide clues to the pathogenesis of Alzheimer's disease, as well as the role oxidative stress plays in other neurodegenerative diseases...

..This shows that cPLA(2) plays an important role in kainite-induced neurotoxicity and that cPLA(2) inhibitors can be used to protect hippocampal slices from damage induced by kainate...

..These results suggest that lipid peroxidation observed in the supraventricular corpus callosum at postnatal day 10 could result from an accumulation of iron in this region, at this time...

..Collectively, these might help to elucidate similar molecular mechanisms involved during cell death in neurodegenerative diseases...

..These observations suggest that HNE formation is an early event after this tissue injury, and may contribute to later cell death...

..These results suggest that caution needs to be employed when using cell culture studies to predict effects of L-DOPA and/or dopamine in vivo because of the extracellular generation of reactive species in the culture media...

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..Although MDH was similarly inhibited, the impact was buffered by the high level of this enzyme in kidney mitochondria...

..After a long lag period, therapeutic and other interventions based on a knowledge of redox biology are on the horizon for at least some of the neurodegenerative diseases...

..elegans, but did not affect the dying phase itself, suggesting that it did not act by directly affecting metabolism...

..However, they may be able to help protect the gastro-intestinal tract against reactive oxygen species...

..The results are suggestive of microvascular damage associated with iron accumulation and oxidative stress in the liver during hypercholesterolemia...

..Because glutamate is a major metabolite in the brain, inhibition of GDH by sulfite could contribute to the severe phenotype of sulfite oxidase deficiency in human infants...

..Since this assay is simple, rapid, sensitive and reproducible, it seems suitable to be used as a routine methodology for the measurement of urinary excretion of 8OHdG in large population studies...

..The implications for the putative mitochondrial NOS are discussed...

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..Compound instability and generation of H2O2 must be taken into account in interpreting effects of phenolic compounds on cells in culture...

..068 (-0.009, 0.144)) or urinary or plasma total F(2)-isoprostanes (-0.005 ng/ml (-0.021, 0.010), -0.153 ng/mg (-0.319, 0.014), respectively)...

..By contrast, H(2)O(2) was only responsible for part of the cytotoxicity of the red wines examined. Our data illustrate the danger of extrapolating from cell culture studies to predict the effects of complex beverages in vivo...

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..Hypercholesterolaemia is known to be associated with increased plasma lipid peroxidation which might contribute to such damage...

..Implications for the prospect of successful interventions as well as evidence for and against efficacy of current therapeutic approaches are discussed...

..Taken together, our results suggest that truncation and accumulation of PTEN to the detergent-insoluble membrane fraction are two events associated with the apoptotic signals of the proteasome inhibitor in cortical neurons...

..These results suggest that one action of clofibrate might be to impair mitochondrial function, so stimulating formation of ROS, which eventually contribute to cell death...

..This study highlights the need to use several different assays in the presence of physiologically relevant concentrations of bicarbonate when assessing compounds for peroxynitrite scavenging, in order to avoid misleading results...

..One possibility is that the high content of glutathione is protective to reactive astrocytes. Another possibility is that the high glutathione concentration in reactive astrocytes may be protective to neurons around the glial scar...

..The ability of ascorbate to interact with different cell culture media to produce H2O2 at different rates could account for many or all of the conflicting results obtained using ascorbate in cultured cell assays...

..01). Markers of oxidative damage are altered during the various stages of dengue infection...

..Further studies into those extracts that produced significant lifespan extension indicated that a direct antioxidant effect is unlikely to be the main factor responsible for the modulation of nematode lifespan...

..This study emphasizes the need to examine more than one modified DNA base when assessing the role of reactive species in human disease...

..NO are overproduced, may be cytoprotective against damage caused by HOCl. We propose that this is because HOCl is removed by reacting with NO(2-) to give nitryl chloride (NO2Cl), which is less damaging in our cell system...

..We also discuss the controversial issue of whether and how F2-isoprostane levels in plasma should be standardized against lipids, and, if so, which lipids to use...

..Thus, the culture medium, the cell type and the presence or absence of catalase (e.g. its variable amounts in S9 fractions) must be taken into account in in vitro genotoxicity testing...

..05) significantly decreased at 48 h compared to 0 h after the tomato sauce meal. This study showed that a single dose of tomato sauce meal had only a limited antioxidant effect in vivo...

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..These data add to the growing literature that ROS may sometimes be anti-inflammatory...

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..No significant relationship was observed between urate and vascular outcomes. Depending on its level, serum urate may exhibit protective and deleterious effects on stroke outcomes...

..This review introduces C. elegans as a model organism, discusses aspects that make it attractive for aging and antioxidant research, and addresses some problems and potential artifacts...

..305, p= 0.023) and plasma total HETEs (r= -0.285, p= 0.043). Oxidative damage markers are systemically elevated in PD, which may give clues about the relation of oxidative damage to the onset and progression of PD...

..The role of oxidative damage in the pathogenesis of metabolic syndrome is poorly understood...

..This review summarizes the data we have obtained from in vitro and in vivo (Caenorhabditis elegans) studies examining the diverse effects of traditional medicinal plants and their modes of action...

..The induction of HO-1 protein in response to moderate oxidative stress may explain some of the beneficial pharmacological effects of NF...

..These data suggest that nitryl chloride formed from the reaction of nitrite with HOCl does not contribute to the elevated levels of 3-nitrotyrosine observed in human diseases...

..Our data show, for the first time, that peroxynitrite induces mitochondrial dysfunction in cells via a calcium-dependent process that leads to caspase-independent apoptosis mediated by calpains...

..Ascorbate prevented the loss of gallic acid incubated in DMEM. The role of metal ions and other constituents of the culture medium in promoting H2O2 generation is discussed...

..We also used it to measure levels in various rat tissues of both normal and endotoxin-treated rats, but could not find increased 2'-deoxyinosine formation in tissues even though *NO production was substantially increased...

..Using an improved GC-MS method and pure mtDNA, our analyses revealed that the damage level in mtDNA is not higher, and may be somewhat lower, than that in nDNA...

..For the first time, these results show that HOCl activates the MPT, which leads to the induction of apoptosis and provides a novel insight into the mechanisms of HOCl-mediated cell death at sites of chronic inflammation...

..Our data strengthen the concept that iron contributes to the early stages of the development of atherosclerosis...

..This study is the first to measure the range of aromatic compounds in human fecal water and demonstrates that phenolic acid concentrations are high. The biological effects of phenolics may play an important role in colon function...

..This could explain why hypercholesterolemia is a risk factor for Alzheimer's disease. Further work is necessary to study the mechanism of increased iron transport across the blood brain barrier in atherosclerosis...

..To examine the potential consequences of overproduction of nitric oxide (NO) and nitrite (NO(2) (-)) in the inflamed rheumatoid joint...

..These data suggest that NO(2)(-) may act in an antioxidant manner by removing HOCl at sites of inflammation where both HOCl and z.rad;NO are overproduced...

..We conclude that there is free-radical damage, as evidenced by HNE formation in neurons of the lateral septum after fimbria-fornix transection, and that this increase in HNE is dependent on phospholipase A2 activity...

..Our data illustrate the promise of a "metabolic tuning" intervention strategy, emphasize the importance of mitochondria in nematode aging and highlight operator bias as a potential confounder in lifespan studies...

..Taken together, these results suggest that PEITC potently induces apoptosis and cell cycle arrest in HepG2 cells and that the generation of reactive oxygen species appears to be a secondary effect...

..Our findings suggest that physiological levels of vitamin C provide an important antioxidant defense against HOCl-mediated injury in atherosclerosis...

..We suggest that defects in this pathway at multiple points could produce the common features of neurodegenerative diseases, and that more such defects remain to be discovered...

..Our data indicate that zinc has an antiatherogenic effect, possibly due to a reduction in iron-catalyzed free radical reactions...

..The nitric oxide synthase inhibitor, l-NAME, decreased viability loss and aggregation, suggesting that nitration of proteins may play an important role in aggregation and in the cell death accompanying it...

..We propose that the proteasomal system is a significant target of HNE neurotoxicity in a wide range of neurodegenerative diseases, especially if abnormal proteins are being expressed...

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..The viability loss induced by all the insults showed apoptotic features. The presence of parkin mutations in substantia nigra in Parkinson's disease may increase neuronal vulnerability to a range of toxic insults...

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..Indeed, intracellular ROS were observed to rise sharply on exposure to the conjugates. These results suggest one mechanism by which oxidative stress may occur in the substantia nigra in Parkinson's disease...

..The presence of mutant Parkin in substantia nigra in juvenile parkinsonism may increase oxidative stress and nitric oxide production, sensitizing cells to death induced by other insults...

..The role of gender in predisposition to oxidative damage to DNA needs to be addressed in future studies...

..To study the oxidative DNA damage to adolescents of hepatocellular carcinoma (HCC) families in Guangxi Zhuang Autonomous Region, China...

..Our observations provide evidence for the involvement of reactive species in the inflammatory response after burn. The use of selective iNOS inhibitors may represent a novel approach for the management of human burn injuries...