Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species and reactive nitrogen species are formed in the human body. Endogenous antioxidant defences are inadequate to scavenge them completely, so that ongoing oxidative damage to DNA, lipids, proteins and other molecules can be demonstrated and may contribute to the development of cancer, cardiovascular disease and possibly neurodegenerative disease. Hence diet-derived antioxidants may be particularly important in protecting against these diseases. Some antioxidants (e.g. ascorbate, certain flavonoids) can exert pro-oxidant actions in vitro, often by interaction with transition metal ions. The physiological relevance of these effects is uncertain, as is the optimal intake of most diet-derived antioxidants. In principle, these questions could be addressed by examining the effects of dietary composition and/or antioxidant supplementation upon parameters of oxidative damage in vivo. The methods available for measuring steady-state damage (i.e. the balance between damage and repair or replacement of damaged molecules) and the actual rate of damage to DNA, proteins and lipids are reviewed, highlighting areas in which further methodological development is urgently required.
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PMID:Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans. 881 44

The increasing incidence of non-Hodgkin's lymphoma (NHL) in the United States is only partially explained by known risk factors. Nitrate is a contaminant of drinking water in many rural areas. We evaluated its association with NHL after accounting for dietary nitrate intake. For 156 cases and 527 controls who used Nebraska community supplies, average nitrate exposure was estimated from 1947 through 1979. Longterm consumption of community water with average nitrate levels in the highest quartile (> or = 4 mg per liter nitrate-nitrogen) was positively associated with risk [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.1-3.6]. Dietary nitrate, which came mainly from vegetables, was not associated with NHL risk, after adjusting for vitamin C and carotene intakes. Persons with a lower intake of vitamin C were at slightly higher risk of developing NHL than persons whose daily intake was > or = 130 mg, for all levels of intake of drinking water nitrate; our findings were similar for the combined effect of water nitrate and carotene intake. Nitrate levels in private wells were measured at the time of the interview for 51 cases and 150 controls but were not associated with the risk of NHL after adjusting for pesticide use on the farm. These findings indicate that longterm exposure to elevated nitrate levels in drinking water may contribute to the risk of NHL.
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PMID:Drinking water nitrate and the risk of non-Hodgkin's lymphoma. 886 75

A gas-phase oxygen biosensor based on blue copper-containing oxidases was developed. Blue-oxidase enzymes, including laccase and ascorbate oxidase, have a blue chromophore prosthetic group, type 1 Cu+2, which can be reduced and decolorized with reducing substrates. When the enzyme is reoxidized with molecular oxygen, there is a concomitant return of the blue color. The oxygen biosensor consisted of the Rhus vernicifera laccase and ascorbate as substrate enclosed in pouches of low-density polyethylene under nitrogen gas. Operational stability of the biosensor was established by exposing it to different oxygen/nitrogen gas mixtures at 5 degrees C. Gas-phase oxygen concentrations were measured by keeping it under nitrogen gas and subsequently recording the rate of reappearance of the enzyme blue color, both visually and spectrophotometrically at 610 nm. The oxygen biosensor was able to detect a wide range of oxygen concentrations. The time required to recover the blue color, namely the biosensor response time, at the optimized assay conditions of 5 degrees C and a high-water activity level, was determined. This research describes the development of an oxygen biosensor with adequate activity and stability to measure gas-phase oxygen concentrations at 5 degrees C and high-water activity levels. The oxygen biosensor could be used to indicate oxygen concentrations above acceptable levels in headspace oxygen concentration which could affect the quality and safety of products packaged under initial low levels of oxygen concentration.
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PMID:Development of a gas-phase oxygen biosensor using a blue copper-containing oxidase. 888 2

Peroxynitrite, formed by reaction of superoxide and nitric oxide, appears to be an important tissue-damaging species generated at sites of inflammation. In this paper, we compare the abilities of several biological antioxidants to protect against peroxynitrite-dependent inactivation of alpha 1-antiproteinase, and to inhibit tyrosine nitration upon addition of peroxynitrite. GSH and ascorbate protected efficiently in both systems. Uric acid inhibited tyrosine nitration but not alpha 1-antiproteinase inactivation. The possibility that ascorbic acid is an important scavenger of reactive nitrogen species in vivo is discussed.
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PMID:Protection against peroxynitrite-dependent tyrosine nitration and alpha 1-antiproteinase inactivation by ascorbic acid. A comparison with other biological antioxidants. 888 93

A rapid method is described for isolation and concentration of plasma low density lipoproteins (LDL) using a Beckman L80 ultracentrifuge equipped with a 70.1 Ti fixed angle rotor. The isolation of LDL achieved by a discontinuous gradient density step (180 min) was followed by a simultaneous purification and concentration step (45 min) using ultrafiltration through a collodium bag under nitrogen. This dialysis/concentration step, in contrast to the standard dialysis techniques in batch or by filtration through short gel columns, prevents oxidation and dilution of the sample. Electrophoresis in agarose and sodium dodecylsulfate-polyacrylamide (SDS-PAGE) gels were used to monitor LDL surface charge, purity, and contamination with plasma proteins. The artifactual oxidation of LDL during isolation and subsequent handling, and thus the ability of LDL preparation for oxidation/antioxidation studies, was assessed by the determination of endogenous hydroperoxides and thiobarbituric acid reactive substances. The dialysis/concentration step by ultrafiltration that allows the obtention of a concentrated and purified LDL preparation was validated by the absence of ascorbate and urate, as measured by HPLC. This method led to LDL preparations free of water-soluble plasma antioxidants that were minimally oxidized and suitable for reliable in vitro LDL oxidation and inhibition studies. The applicability of this methodology was tested by studying the alpha-tocopherol content of LDL in a Portuguese population of university students.
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PMID:Rapid isolation of low density lipoproteins in a concentrated fraction free from water-soluble plasma antioxidants. 901 22

We explored the effects of congeners of nitrogen monoxide (NO) on cultured mesencephalic neurons. Sodium nitroprusside (SNP) was used as a donor of NO, the congeners of which have been found to exert either neurotoxic or neuroprotective effects depending on the surrounding redox milieu. In contrast to a previous report that suggests that the nitrosonium ion (NO+) is neuroprotective to cultured cortical neurons, we found that the nitrosonium ion reduces the survival of cultured dopamine neurons to 32% of control. There was a trend for further impairment of dopamine neuron survival, to only 7% of untreated control, when the cultures were treated with SNP plus ascorbate, i.e. when the nitric oxide radical (NO.) had presumably been formed. We also evaluated the effects of an inhibitor of lipid peroxidation, the lazaroid U-83836E, against SNP toxicity. U-83836E exerted marked neuroprotective effects in both insult models. More than twice as many dopamine neurons (75% of control) survived when the lazaroid was added to SNP-treated cultures and the survival was increased eight-fold (to 55% of control) when U-83836E was added to cultures treated with SNP plus ascorbate. We conclude that the congeners of NO released by SNP are toxic to mesencephalic neurons in vitro and that the lazaroid U-83836E significantly increases the survival of dopamine neurons in situations where congeners of NO are generated.
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PMID:Mesencephalic neuron death induced by congeners of nitrogen monoxide is prevented by the lazaroid U-83836E. 902 82

Exposure of human blood plasma to peroxynitrite in the presence of 3,5-dibromo-4-nitrosobenzenesulphonic acid (DBNBS) resulted in the trapping of a strongly immobilized nitroxide radical adduct. The adduct was due to protein-centred radicals derived not only from serum albumin but also from other major plasma proteins (fibrinogen, IgG, alpha1-antitrypsin and transferrin). Urate significantly protected plasma from the peroxynitrite-induced DBNBS-plasma protein adduct, whereas ascorbate and glutathione were protective at concentrations exceeding those usually found in plasma. Alkylation of plasma -SH groups did not affect the intensity of DBNBS-plasma protein adduct, whereas bicarbonate increased its formation, thus showing a pro-oxidant effect. The DBNBS-plasma protein adduct provided little structural information, but subsequent non-specific-protease treatment resulted in the detection of an isotropic three-line spectrum, indicating the trapping of radicals centred on a tertiary carbon. The nitrogen hyperfine coupling constant of this adduct and its superhyperfine structure were similar to those of DBNBS-tryptophan peptides with the alpha-amino group of tryptophan linked in the amide bond, consistent with a radical adduct formed at C-3 of the indole ring of tryptophan-containing peptides. DBNBS was unable to trap radicals derived from peroxynitrite-treated tyrosine or tyrosine-containing peptides. Methionine treated with peroxynitrite resulted in the trapping of at least two DBNBS-methionine adducts with hyperfine structures different from that of protease-treated DBNBS-plasma proteins. These results demonstrate that peroxynitrite induced in blood plasma the formation of protein radicals centred on tryptophan residues and underline the relevance of the one-electron oxidation pathway of peroxynitrite decomposition in biological fluids.
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PMID:One-electron oxidation pathway of peroxynitrite decomposition in human blood plasma: evidence for the formation of protein tryptophan-centred radicals. 903 62

The recent finding that dendritic spines (on which 90% of all excitatory synapses on pyramidal cells are formed) are not permanent structures but are continually being formed and adsorbed has implications for the present theoretical basis of neurocomputation, which is largely based on the concept of fixed nerve nets. This evidence would tend to support the recent theories of Edelman, Freeman, Globus, Pribram and others that neuronal networks in the brain operate mainly as nonlinear dynamic, chaotic systems. This paper presents a hypothesis of a possible neurochemical mechanism underlying this synaptic plasticity based on reactive oxygen species and toxic 0-semiquinones derived from catecholamines (i) by the enzyme prostaglandin H synthetase induced by glutamatergic NMDA receptor activation and (ii) by reactive nitrogen species derived from nitric oxide in a low ascorbate environment. A key factor in this neuromodulation may be the fact that catecholamines are potent antioxidants and free radical scavengers and are thus able to affect the redox mediated balance at the glutamate receptors between synapse formation and synapse removal that may be a key factor in neurocomputational plasticity. But catecholamines are also easily oxidized to neurotoxic 0-semiquinones and this may be relevant to the pathology of several diseases including schizophrenia. The relationship between dopamine release and positive reinforcement is relevant to this hypothesis.
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PMID:The biochemical basis of synaptic plasticity and neurocomputation: a new theory. 914 26

Traffic and cooking and heating using unventilated gas appliances are the major sources for environmental exposures to nitrogen oxides. The nitrogen oxides of importance for health effects are nitrogen dioxide (NO2), and maybe the two derivatives nitric and nitrous acid (HNO3 and HNO2). Due to this, human exposure studies on NO2 have been performed intensively during the last decades. Nitric oxide (NO) is quantitatively the major pollutant, but is not very toxic and may even be used in treatment of certain conditions of respiratory insufficience. Major lung function effects shown in humans are a decrease in the forced expiratory volume in the first second (FEV1), increased specific airway resistance (SRaw), and increased responsiveness in bronchial provocation tests. Studies have been performed primarily on healthy and asthmatic subjects, but only asthmatic subjects show these reactions at levels relevant to exposures found in indoor and outdoor environments. Other effects found in animal studies and epidemiological studies like decreased mucociliary function, increased susceptibility to infections have not been proven in humans and are therefore still on debate. Human studies have furthermore shown that antioxidants like vitamin C and E may prevent effects of NO2, which is explained by that the mechanism of NO2-action is the oxidation of airway phospholipids. A large inconsistency in the results of the studies makes it very difficult to conclude about dose-response relationships and about no observed effect levels (NOEL). Single study observations and results of meta-analyses have indicated a biphasic dose-response relationship. However, such a relationship is hard to explain and need to be investigated further. Several other explanations, e.g. the limited statistical power of the studies, may exist and will be discussed.
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PMID:Clinical studies of effects of nitrogen oxides in healthy and asthmatic subjects. 916 53

Reactive oxygen and nitrogen species play an important role in many human diseases including cancer. We have found that incubation of pBR322 plasmid DNA with a nitric oxide (NO)-releasing compound such as diethylamine NONOate and a polyhydroxyaromatic compound such as catechol, 1,4-hydroquinone, or pyrogallol caused synergistic induction of single-strand breakage, whereas either compound alone induced much less breakage. Phenol, resorcinol, or guaiacol (O-methylcatechol) did not exhibit this synergistic effect of DNA damage with NO. The strand breakage induced by NO with pyrogallol was prevented by excess superoxide dismutase, carboxy-PTIO (an NO-trapping agent), or anti-oxidants (urate, ascorbate). Possible mechanisms for the induction of this synergistic effect of NO and polyhydroxyaromatic compounds on the strand breakage are proposed, including involvement of peroxynitrite formed from NO and O2.- derived from autooxidation of polyhydroxyaromatics. This pathway for generation of reactive species from NO and catechol-type compounds (e.g., L-dopa, catechol-estrogen) may be important in many pathological conditions, because both compounds are concurrently formed or present in vivo. On the other hand, NO dose-dependently inhibited the strand breakage mediated by 1,4-hydroquinone plus Cu2+ or Fenton reaction (H2O2, iron or copper). This inhibition could be due to formation of a complex between NO and a metal ion, inhibiting generation of reactive species from H2O2. Our results can account for contrasting activities of NO reported in relation to tissue injury. NO can play both detrimental and beneficial roles in DNA damage, depending on the type and amounts of reactive oxygen species and metal ions concurrently present.
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PMID:Nitric oxide synergistically enhances DNA strand breakage induced by polyhydroxyaromatic compounds, but inhibits that induced by the Fenton reaction. 918 9


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