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)

An intervention study was performed to evaluate the influence of a Mediterranean diet, a high fat diet, and their supplementation with red wine in moderate amounts, on biochemical, physiological, and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months two groups of 21 male volunteers each, received either a Mediterranean diet or a high fat diet; during the second month, red wine was added isocalorically, 240 ml/day. Participants were kept under close medical and nutritional surveillance. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. Plasma vitamin C was significantly decreased in the high fat diet group compared to the Mediterranean diet group. After wine supplementation to the Mediterranean diet, a significant 13.5% increase in plasma vitamin C was observed. Furthermore, when wine was added vitamin E decreased significantly in plasma, 15% in the high fat diet and 26% in the Mediterranean diet. Total plasma antioxidant capacity (total antioxidant reactivity) increased 28% above basal levels in the Mediterranean diet group, but not in the high fat diet group. In both groups, wine induced a marked increase in total antioxidant reactivity above basal levels, 56% and 23%, respectively. Oxidative DNA damage, detected as 8-hydroxydeoxyguanosine (8-OHdG) levels in blood leukocyte DNA, was markedly increased by the high fat diet; however, it was strongly reduced, to approximately 50% basal values, after wine supplementation, both in the high fat diet and Mediterranean diet groups. Endothelial function, evaluated noninvasively as flow-mediated vascular reactivity of the brachial artery, was suppressed by the high fat diet, and was normal after wine supplementation. These effects are attributed to oxidative stress associated with a high fat diet, and to the elevated plasma antioxidant capacity associated with wine consumption and the Mediterranean diet. The results presented support the following conclusions: a high fat diet induces oxidative stress; a diet rich in fruits and vegetables enhances antioxidant defenses; wine supplementation to a high fat or a Mediterranean diet increases plasma antioxidant capacity, decreases oxidative DNA damage, and normalizes endothelial function.
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PMID:Plasma polyphenols and antioxidants, oxidative DNA damage and endothelial function in a diet and wine intervention study in humans. 1037 Aug 76

The chemopreventive effects of antioxidants (vitamin E, beta-carotene, vitamin C and red ginseng) on oxidative DNA and protein (globin) damages were comparatively investigated in the peripheral blood of smokers (> or = 20 cigarettes/day). Smokers showed a lower baseline level of plasma micronutrients (vitamin C and beta-carotene) (P < 0.01) and higher baseline level of oxidative DNA or protein damage than non-smokers (N = 5; P < 0.05). During daily supplementation of antioxidants (200 IU vitamin of E, 9 mg of beta-carotene, 500 mg of vitamin C, or 1.8 g of red ginseng) for 4 weeks, smokers plasma antioxidant concentrations increased linearly, while their mean levels of 8-hydroxydeoxyguanosine (8-OHdG) and carbonyl contents decreased compared with those in smokers supplemented with a placebo (P < 0.05). Levels of urinary and plasma cotinine remained steady in smokers regardless of supplementation with antioxidants. 8-OHdG and carbonyl content decreased in a time-dependent manner (as the total intake dose increased) after supplementation with vitamin E (8-OHdG, 33.8%; carbonyl content, 43.6%) or red ginseng (8-OHdG, 31.7%; carbonyl content, 21.3%). These preliminary data suggest that supplementation with antioxidants might protect smokers from oxidative damages and could reduce cancer risk or other diseases caused by free radicals associated with smoking.
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PMID:Inhibition of oxidative DNA damage, 8-OHdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, beta-carotene and red ginseng). 1039 77

The interaction of chelators and reducing agents is of particular importance in understanding iron-associated pathology since catalytic iron undergoes cyclic reduction and oxidation in vivo. Therefore, we treated plasmid DNA with free or chelated Fe(III) in the presence of biological reductants, and simultaneously measured the number of single strand breaks (SSBs) and oxidative base modification (8-hydroxy-2'-deoxyguanosine; 8-OHdG) by quantitative gel electrophoresis and HPLC with electrochemical detection, respectively. Production of SSBs and 8-OHdG was linearly correlated suggesting that these two different lesions share a common chemical mechanism. The levels of both lesions were enhanced when Fe(III) was chelated to citrate or nitrilotriacetic acid. Reducing agents showed different potency in inducing DNA damage catalyzed by chelated iron (L-ascorbate > L-cysteine > H2O2). Chelation increased SSB formation by approximately 8-fold and 8-OHdG production by approximately 4-fold. The ratio of SSB/8-OHdG catalyzed by chelated iron, which is twice as high as by unchelated iron, indicates that chelation affects iron-catalyzed oxidative DNA damage in a specific way favoring strand breakage over base modification. Since iron is mostly chelated in biological systems, the production of genomic and mitochondrial DNA damage, particularly strand breaks, in diseases involving iron overload is likely to be higher than previously predicted from studies using unchelated iron.
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PMID:Iron chelators modulate the production of DNA strand breaks and 8-hydroxy-2'-deoxyguanosine. 1049 Feb 41

Interaction of Cr(VI) and ascorbate in vitro generates Cr(V), Cr(IV), Cr(III), carbon-based alkyl radicals, COO(*)(-), (*)OH, and ascorbate radicals and induces DNA interstrand cross-links at guanines. To determine which specific Cr species and free radicals cause DNA damage, we investigated the effects of mannitol and catalase on the formation of reactive intermediates, Cr-DNA associations, DNA polymerase-stop sites, and 8-hydroxydeoxyguanosine (8-OHdG) adducts induced by Cr(VI)/ascorbate in a Hepes buffer. EPR spectra showed that mannitol trapped reactive Cr(V), forming a stable Cr(V)-diol complex, and inhibited the radicals induced by Cr(VI)/ascorbate, whereas catalase or heat-denatured catalase enhanced the levels of Cr(V) without altering the radical signals. Mannitol markedly inhibited the retarded gel electrophoretic mobility of supercoiled plasmids and the formation of DNA polymerase-stop sites induced by Cr(VI)/ascorbate, but catalase did not. On the other hand, mannitol reduced only 32% of the Cr-DNA adducts induced by Cr(VI)/ascorbate, suggesting that Cr monoadducts (possibly DNA-Cr-mannitol adducts) are the major lesions generated in the Cr(VI)/ascorbate/mannitol/DNA solution. Native catalase but not heat-denatured catalase protected approximately 25% of the Cr-DNA adducts induced by Cr(VI)/ascorbate, suggesting that hydrogen peroxide may be involved. Mannitol could not completely inhibit the formation of 8-OHdG adducts induced by Cr(VI)/ascorbate, indicating that this DNA damage may be generated before the action of mannitol to trap Cr(V) and reactive oxygen species. Alternatively, Cr-peroxide intermediates may also lead to 8-OHdG formation to account for the incomplete prevention by mannitol. Catalase or heat-denatured catalase partially protected the formation of 8-OHdG adducts induced by Cr(VI)/ascorbate, suggesting an effect of proteins. Together, the results from this study suggest that the primary species generated during the reduction of Cr(VI) by ascorbate are hydroxyl radicals and Cr(V) species, responsible for the formation of 8-OHdG and DNA cross-links, respectively.
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PMID:Effects of mannitol or catalase on the generation of reactive oxygen species leading to DNA damage by Chromium(VI) reduction with ascorbate. 1052 78

Increased oxidative stress has been associated with work at high altitude; however, it is not known whether oxidative stress is a significant problem at moderate altitudes. The oxidative stress indicators, breath pentane (BP), 8-hydroxydeoxyguanosine (8-OHdG), oxygen radical absorption capacity (ORAC), 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and lipid peroxides (LPO) were measured in breath, blood and urine samples of U.S. Marines engaged in moderate altitude ( approximately 3000 m) cold weather field training. The test subjects were divided into a placebo and four antioxidant supplement groups (n = 15/group) and received the following supplements for 28 d: 1) vitamin E, 440 alpha-tocopherol equivalents (alpha-TE); 2) vitamin A, 2000 retinol equivalents (RE) of beta-carotene; 3) vitamin C, 500 mg ascorbic acid; 4) a mixture of 440 alpha-TE, 2000 RE of beta-carotene, 500 mg ascorbic acid, 100 microg selenium and 30 mg zinc daily. Strenuous work ( approximately 23 MJ/d) in cold weather at moderate altitude was accompanied by increases in several indicators of oxidative stress that were not effectively controlled by conventional antioxidant supplements. The group receiving the antioxidant mixture exhibited lower BP (P < 0. 05) compared with those receiving single antioxidant supplements; however, not all markers of oxidative stress responded like BP. Because these markers did not respond in the same manner, it is important to include markers from more than one source to assess the effect of supplemental dietary antioxidants.
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PMID:Oxidative stress in humans during work at moderate altitude. 1053 77

Phosphine (PH(3)), from hydrolysis of aluminum, magnesium and zinc phosphide, is an insecticide and rodenticide. Earlier observations on PH(3)-poisoned insects, mammals and a mammalian cell line led to the proposed involvement of oxidative damage in the toxic mechanism. This investigation focused on PH(3)-induced oxidative damage in rats and antioxidants as candidate protective agents. Male Wistar rats were treated ip with PH(3) at 2 mg/kg. Thirty min later the brain, liver, and lung were analyzed for glutathione (GSH) levels and lipid peroxidation (as malondialdehyde and 4-hydroxyalkenals) and brain and lung for 8-hydroxydeoxyguanosine (8-OH-dGuo) in DNA. PH(3) caused a significant decrease in GSH concentration and elevation in lipid peroxidation in brain (36-42%), lung (32-38%) and liver (19-25%) and significant increase of 8-OH-dGuo in DNA of brain (70%) and liver (39%). Antioxidants administered ip 30 min before PH(3) were melatonin, vitamin C, and beta-carotene at 10, 30, and 6 mg/kg, respectively. The PH(3)-induced changes were significantly or completely blocked by melatonin while vitamin C and beta-carotene were less effective or inactive. These findings establish that PH(3) induces and melatonin protects against oxidative damage in the brain, lung and liver of rats and suggest the involvement of reactive oxygen species in the genotoxicity of PH(3).
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PMID:Phosphine-induced oxidative damage in rats: attenuation by melatonin. 1071 45

Chromium compounds are well documented carcinogens. Cr(III) is more reactive than Cr(VI) toward DNA under in vitro conditions. In the present study, we investigated the ability of Cr(III) to induce oxidative DNA damage by examining the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in calf thymus DNA incubated with CrCl(3) plus H(2)O(2). We measured 8-OH-dG using HPLC with electrochemical detection. In the presence of H(2)O(2), we observed that Cr(III)-induced formation of 8-OH-dG in isolated DNA was dose and time dependent. Melatonin, ascorbate, and vitamin E (Trolox), all of which are free radical scavengers, markedly inhibited the formation of 8-OH-dG in a concentration-dependent manner. The concentration that reduced DNA damage by 50% was 0.51, 30.4, and 36.2 microM for melatonin, ascorbate, and Trolox, respectively. The results show that melatonin is 60- and 70-fold more effective than ascorbate or vitamin E, respectively, in reducing oxidative DNA damage in this in vitro model. These findings also are consistent with the conclusion that the carcinogenic mechanism of Cr(III) is possibly due to Cr(III)-mediated Fenton-type reactions and that melatonin's highly protective effects against Cr(III) relate, at least in part, to its direct hydroxyl radical scavenging ability.
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PMID:Chromium(III)-induced 8-hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E. 1144 22

Oxidative DNA damage may be important in mutagenic, carcinogenic, and aging processes. Although it is plausible that antioxidant vitamins may reduce oxidative DNA damage, evidence from human studies has been sparse and inconsistent. We determined the short-term effects of vitamin C (500 mg/day) and vitamin E (400 IU d-alpha-tocopheryl acetate/day) supplements on oxidative DNA damage in a double-masked, placebo-controlled, 2x2 factorial trial in 184 nonsmoking adults. Mean duration of supplementation was 2 months. Oxidative DNA damage was measured by 24-h urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG). At baseline, urinary 8-OHdG (mean +/- SE; ng/mg creatinine) was associated with race (15.6 +/- 0.8 in African Americans versus 20.3 +/- 1.2 in Caucasians, P = 0.001), prior antioxidant supplement use (18.6 +/- 0.8 in users versus 13.8 +/- 1.5 in non-users, P = 0.007), and regular exercise (19.2 +/- 1.1 in exercisers versus 16.6 +/- 0.9 in non-exercisers, P = 0.04). Fruit and vegetable intake and serum ascorbic acid were inversely associated with urinary 8-OHdG (P-trend = 0.02 and 0.016, respectively). The benefits of fruit and vegetable intake became evident with the consumption being at least three servings/day. At the end of supplementation, change from baseline in urinary 8-OHdG (mean +/- SE; ng/mg creatinine) was -0.6 +/- 1.4 (P = 0.61), 0.6 +/- 1.1 (P = 0.59), 0.5 +/- 1.0 (P = 0.61), and 1.6 +/- 1.4 (P = 0.27) in the placebo, vitamin C alone, vitamin E alone, and combined vitamins C and E groups, respectively. In overall and subgroup analyses, there was no significant main effect or interaction effect of the supplements on urinary 8-OHdG. In conclusion, supplementation of diet with vitamin C (500 mg/day) and vitamin E (400 IU d-alpha-tocopheryl acetate/day) had no significant main effect or interaction effect on oxidative DNA damage as measured by urinary 8-OHdG in nonsmoking adults. However, several aspects of a healthy lifestyle were associated with lower oxidative DNA damage.
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PMID:The effects of vitamin C and vitamin E on oxidative DNA damage: results from a randomized controlled trial. 1091 32

In contrast to proteins and lipids, oxidative damage to DNA has not been well studied in patients undergoing hemodialysis (HD). We hypothesized that phagocytes are activated after blood-membrane contact during HD, and oxidants from metabolic activation can damage leukocyte DNA. To test this hypothesis, the 8-hydroxy-2'-deoxyguanosine (8-OHdG) content of leukocyte DNA was measured by high-performance liquid chromatography electrochemical detection method in 35 age- and sex-matched healthy subjects, 22 undialyzed patients with advanced renal failure, and 109 HD patients to assess the relation between oxidative DNA damage and complement-activating membranes, blood antioxidants, and iron status. Dialysis membranes were classified into complement-activating (cellulose; n = 55) and non-complement-activating (polymethylmethacrylate [PMMA]; n = 35; polysulfone [PS]; n = 19) membranes. We found increased oxidative stress in undialyzed and HD patients based on a decrease in plasma levels of ascorbate and alpha-tocopherol adjusted for blood lipid (alpha-tocopherol/lipid), serum albumin, and reduced glutathione levels in whole blood and an increase in oxidized glutathione levels in whole blood compared with controls (P < 0.001). The greatest 8-OHdG level in leukocyte DNA was in HD patients, followed by undialyzed patients and healthy controls (P < 0.001), and was significantly greater in HD patients using cellulose membranes than those using PMMA or PS membranes (P < 0.001). 8-OHdG levels correlated with plasma alpha-tocopherol/lipid (r = -0.314; P < 0.005), serum iron (r = 0. 446; P < 0.001), and transferrin saturation values (r = 0.202; P < 0.05) in the analysis of all HD patients. In a 6-week crossover study, 8-OHdG levels significantly decreased after the switch from cellulose to synthetic membranes for 2 weeks and increased after the shift from synthetic to cellulose membranes (P < 0.05). Iron metabolism indices and plasma alpha-tocopherol/lipid values did not change significantly in the study period. We conclude that 8-OHdG content in leukocyte DNA is a biomarker of oxidant-induced DNA damage in HD patients. Oxidative DNA damage is a consequence of uremia, further augmented by complement-activating membranes.
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PMID:8-hydroxy-2'-deoxyguanosine of leukocyte DNA as a marker of oxidative stress in chronic hemodialysis patients. 1105 49

Free radicals derived from the reaction of iron and oxygen are thought to be one of the causes of tissue injury. In order to identify whether oxygen concentrations are an important factor in iron-mediated damage to cells, cytotoxic effects of Fe(3+)-NTA on human fibroblasts (KMST-6 line) were studied under the conditions of 1% and 20% oxygen concentrations in an incubator. A comparison of the effects of Fe(3+)-NTA on cells cultured in 1% and 20% oxygen environments showed that the following features were more prominent under the usual culture concentrations of 20% oxygen: i) cytotoxicity, ii) increase in intracellular reactive oxygen species, iii) increase in H(2)O(2) production in the cells, and iv) formation of 8-hydroxydeoxyguanosine. To elucidate the roles of endogenous antioxidants, the levels of manganese superoxide dismutase (MnSOD) and catalase were measured by Western blotting. The increase in MnSOD in the presence of Fe(3+)-NTA was greater under the condition of 20% O(2) than under the condition of 1% O(2). The expression of catalase was significantly up-regulated at 20% O(2). However, when the cells were treated with Fe(3+)-NTA, the expression of catalase was markedly down-regulated under the condition of 20% O(2). Hydroxyl radical scavengers such as vitamin E, dimethyl-sulfoxide (DMSO) and mannitol reduced endogenous ROS generation and alleviated the cytotoxic effects of iron. On the other hand, superoxide dismutase (SOD), vitamin C and catalase did not show any protective effects against Fe(3+)-NTA. These findings suggest that enhanced cytotoxic effects of Fe(3+)-NTA at 20% O(2 )are due to endogenously produced hydroxyl radicals.
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PMID:Effects of oxygen concentrations on human fibroblasts treated with Fe(3+)-NTA. 1117 10


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