DrugBank:EXPT00568 - FACTA Search

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Query: DrugBank:EXPT00568 (ascorbate)
23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the influence of docosahexaenoic acid (DHA) supplementation on oxidative DNA damage in bone marrow between young and aged rats. As a marker of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG) in DNA was analyzed. Young (5-week-old) and aged (100-week-old) female Wistar rats were given DHA (300mg/kg body weight/day) or vehicle (control) orally for 12 weeks. The 8-OHdG in the bone marrow in the aged DHA group was significantly higher than that in the other groups. Vitamin E concentrations, however, did not differ among the groups regardless of the DHA supplementation. Vitamin C (ascorbic acid) concentrations in the aged control group were approximately 1/2 those in the young control group. The concentrations of vitamin C tended to be higher in the young DHA group and lower in the aged DHA group when compared to their respective control groups. Changes in the concentrations of vitamin C and vitamin E in plasma were similar to those in the bone marrow. The activity of hepatic l-gulono- gamma -lactone oxidase, an enzyme responsible for vitamin C synthesis, corresponded well to the concentrations of vitamin C in the bone marrow and the plasma. These results suggest that in aged rats, but not young rats, excess supplementation of DHA induces oxidative DNA damage in bone marrow and that the decrease in vitamin C synthesis in aged rats is involved in the mechanisms of DNA damage.
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PMID:Docosahexaenoic acid supplementation-increased oxidative damage in bone marrow DNA in aged rats and its relation to antioxidant vitamins. 1132 78

1. The present study was undertaken to determine whether endothelial function or morphology was altered in aortic rings of rats after irradiation, to investigate the mechanism of radiation effects on the endothelium and to examine the effect of vitamin C treatment against radiation-induced damage of the endothelium. 2. Female Sprague-Dawley rats were randomized into four groups (control, radiation, radiation + vitamin C, radiation + vitamin C + NG-nitro-L-arginine methyl ester (L-NAME); n = 10 for each group and n = 7 for the control group) and were irradiated with 10 Gy of 137Cs as a radiation source. Segments of the thoracic aorta were obtained and isometric tension, levels of 8-hydroxydeoxyguanosine (OH-dG) and immunohistochemical staining were measured. 3. Irradiation significantly impaired the acetylcholine-induced vasodilation of aortic segments, an effect that could be prevented by pretreatment with vitamin C (500 mg/kg per day). This beneficial effect of vitamin C was abolished by the addition of L-NAME (100 microg/kg per day), an inhibitor of nitric oxide (NO) synthesis. Irradiation significantly increased the level of OH-dG in the aorta (1.02 +/- 0.27 vs 2.61 +/- 0.78 OH-dG/105 deoxyguanosine (dG) for control and irradiated tissues, respectively; P < 0.01), an increase that was prevented by vitamin C treatment (1.59 +/- 0.23 OH-dG/105 dG; P < 0.01). Irradiation caused significant de-endothelialization (von Willebrand factor (vWF) staining was 93 +/- 7 vs 100% in irradiated and control tissues, respectively; P < 0.05) and this was prevented by vitamin C treatment (vWF staining 98 +/- 3%; P < 0.05). 4. Radiation caused endothelial damage and impaired NO production through oxidative injury, resulting in a selective impairment of endothelial-dependent vasodilation that could be prevented by vitamin C, partly through anti-oxidant mechanisms.
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PMID:Vitamin C prevents radiation-induced endothelium-dependent vasomotor dysfunction and de-endothelialization by inhibiting oxidative damage in the rat. 1155 21

Antitumor agents are used as a common therapy against some kinds of cancer. However, as with many agents that have mammalian cell toxicity as a target, physiological adverse effects can occur such as nephrotoxicity and genotoxicity that can be induced in non-tumor cells by generating activated oxygen species, which attack the DNA frequently resulting in oxidative DNA damage. To diminish the undesirable side-effects of therapy and to reduce the levels of oxidative DNA damage, it is recommended for patients to ingest food supplements and vitamins combinations containing substantial amounts of antioxidants. In the present study, we investigated the effects of cisplatin and vitamin C on the renal toxicity and on the oxidative DNA damage. Rats were co-treated with the chemotherapeutic agent cisplatin (5 mg kg(-1) body weight) and dietary doses of vitamin C (50 and 100 mg kg(-1) body weight). Results demonstrated that depending on the treatment protocol, we observed alterations in parameters such as body weight, urinary volume and urinary creatinine, indicating some kidney toxicity. We also observed changes in the urinary levels of 8-OHdG, suggesting possible oxidative DNA damage.
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PMID:Effect of vitamin C supplementation against cisplatin-induced toxicity and oxidative DNA damage in rats. 1159 67

We examined time-dependent changes in antioxidant vitamins and oxidative damage to DNA and lipids in the bone marrow, liver, and plasma of rats given total body irradiation (TBI) with X-rays at 3 Gy. The oxidative damage to DNA and lipids was evaluated by measuring increases of 8-hydroxydeoxyguanosine (8OHdG) in DNA and 4-hydroxy-2-nonenal (HNE), respectively. After the TBI, marked increases in 8OHdG and HNE were detected at 3 to 5 h in the bone marrow, while gradual increases in these parameters were detected after a few days in the liver. These changes in 8OHdG and HNE were well correlated within each tissue. In the bone marrow, levels of both vitamin C and vitamin E were decreased by the TBI; however, the changes in vitamin C were earlier and greater than those in vitamin E. In the liver, the level of vitamin C did not decrease, but that of vitamin E decreased due to the TBI. Changes in HNE, vitamin C, and vitamin E in the plasma were similar to those in the liver. Within each tissue, the time of decrease in antioxidants was almost the same as that of the increase in oxidative damage. An increase in total iron due to the TBI was also detected in these tissues. In particular, the total iron in the bone marrow was markedly increased at a few hours after the TBI, with a slight increase in transferrin and no increase in ferritin. Exposure studies performed on cells or isolated DNA showed that an increase in 8OHdG was detected immediately after irradiation at more than 100 Gy in bone marrow cells and at less than 10 Gy in isolated DNA, suggesting that an increase in 8OHdG is undetectable even in bone marrow immediately after the TBI at 3 Gy. These results indicate that the onset of oxidative damage to DNA and lipids was delayed after TBI at 3 Gy, that it was quite different in the bone marrow and the liver, and that an increase in iron and decrease in antioxidant vitamins were involved in the mechanism of oxidative damage.
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PMID:Different onsets of oxidative damage to DNA and lipids in bone marrow and liver in rats given total body irradiation. 1167 39

This study focuses on the extent of oxidative DNA damage in peripheral blood leukocytes of chronic peritoneal dialysis (CPD) patients. 8-Hydroxy 2'-deoxyguanosine (8-OHdG) contents in peripheral leukocyte DNA were measured by an HPLC-electrochemical detection method in 24 age- and sex-matched healthy subjects, 22 nondialyzed patients with advanced renal failure, and 42 CPD patients. Mean 8-OHdG content was the highest in CPD patients, followed by the nondialyzed patients, and then by the healthy subjects (19.4 versus 11.9 versus 8.3/10(6) dG; ANOVA P < 0.001). In nondialyzed subjects, peripheral leukocyte 8-OHdG contents inversely correlated with renal creatinine clearance (r = -0.772; P < 0.001). Deficiency of blood antioxidants in CPD and nondialyzed patients was expressed by the lower plasma levels of ascorbate, cholesterol-standardized alpha-tocopherol and whole-blood reduced glutathione, and the higher levels of whole-blood oxidized glutathione as compared with healthy subjects (ANOVA P < 0.05). Mean serum ferritin and iron levels and transferrin saturation were higher in the CPD patients than those in the nondialyzed patients and controls (ANOVA P < 0.05). Flow cytometric analyses of intracellular reactive oxygen species production of peripheral leukocytes showed that spontaneous production by granulocytes, as well as phorbol-12-myristate-13-acetate (PMA)-induced production by granulocytes, lymphocytes and monocytes, were the highest from CPD patients, followed by nondialyzed patients, and then by the healthy subjects (ANOVA P < 0.05). Forward stepwise multiple regression disclosed that uremia, PD treatment, spontaneous and PMA-induced reactive oxygen species production in leukocytes, and serum iron were the independent determinants of peripheral leukocyte 8-OHdG content (R(2) = 0.769; P < 0.001). In conclusion, profound increased 8-OHdG levels in peripheral leukocyte DNA occur in the course of chronic renal failure, gradually increase with its progression, and are further exacerbated by PD treatment.
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PMID:Increased oxidative damage to peripheral blood leukocyte DNA in chronic peritoneal dialysis patients. 1196 Oct 20

We examined the effects of dietary vitamin E (VE) on oxidative damage to DNA and lipids in the liver a few days after total body irradiation (TBI). ODS rats, which lack vitamin C synthesis, were fed either a low VE diet (4.3 mg VE/kg) or a basal VE diet (75.6 mg VE/kg) for 5 weeks while vitamin C was supplied in the drinking water. The VE level in the liver of the low VE group was lower and the levels of lipid peroxides were higher compared to those of the basal VE group: the relative levels in the two groups were 1:30 for VE, 18:1 for 4-hydroxynonenal (HNE), and 10:1 for hexanal (HA). The level of 8-hydroxydeoxyguanosine (8OHdG), a marker of oxidative DNA damage, did not differ between the low VE and the basal VE groups. When the rats received TBI at the dose of 3 Gy and were killed on day 6, the levels of HNE, HA and 8OHdG increased by 2.2-, 2-, and 1.5-times, respectively, in the low VE group, but TBI did not cause such increases in the basal VE group. Changes in antioxidative enzymes (glutathione peroxidase, catalase, and Cu/Zn-SOD) in the liver could not explain the different responses of the two diet groups to TBI-induced oxidative damage. The concentrations of vitamin C and glutathione in the liver did not differ between the two groups. These results suggest that dietary VE can prevent the oxidative damage to DNA and lipids in the liver which appear a few days after TBI at dose of 3 Gy.
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PMID:Vitamin E prevents increase in oxidative damage to lipids and DNA in liver of ODS rats given total body X-ray irradiation. 1199 97

Oxidation of lipid, nucleic acids or protein has been suggested to be involved in the etiology of several chronic diseases including cancer, cardiovascular disease, cataract, age-related macular degeneration and aging in general. A large body of research has investigated the potential role of antioxidant nutrients in the prevention of these and other chronic diseases. This review concentrates on the following antioxidant nutrients: beta-carotene and other carotenoids, vitamin E, vitamin C and selenium. The first part of the review emphasizes the utility of biological markers of exposure for these nutrients and the relationship to dietary intake data. The second part considers functional assays of oxidative stress status in humans including the strengths and limitations of various assays available for use in epidemiologic research. A wide variety of functional assays both in vivo and ex vivo, are covered, including various measures of lipid oxidation (thiobarbituric acid reactive substances, exhaled pentane/ethane, low-density lipoprotein resistance to oxidation, isoprostanes), DNA oxidation (oxidized DNA bases such as 8-OHdG, autoantibodies to oxidized DNA, modified Comet assay) and protein oxidation (protein carbonyls). Studies that have examined the effects of antioxidant nutrients on these functional markers are included for illustrative purposes. The review concludes with a discussion of methodologic issues and challenges for studies involving biomarkers of exposure to antioxidant nutrients and of oxidative stress status.
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PMID:Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. 1261 79

The mechanisms of injury- and disease-associated apoptosis of neurons within the CNS are not understood. We used a model of cortical injury in rat and mouse to induce retrograde neuronal apoptosis in thalamus. In this animal model, unilateral ablation of the occipital cortex induces apoptosis of corticopetal projection neurons in the dorsal lateral geniculate nucleus (LGN), by 7 days post-lesion, that is p53 modulated and Bax dependent. We tested the hypothesis that this degenerative process is initiated by oxidative stress and early formation of DNA damage and is accompanied by changes in the levels of pro-apoptotic mediators of cell death. Immunoblotting revealed that the protein profiles of Bax, Bak and Bad were different during the progression of neuronal apoptosis in the LGN. Bax underwent a subcellular redistribution by 1 day post-lesion, while Bak increased later. Bad showed an early sustained increase. Cleaved caspase-3 was elevated maximally at 5 and 6 days. Active caspase-3 underwent a subcellular translocation to the nucleus. A dramatic phosphorylation of p53 was detected at 4 days post-lesion. DNA damage was assessed immunocytochemically as hydroxyl radical adducts (8-hydroxy-2-deoxyguanosine) and single-stranded DNA. Both forms of DNA damage accumulated early in target-deprived LGN neurons. Transgenic overexpression of superoxide dismutase-1 provided significant protection against the apoptosis but antioxidant pharmacotreatments with trolox and ascorbate were ineffective. We conclude that overlapping and sequential signaling pathways are involved in the apoptosis of adult brain neurons and that DNA damage generated by superoxide derivatives is an upstream mechanism for p53-regulated, Bax-dependent apoptosis of target-deprived neurons.
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PMID:Early events of target deprivation/axotomy-induced neuronal apoptosis in vivo: oxidative stress, DNA damage, p53 phosphorylation and subcellular redistribution of death proteins. 1264 45

DNA damage generated by oxygen-derived free radicals is related to mutagenesis, carcinogenesis and aging. In the last several years, hundreds of publications have confirmed that melatonin is a potent endogenous free radical scavenger. In the present in vitro study, we have examined the efficacy of three polyphenolic antioxidants, i.e. xanthurenic acid, resveratrol (3,4',5-trihydroxy-trans-stilbene) and (-)-epigallocatechin-3-gallate (EGCG) and two classical non-polyphenolic antioxidants, i.e. vitamin C (ascorbic acid) and alpha-lipoic acid (LA, 1,2-dithiolane-3-pentanoic acid) in inhibiting *OH-induced oxidative DNA damage. We compared the efficacy of these five antioxidants with the effectiveness of melatonin (N-acetyl-5-methoxytryptamine) and we also investigated the possible synergistic effects of melatonin with the other five molecules. Using high performance liquid chromatography (HPLC), the formation of 8-hydroxy-2-deoxyguanosine (8-OH-dG) in purified calf thymus DNA treated with the Fenton reagents, chromium(III) (as CrCl3) plus hydrogen peroxide (H2O2) (Cr(III)/H2O2), was measured in the presence or absence of the antioxidants alone or in combination with melatonin. 8-OH-dG is considered a biomarker of oxidative DNA damage. Among the antioxidants tested, melatonin was the most effective of these with an IC50 = 3.6 +/- 0.1 micro m. For the other antioxidants the IC50 values were as follows: xanthurenic acid (IC50 = 7.9 +/- 0.3), resveratrol (IC50 = 10.9 +/- 0.3), EGCG (IC50 = 5.7 +/- 0.3), vitamin C (IC50 = 16.9 +/- 0.5) and LA (IC50 = 38.8 +/- 0.7). These values differ from that of melatonin with a P < 0.01. Melatonin (1 micro M) reversed the pro-oxidant effect of resveratrol (0.5 micro M) and vitamin C (0.5 micro M), had an antagonistic effect when used in combination with EGCG (1 micro M) and it exhibited synergism in combination with vitamin C (0.5 micro M) and with LA (5 micro M).
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PMID:Melatonin, xanthurenic acid, resveratrol, EGCG, vitamin C and alpha-lipoic acid differentially reduce oxidative DNA damage induced by Fenton reagents: a study of their individual and synergistic actions. 1266 49

The ingestion of dietary antioxidants, including vitamin C (VC), is suggested to play an important role in the prevention of gastric cancer associated with Helicobacter pylori (HP) infection. Recently, water extracts of Tochu (Du-zhong, Eucommia ulmoidea OLIVER) leaves (WETL) have been reported to have potent antioxidant and antimutagenic effects. The present study investigated the effect(s) of VC and WETL on gastric mucosal injury induced by ammonia and a VC deficient diet. Guinea pigs fed the water containing ammonia and/or a VC-deficient diet were simultaneously treated with WETL or VC. Intramucosal levels of thiobarubiturate reactive substances (TBARS), an index of lipid peroxidation, increased significantly in animals fed ammoniated water and VC-deficient diets. This was accompanied by accelerated cell proliferation and increases in immunohistochemical staining indices for oxidative stress-induced DNA adducts and strand breaks (e.g., BrdU-uptake, 8-OhdG, ssDNA and the TUNEL reaction). The administration of either WETL or VC to the ammoniated water and VC-deficient diets ameliorated the increases in intramucosal TBARS levels and labeling indices of BrdU, 8-OHdG, ssDNA and TUNEL, i.e., the levels were similar to those measured in the normal-fed control animals. These data suggest that insufficient VC ingestion may be an important risk factor for gastric cancer development in patients with HP infections. Furthermore, our results suggest that WETL or some constituent may contribute to the prevention of oxidative gastric injury that precedes carcinogenesis.
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PMID:Tochu (Eucommia ulmoides) leaf extract prevents ammonia and vitamin C deficiency induced gastric mucosal injury. 1456 29

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