Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dehydroascorbic Acid”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed1991

Ascorbate in the treatment of experimental transplanted melanoma.

Sodium ascorbate supplementation in drinking water inhibited subcutaneous tumor growth, enhanced levodopa methylester (LDME) chemotherapy, and increased survival of B16 melanoma-bearing mice. Antitumor activity was greatest in mice fed diets low in tyrosine and phenylalanine (restricted diet). Ascorbate partially protected against LDME-induced decrease in food intake. Primary tumor masses were smaller, more well defined, and less invasive in ascorbate-supplemented mice, and secondary tumor masses appeared encapsulated. Dehydroascorbate increased tumor growth and decreased survival. Ascorbate supplementation did not alter establishment of experimental B16-BL6 melanoma metastases but inhibited tumor outgrowth when combined with LDME chemotherapy and the restricted diet. Spontaneous metastasis was inhibited by ascorbate in mice fed the restricted diet. Ascorbate supplementation doubled plasma concentration in melanoma-bearing mice independent of diet and increased tumor concentration 3.7-fold (basal diet) and 5.6-fold (restricted diet) relative to unsupplemented mice. Tumor peroxidation also increased during ascorbate supplementation and LDME treatment.

Animals↗
PubMed2004

Duodenal ascorbate levels are changed in mice with altered iron metabolism.

Ascorbate has long been thought to play an important role in intestinal iron absorption. The recent identification of a possible ascorbate-dependent duodenal ferric reductase suggests a role for intracellular ascorbate in the control of iron absorption. We set out to determine whether duodenal ascorbate concentrations are altered by treatments known to alter the rate of iron absorption and whether ascorbate levels affect duodenal reductase activity. Duodenal ascorbate was extracted and assayed by HPLC and/or a chemical assay. Ferric reductase was assayed in vitro with ferric nitrilotriacetate or nitroblue tetrazolium as substrates. Duodenal ascorbate concentrations were increased by iron deficiency, genetic hypotransferrinemia, and hypoxia. Parenteral iron overload increased iron stores but did not affect duodenal ascorbate concentrations. Hemolytic anemia induced in mice by phenylhydrazine injection also did not affect duodenal ascorbate concentrations. In vitro studies with incubated duodenum showed that decreased tissue ascorbate was associated with decreased mucosal ferric reductase activity, whereas incubation with dehydroascorbate prevented both the decrease in ascorbate concentration and reductase activity. Mouse duodenum ascorbate concentrations changed in response to treatments that altered iron absorption rates; in particular, ascorbate levels generally increased when iron absorption was increased by iron deficiency, hypoxia, or genetic hypotransferrinemia. We conclude that changes in ascorbate levels are associated with changes in ferric reductase activity. These findings are consistent with the proposal that duodenal ascorbate plays a role in intestinal iron absorption.

Animals↗
PubMed1999

Glutathione-dependent ascorbate recycling activity of rat serum albumin.

An efficient regeneration of vitamin C (ascorbate) from its oxidized byproduct, dehydroascorbate (DHAA), is necessary to maintain sufficient tissue levels of the reduced form of the vitamin. Additionally, the recycling may be more significant in mammals, such as guinea pigs and humans, who have lost the ability to synthesize ascorbate de novo, than it is in most other mammals who have retained the ability to synthesize the vitamin from glucose. Both a chemical and an enzymatic reduction of DHAA to ascorbate have been proposed. Several reports have appeared in which proteins, including thioltransferase, protein disulfide isomerase, and 3-alpha-hydroxysteroid dehydrogenase, characterized for other activities have been identified as having DHAA reductase activity in vitro. Whether these previously characterized proteins catalyze the reduction of DHAA in vivo is unclear. In the present study, a 66 kD protein was purified strictly on the basis of its DHAA-reductase activity and was identified as rat serum albumin. The protein was further characterized and results support the suggestion that serum albumin acts as an antioxidant and exerts a significant glutathione-dependent DHAA-reductase activity that may be important in the physiologic recycling of ascorbic acid.

Amino Acid Sequence↗
PubMed2002

Differential regulation of hydrogen peroxide and Fas-dependent apoptosis pathways by dehydroascorbate, the oxidized form of vitamin C.

Dehydroascorbate (DHA), the oxidized form of vitamin C (ascorbate), enhanced antioxidant defenses of human T cells preferentially importing DHA over ascorbate. In itself, DHA did not affect cytosolic or mitochondrial reactive oxygen intermediate levels as monitored by flow cytometry using oxidation-sensitive fluorescent probes. DHA at 200-1,000 microM stimulated activity of pentose phosphate pathway enzymes glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and transaldolase, elevated intracellular glutathione levels, and inhibited H(2)O(2)-induced changes in mitochondrial transmembrane potential and cell death. With respect to the CD4 antigen, DHA selectively enhanced cell-surface expression of the Fas receptor and increased susceptibility of Jurkat and H9 human T cells to Fas-mediated cell death. The data identify DHA as a selective regulator of H(2)O(2)- and Fas-dependent apoptosis pathways.

Animals↗
PubMed1993

Redox metabolism of vitamin C in blood of normal and malaria-infected mice.

As oxidative mechanisms have been suggested to be part of the host immune reaction against malarial parasites, we investigated the redox metabolism of the antioxidant vitamin C in the blood of control and malaria-infected mice. At the peak of infection (day 6) with the malaria parasite P. vinckei, plasma levels of ascorbate (AH-) were 10.8 +/- 0.9 micrograms/ml compared to 5.7 +/- 0.7 micrograms/ml in control mice, though no significant change was observed in the plasma concentration of dehydroascorbate (DHA). The plasma redox ratio of vitamin C, [AH-]:[DHA], was 7.4 in control mice and 18.5 in infected mice on day 6 post-inoculation. The increased AH- level in plasma of P. vinckei-infected mice was not due to differences in stabilities of either AH- or DHA in plasmas from control or P. vinckei-infected mice. DHA added to plasma was lost rapidly. In contrast, when added to whole blood. DHA was rapidly taken up and reduced to AH by blood cells from both normal mice and P. vinckei-infected mice. Most of the intracellular AH- derived from the exogenously added DHA was released into the plasma by blood cells from the infected but not normal mice. The observed release of AH- into the plasma by blood cells from infected mice was not caused by a plasma factor. Depletion of leukocytes from erythrocytes had no effect on the uptake and reduction of DHA by red blood cells, but the subsequent release of intracellular AH- occurred more rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Networking antioxidants in the isolated rat heart are selectively depleted by ischemia-reperfusion.

Although cardiac endogenous antioxidants have been reported to be oxidized and decreased by ischemia-reperfusion, little is known whether the changes in these antioxidants are correlated with each other in a systematic relationship. In this study, isolated rat hearts were subjected to various periods of ischemia-reperfusion using the Langendorff method, and the content and/or redox status of tissue antioxidants were analyzed. Significant losses in the tissue hydrophilic antioxidants, ascorbate, and glutathione were observed. These losses were dependent on the duration of the reperfusion period (between 0-40 min) but not of ischemia (20-60 min). Marked increases of dehydroascorbate and glutathione disulfide, the oxidized forms of ascorbate and glutathione, respectively, were found during reperfusion, but these changes were not observed during ischemia. These findings indicate that the tissue hydrophilic antioxidants are easily oxidized and may be the first line of antioxidant defenses during reperfusion. Lipophilic antioxidants, like ubiquinol 9 and vitamin E, were not decreased during ischemia-reperfusion using regular buffer; however, if oxidative stress was induced by addition of H2O2 to the buffer solution during reperfusion after 20 min of ischemia, decreases in both the hydrophilic and hydrophobic antioxidants were noticeable. With 100 microM H2O2, the tissue antioxidant decreases were ubiquinol 9 (39%), vitamin E (3%), glutathione (44%) and ascorbate (58%). Only with 500 microM H2O2 treatment were marked decreases in tissue vitamin E (65%) observed; this was associated with almost complete depletion of tissue ubiquinol 9 (95%). These results suggest that prior to the consumption of vitamin E, other antioxidants are depleted and that vitamin E may serve as the ultimate antioxidant, protecting the integrity of cellular membranes. Thus, in this work, cardiac antioxidants were demonstrated to change in a systematically organized relationship under ischemia-reperfusion. This graded utilization of antioxidants supports the redox based antioxidant network concept, found to be present in other biological systems.

Animals↗
PubMed1994

Determination of superoxide and ascorbyl radicals in the circulation of animals under oxidative stress.

Quantitation of the superoxide radical and its related metabolites in vivo is practically difficult predominantly because of their short biological half-lives. Though oxidized cytochrome c (cyt c) has been used for determining superoxide radicals in vitro, it cannot be used for in vivo analysis because of its low specificity as an electron acceptor and rapid disappearance from the circulation. To measure superoxide radicals and related metabolites in normal and pathologic subjects, we have synthesized a cyt c derivative (SMAC) with prolonged half-life in the circulation (T1/2 = 130 min) by conjugating acetylated cyt c with poly(styreneco-maleic acid) butyl ester (SM). An SM-conjugated superoxide dismutase (SM-SOD) with prolonged in vivo half-life was also synthesized. When injected intravenously to the rat, SMAC was rapidly reduced in the circulation of normal rats. The rate of SMAC reduction was markedly increased by intravenous administration of menadione, a compound capable of redox cycling and generating superoxide. The rate of SMAC reduction was not inhibited by a large dose of SM-SOD (27,000 unit/kg) in both normal and menadione-treated animals. The rate of SMAC reduction also increased in animals which were administered alloxan, a diabetogenic agents. In contrast to the experiments with menadione, the alloxan-enhanced reduction of SMAC was significantly inhibited by SM-SOD. Kinetic analysis using ascorbate oxidase suggested that ascorbyl radical was principally responsible for the SM-SOD-insensitive reduction of SMAC. Streptozotocin, another diabetogenic agent, failed to increase the rate of SMAC reduction. Thus, the effect of streptozotocin on the redox state of animals and the mechanism of its diabetogenic action might differ from those of alloxan. Combined use of SMAC and SM-SOD might permit quantitative studies on the occurrence of ascorbyl and superoxide radicals in the circulation of animals challenged with oxidative stress.

Acetylation↗
PubMed2000

Glutathione deficiency potentiates manganese-induced increases in compounds associated with high-energy phosphate degradation in discrete brain areas of young and aged rats.

Aging is a factor known to increase neuronal vulnerability to oxidative stress, which is widely accepted as a mechanism of manganese-induced neuronal damage. We previously showed that subchronic exposure to manganese induced greater energy impairment (as revealed by increases in hypoxanthine, xanthine and uric acid levels) in the striatum and brainstem of aged rats vs young rats. This study shows that inhibition of glutathione (GSH) synthesis, by means of buthionine (SR) sulfoximine, decreased GSH levels and increased the ascorbic acid oxidation status in the striatum and limbic forebrain of both young and aged rats. In addition, inhibition of GSH synthesis greatly potentiated the manganese-induced increase in inosine, hypoxanthine, xanthine and uric acid levels in both regions of aged rats; moreover, inhibition of GSH synthesis significantly increased inosine, hypoxanthine, xanthine and uric acid levels in both regions of young rats, compared with the manganese-treated group. These results suggest that an impairment in the neuronal antioxidant system renders young rats susceptible to manganese-induced energetic impairment, and further support the hypothesis that an impairment in this system plays a permissive role in the increase of neuronal vulnerability that occurs with aging.

Aging↗
PubMed2002

Hydroponically cultivated radish fed L-galactono-1,4-lactone exhibit increased tolerance to ozone.

Leaf L-ascorbate content of an ozone (O3)-sensitive radish genotype (Raphanus sativus L. cv. Cherry Belle) was increased 2-fold by feeding hydroponically cultivated plants L-galactono- 1,4-lactone (GalL). Plants were grown in controlled-environment chambers ventilated with charcoal/Purafil-filtered air, and administered one of two O3 fumigation regimes: chronic exposure (75 nmol O3 mol(-1) for 7 h day(-1) for 21 days) and acute exposure (180 nmol O3 mol(-1) for 9 h). Chronic O3 exposure decreased root growth by 11% in plants maintained in pure nutrient solution (-GalL), but resulted in no change in root growth in GalL-fed plants (+GalL). Similarly, GalL-feeding counteracted the negative effects of O3 on CO2 assimilation rate observed in control plants (-GalL). Under acute O3 exposure, GalL-fed plants showed none of the visible symptoms of injury, which were extensive in plants not fed GalL. Leaf CO2 assimilation rate was decreased by acute 03 exposure in both GalL treatments, but the extent of the decline was less marked in GalL-fed plants. No significant changes in stomatal conductance resulted from GalL treatment, so O3 Uptake into leaves was equivalent in + GalL and -GalL plants. Feeding GalL, on the other hand, enhanced the level of ascorbate, and resulted in the maintenance of the redox state of ascorbate under acute O3 fumigation, in both the leaf apoplast and symplast. The effect of GalL treatment on ascorbate pools was consistent with the reduction in O3 damage observed in GalL-fed plants. Attempts to model O3 interception by the ascorbate pool in the leaf apoplast suggested a greater capacity for O3 detoxification in GalL-fed plants, which corresponded with the increase in O3 tolerance observed. However, modelled data for GalL-fed plants suggested that additional constituents of the leaf apoplast may play an important role in the attenuation of environmentally-relevant O3 fluxes.

Air Pollutants↗
PubMed2006

The effect of intracellular ascorbate on the susceptibility of HL60 and Jurkat cells to chemotherapy agents.

Chemotherapy agents initiate tumour cell apoptosis and this is thought to involve oxidative stress. In this study we have investigated the effect of the important antioxidant Vitamin C (ascorbate) on the response of HL60 and Jurkat cells to three chemotherapy drugs, namely etoposide, melphalan and arsenic trioxide (As(2)O(3)). Cells grown in routine culture media are deficient in ascorbate and to determine its effect on chemotherapy drug-induced apoptosis we supplemented the cells prior to drug exposure. We found that ascorbate had a varied effect on apoptosis and cell cycle progression. Etoposide-induced apoptosis in HL60 cells was significantly increased in ascorbate-loaded cells as measured by caspase-3 activation and DNA degradation, and this appeared to reflect a decrease in the number of necrotic cells rather than increased cytotoxicity. In contrast, ascorbate had no effect on etoposide-induced apoptosis in Jurkat cells. In both cell types melphalan-induced apoptosis was unaffected by intracellular ascorbate, whereas both apoptosis and growth arrest with low concentrations of As(2)O(3) were diminished. These results indicate that intracellular ascorbate can affect cell responses to chemotherapy drugs in a complex and somewhat unpredictable manner and that it may play an important role in the responsiveness of tumour cells to chemotherapy regimes.

Antineoplastic Agents↗
PubMed1987

Solubility properties of reduced and oxidized ascorbate as determinants of membrane permeation.

The oil/water distribution coefficients of ascorbic acid and dehydro-L-ascorbic acid have been determined and compared with values for mannitol and lauric acid. In general, the relative degrees of hydrophobicity of the compounds evaluated are lauric acid much greater than mannitol approximately equal to dehydro-L-ascorbic acid greater than ascorbic acid. These findings and recent reports from transport studies do not support the concept that dehydro-L-ascorbic acid is very hydrophobic and crosses cell membranes rapidly by simple diffusion.

Ascorbic Acid↗
PubMed2002

Exploring the active site of plant glutaredoxin by site-directed mutagenesis.

Six mutants (Y26A, C27S, Y29F, Y29P, C30S and Y26W/Y29P) have been engineered in order to explore the active site of poplar glutaredoxin (Grx) (Y26CPYC30). The cysteinic mutants indicate that Cys 27 is the primary nucleophile. Phe is a good substitute for Tyr 29, but the Y29P mutant was inactive. The Y26A mutation caused a moderate loss of activity. The YCPPC and WCPPC mutations did not improve the reactivity of Grx with the chloroplastic NADP-malate dehydrogenase, a well known target of thioredoxins (Trxs). The results are discussed in relation with the known biochemical properties of Grx and Trx.

Amino Acid Sequence↗
PubMed1999

Inhibition of copper-induced LDL oxidation by vitamin C is associated with decreased copper-binding to LDL and 2-oxo-histidine formation.

Oxidatively modified low-density lipoprotein (LDL) has numerous atherogenic properties, and antioxidants that can prevent LDL oxidation may act as antiatherogens. We have previously shown that vitamin C (L-ascorbic acid, AA) and its two-electron oxidation product dehydro-L-ascorbic acid (DHA) strongly inhibit copper (Cu)-induced LDL oxidation. These findings are unusual, as AA is known to act not only as an antioxidant, but also a pro-oxidant in the presence of transition metal ions in vitro, and DHA has no known reducing capacity. Here we report that human LDL (0.4 mg protein/ml) incubated with 40 microM Cu2+ binds 28.0 +/- 3.3 Cu ions per LDL particle (mean +/- SD, n = 10). Co-incubation of LDL with AA or DHA led to the time- and concentration-dependent release of up to 70% of bound Cu, which was associated with the inhibition of LDL oxidation. Incubation of LDL with Cu and AA or DHA also led to the time-dependent formation of 2-oxo-histidine, an oxidized derivative of histidine with a low affinity for Cu. Addition of free histidine prevented the formation of the LDL-Cu complexes and inhibited LDL oxidation, despite the fact that Cu remained redox-active. Interestingly, histidine was more effective than AA or DHA at limiting Cu binding to LDL, but at low concentrations AA and DHA were more effective than histidine at inhibiting LDL oxidation. These data suggest that there are at least two types of Cu binding sites on LDL: those that bind Cu in a redox-active form critical for initiation of LDL oxidation, and those that bind Cu in a redox-inactive form not contributing to LDL oxidation. The former sites may be primarily histidine residues of apolipoprotein B-100 that are oxidized to 2-oxo-histidine in the presence of Cu and AA or DHA, thus explaining, at least in part, the unusual inhibitory effect of vitamin C on Cu-induced LDL oxidation.

Antioxidants↗
PubMed1996

One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: redox reaction involving ergothioneine and vitamin C.

Redox reactions of endogenous and exogenous sulphur-containing compounds are involved in protection against oxidative damage arising from the incidence and/or treatment of many diseases, including cancer. We have investigated, via pulse radiolysis, the one-electron oxidation of ergothioneine, a molecule with antioxidant properties which is detected at millimolar concentrations in certain tissues and fluids subject to oxidative stress, including erythrocytes and plasma. The spectrum of the transient species, assigned to the product of one-electron oxidation, observed after reaction of ergothioneine with the oxidizing radicals OH., N3. and CCl3O2. has a maximum absorption at 520 nm and is very similar to that obtained by oxidation of analogous molecules such as 2-mercaptoimidazole, 1-methyl-2-mercaptoimidazole, S-methyl- and S,N-dimethyl-ergothioneine. In the presence of vitamin C, the oxidized form of ergothioneine is repaired by a rapid reduction (k = 6.3 x 10(8) M(-1).s(-1)) producing ascorbyl radicals. This co-operative interaction between ergothionine and ascorbate, similar to that previously observed between vitamin E and ascorbate, may contribute to essential biological redox protection.

Antioxidants↗
PubMed1998

Plasma and platelet ascorbate pools and lipid peroxidation in insulin-dependent diabetes mellitus.

BACKGROUND: As diabetes mellitus represents a situation in which production of peroxides is increased, the aim of this study was to investigate the relationship between plasma and platelet levels of ascorbic acid (AA)/dehydroascorbic acid (DHA) and those of malonyldialdehyde (MDA), an indirect marker of lipoperoxides, both assayed using high-performance liquid chromatography (HPLC), in 59 patients with insulin-dependent diabetes mellitus (IDDM) compared with 51 healthy control subjects matched for sex, age, smoking habits, as well as for dietary intake of energy, alcohol and vitamin C. RESULTS: Mean plasma and platelet MDA were significantly higher in the patients affected with IDDM than in control subjects. Moreover, the diabetic group was characterized by a huge decrease in plasma AA [8.45 +/- 5.5 mumol L-1 (SD) vs. 33.4 +/- 7.6 mumol L-1, P = 0.0001], mirrored by a significant increase in plasma DHA (11.9 +/- 3.9 mumol L-1 vs. 3.9 +/- 2.5 mumol L-1, P = 0.0001). No detectable DHA was observed in the platelets from both diabetic and control subjects, whereas AA was significantly increased in platelets from diabetic patients compared with control subjects (42.6 +/- 7.4 vs. 34.8 +/- 5.1 nmol 10(-9) platelets, P = 0.0001). Platelet AA in the diabetic group was significantly inversely correlated with glycated haemoglobin (r = -0.34; P = 0.04) and directly with plasma AA (r = 0.39; P = 0.02), the sum of plasma AA + DHA (r = 0.44; P = 0.009) and with platelet MDA (r = 0.38; P = 0.02). CONCLUSION: (a) The ratio plasma AA/DHA is significantly lowered in IDDM in association with an increase in MDA levels; (b) only AA is detected in platelets, being augmented in the diabetic group; (c) plasma ascorbate depletion does not reflect platelet levels of AA; and, finally, (d) metabolic control, as well as intracellular lipoperoxides, modulates platelet AA in IDDM.

Adult↗
PubMed2000

The competition between methyl viologen and monodehydroascorbate radical as electron acceptors in spinach thylakoids and intact chloroplasts.

In spinach thylakoids prepared from intact chloroplasts by shocking in the presence of ascorbate to preserve the operation of ascorbate peroxidase, the rate of oxygen uptake with methyl viologen as acceptor decreased in response to the addition of H2O2. Such a decrease was not observed in the presence of KCN or when the thylakoids lost ascorbate peroxidase activity. Illumination of intact chloroplasts in the presence of H2O2 and methyl viologen showed an initial rate of oxygen exchange, which is intermediate between the initial rate of oxygen evolution in the presence of H2O2 alone and steady-state oxygen uptake in the presence of methyl viologen. The data showed that monodehydroascorbate radical generated in ascorbate peroxidase reaction could compete with methyl viologen for electrons supplied by the electron transport chain in both thylakoids and intact chloroplasts. During the illumination of intact chloroplasts the rate of oxygen uptake increased. The presence of nigericin swiftly led to steady-state oxygen uptake, and to a clear-cut 1:1 relationship between the electron transport rate estimated from fluorescence assay and the electron transport rate determined from oxygen uptake, taking the stoichiometry 1 O2:4 e. The increase in oxygen uptake was attributed to the cessation of monodehydroascorbate radical generation brought about by consumption of intrachloroplast ascorbate in the peroxidase reactions, and the effects of nigericin were explained by acceleration of such consumption. The competition between methyl viologen and monodehydroascorbate radical in the intact chloroplasts was estimated under various conditions.

Ascorbate Peroxidases↗
PubMed2000

Glucose modulates vitamin C transport in adult human small intestinal brush border membrane vesicles.

The uptake of L-ascorbate (vitamin C) and its oxidized form, dehydro-L-ascorbic acid (DHAA), was evaluated in brush border membrane vesicles isolated from adult human duodenum, jejunum and ileum. Ascorbate was taken up along the entire length of the small intestine with a threefold higher initial uptake rate in distal than proximal segments. Ascorbate uptake was Na(+)-dependent, potential-sensitive and saturable (K(m), 200 micromol/L), whereas DHAA transport involved facilitated diffusion (K(m), 800 micromol/L). Pharmacologic experiments were conducted to characterize further these transport mechanisms. DHAA uptake was not mediated by the fructose carrier GLUT5, the uridine transporter or the 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-sensitive anion exchanger of the apical membrane. DIDS and sulfinpyrazone, an inhibitor of the urate/lactate exchanger, both significantly reduced the initial rate of ascorbate uptake. Acidic pH inhibited ascorbate uptake, and this effect was not due to a transmembrane proton gradient. Increasing concentrations of glucose in the transport media also significantly inhibited ascorbate uptake, but no effect of glucose was seen when glucose internalization was blocked by phlorizin. Preloading the vesicles with glucose inhibited ascorbate uptake similarly, indicating that glucose interferes with the ascorbate transporter from the internal side of the membrane. The results of this study suggest that DHAA crosses the apical membrane by facilitated diffusion, whereas ascorbate transport is a Na(+)-dependent, electrogenic process modulated by glucose.

Adult↗