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PubMedDate not supplied

Effect of ascorbic acid deficiency on primary and reparative dentinogenesis in non-ascorbate-synthesizing ODS rats.

Ascorbic acid is essential to the biosynthesis of collagen, the major organic matrix component of dentine. The ODS rat is a mutant strain of Wistar rat characterized by hereditary lack of L-gulono-gamma-lactone oxidase and thus is unable to synthesize ascorbic acid. ODS rats were given an ascorbic acid-free diet to investigate how ascorbic acid deficiency affects dentine formation in vivo. Histomorphometric analysis on their growing molars and incisors showed a significant reduction in both size and mineral apposition rate of dentine, as revealed by contact microradiography and fluorescent time-marking, respectively. A similar reduction in bone formation was simultaneously demonstrated in the mandible, confirming the previously reported osteopathic effects of ascorbic acid deficiency. When pulp inflammation was induced in lower first molars by making unsealed pulp exposures, specimens from control animals showed continuous deposition of an osteodentine-like tissue in the radicular pulp chamber; this type of mineralized tissue formation was greatly reduced in ascorbic acid-deprived animals. These results indicate that ascorbic acid deficiency hampers dentine formation under both physiological and pathological conditions of the dentine/pulp complex. ODS rats could be useful in investigating in vivo effects of ascorbic acid deficiency on the formation of dentine and other dental mineralized tissues.

Animals↗
PubMed1991

Ascorbic acid uptake and metabolism by corneal endothelium.

Ascorbic acid is concentrated in various ocular compartments where it is thought to protect diurnal animal species against damaging effects of ultraviolet radiation. The authors evaluated the possibility that corneal endothelial cells have specific transport and/or metabolic properties that deliver ascorbic acid to the stroma. Bovine corneal endothelial cells were grown to confluence in multiple-well plates. Individual groups of cells (approximately 10(4)) were then incubated at various times at 34 degrees C in a physiologic buffer that contained a 10 microM level of 14C-labeled ascorbic acid or the oxidized product, dehydro-L-ascorbic acid. Endothelial cells take up dehydro-L-ascorbic acid at least seven times as rapidly as they take up ascorbic acid. After 30 sec of incubation with 14C-dehydro-L-ascorbic acid, most of the label accumulated in the cell is in the reduced form. Uptake is inhibited by cyanide and iodoacetamide but is unaffected by ouabain. Exposure of cultured cells to various intermediates in the energy metabolism pathways reduced uptake of ascorbic acid but had a minor effect on uptake of the oxidized molecule. These results suggest that the cornea has transport and metabolic capacity to extract dehydro-L-ascorbic acid from aqueous humor and reduce it, thus providing a source of ascorbic acid for corneal protection. This also would maintain "total" ascorbic acid of aqueous humor in the reduced state.

2,3-Diketogulonic Acid↗
PubMed1997

Ascorbic acid and dehydroascorbic acid interconversion without net oxidation or reduction.

The interconversion of ascorbic acid and dehydroascorbic acid was examined in aqueous solution using unlabeled dehydroascorbic acid and nonlabile, stable isotope-labeled ascorbic acid by gas chromatographic/mass spectrometric analysis. Although the formation of unlabeled ascorbic acid from unlabeled dehydroascorbic acid or labeled dehydroascorbic acid from labeled ascorbic acid did not occur to any significant extent when either solutions of unlabeled dehydroascorbic acid or labeled ascorbic acid were incubated alone, significant amounts of both labeled dehydroascorbic acid and unlabeled ascorbic acid formed when unlabeled dehydroascorbic acid was incubated with labeled ascorbic acid at acid pH. At alkaline pH, interconversion did not occur to any appreciable extent. Likewise, interconversion did not appear to occur in plasma at physiologic concentrations of ascorbic acid, but did occur with pharmacologic concentrations. These data show that ascorbic acid and dehydroascorbic acid interconvert in acidic solution, suggesting the reducing hydrogen atoms are delocalized when ascorbic acid is paired with dehydroascorbic acid under these circumstances. Alkaline pH and plasma inhibit the interconversion.

Ascorbic Acid↗
PubMed2003

Iron absorption from ferrous fumarate in adult women is influenced by ascorbic acid but not by Na2EDTA.

Ascorbic acid and Na2EDTA enhance Fe absorption from the water-soluble Fe compound FeSO4 but their effect on poorly water-soluble Fe compounds such as ferrous fumarate is less well established. In the present study, the effects of ascorbic acid and Na2EDTA on Fe absorption from ferrous fumarate were evaluated in adult women (ten women/study) from the erythrocyte incorporation of Fe stable isotopes ((57)Fe or (58)Fe) 14 d after administration. Two separate studies were made with test meals of Fe-fortified infant cereal (5 mg Fe/meal). Data were evaluated by paired t tests and the results are presented as geometric means. In study 1a, the comparison between Fe absorption from ferrous fumarate- and FeSO4-fortified cereal showed that adult women absorb Fe as well from ferrous fumarate as from FeSO4 (3.0 and 3.1 % respectively, P=0.85). After addition of Na2EDTA (Na2EDTA:fortification Fe molar ratio of 1:1), Fe absorption from FeSO4 was significantly higher than from ferrous fumarate (5.3 v. 3.3 % respectively, P<0.01; study 1b). In study 2, Fe absorption was compared from ferrous fumarate-fortified meals with and without ascorbic acid added at a 4:1 molar ratio (relative to fortification Fe) and the results showed that ascorbic acid increased Fe absorption from ferrous fumarate significantly (6.3 v. 10.4 %, P=0.02). The results of the present studies show that Fe absorption from ferrous fumarate is enhanced by ascorbic acid but not by Na2EDTA, thus emphasising that not all findings from Fe absorption studies made with FeSO4 can be extrapolated to Fe compounds with different solubility properties.

Adult↗
PubMed1987

Induction of collagen synthesis by ascorbic acid. A possible mechanism.

L-Ascorbic acid stimulates procollagen synthesis in cultured human skin fibroblasts without appreciably altering noncollagen protein synthesis. The effect is unrelated to intracellular degradation of newly synthesized procollagen. Levels of mRNA for pro alpha 1(I), pro alpha 2(I), and pro alpha 1(III), measured by hybridization with the corresponding cDNA probes, are elevated in the presence of ascorbic acid, whereas the level of mRNA for fibronectin is unchanged. Levels of functional mRNA for procollagen, measured in a cell-free translation assay, are specifically increased in the presence of ascorbic acid. Thus, ascorbic acid appears to control the expression of three different procollagen genes, each of which is located on a separate chromosome. It is proposed that intracellularly accumulated procollagen in ascorbate deficiency may lead to a translational repression of procollagen synthesis. Ascorbic acid may relieve this block by promoting hydroxyproline formation and, consequently, secretion of procollagen from the cell. The increased level of procollagen mRNA under the influence of ascorbic acid may be secondary to increased synthesis of procollagen polypeptides; the control point may be gene transcription or mRNA degradation.

Aging↗
PubMed1992

Site-specific glycation of lens crystallins by ascorbic acid.

The oxidation of ascorbic acid leads to the formation of several compounds which are capable of reacting with protein amino groups via a Maillard reaction. Radioactivity from [1-14C]ascorbic acid was linearly incorporated into lens crystallins over a 10 day period in the presence of NaCNBH3. This rate of incorporation was 6-7-fold more rapid than that obtained with [14C]glucose under the same conditions. SDS-PAGE showed a linear incorporation into all the crystallin subunits. [1-14C]Ascorbic acid-label led alpha-crystallin was separated into its component A and B subunits, and each was digested with chymotrypsin. HPLC peptide analysis showed a differential labelling of the various lysine residues. Analysis of the peptides by mass spectrometry allowed the identification of the sites and the extent of modification. These values ranged from 6% for Lys-78 to 36% for Lys-11 in the A subunit and from 5% for Lys-82 to an average of 38% for the peptide containing Lys-166, Lys-174 and Lys-175 in the B subunit. Amino acid analysis demonstrated a single modification reaction producing N epsilon-(carboxymethyl)lysine. This agreed with the mass increase of 58 observed for each modified peptide.

Amino Acid Sequence↗
PubMed2000

Effects of continuous supplementations of ascorbic acid, aspirin, vitamin E and selenium on some haematological parameters and serum superoxide dismutase level in broiler chickens.

1. This study was conducted using male broiler chickens to determine the effects of ascorbic acid, aspirin, ascorbic acid+aspirin, vitamin E+selenium and ascorbic acid+aspirin+vitamin E+selenium supplementations on haematological parameters and serum superoxide dismutase concentration. 2. One hundred and twenty day-old male Hubbunt broiler chicks were randomly divided into 6 experimental groups of 20 chicks each and placed in different pens. Groups 2, 3, 4, 5 and 6 were given a diet supplemented with ascorbic acid, aspirin (in water), ascorbic acid+aspirin, vitamin E+selenium and ascorbic acid+aspirin+vitamin E+selenium, respectively for 45 d while group 1 was given a commercial broiler diet. 3. There was no significant effect of ascorbic acid, aspirin, ascorbic acid+aspirin, vitamin E+selenium supplementations on any of the haematological parameters (red blood cell, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin concentration, mean corpuscular haemoglobin) in broilers but ascorbic acid+aspirin+vitamin E+selenium supplementation significantly decreased the white blood cell counts. 4. In addition to this, ascorbic acid, aspirin, ascorbic acid+aspirin and ascorbic acid+aspirin+vitamin E+selenium supplementations had no significant effect on the serum superoxide dismutase level, but vitamin E+selenium supplementation increased the serum superoxide dismutase level.

Animals↗
PubMed1994

Enhancement by ascorbic acid 2-glucoside or repeated additions of ascorbate of mitogen-induced IgM and IgG productions by human peripheral blood lymphocytes.

In this study, the effect of ascorbic acid 2-glucoside (AA-2G), a stable derivative of ascorbic acid (AsA), or repeated additions of ascorbate on antibody productions by human peripheral blood lymphocytes (PBLs) was examined, and the physiological function of AsA was evaluated. When human PBLs were stimulated with Staphylococcus aureus Cowan I or pokeweed mitogen, AA-2G remarkably increased the numbers of IgM- and IgG-secreting cells which were detected by enzyme-linked immunospot assay. Although a single addition of ascorbate was without effect, the effect of AA-2G was remarkably inhibited by the addition of castanospermine, an alpha-glucosidase inhibitor; and moreover, repeated additions of AsA to the culture medium during the culture period enhanced the response to the same level as did a single addition of AA-2G. These results indicate that AsA has the ability to stimulate the immunoglobulin productions by AA-2G. The phytohemagglutinin-induced proliferative response of PBLs was also stimulated by AA-2G. The intracellular AsA content in PBLs cultured with AA-2G was maintained at relatively high levels during the culture period, whereas the content with a single dose of AsA reached nearly zero by the end of the experiment. These in vitro findings suggest that AA-2G and AsA function as potent immunostimulators of antibody production in humans and that the intracellular AsA content is a key parameter for establishing the immune response of PBLs.

Antibody Formation↗
PubMed1989

Regeneration of ascorbic acid by rat colon.

Plants and animals alike use ascorbic acid in a variety of reactions that result in net generation of dehydro-L-ascorbic acid. The ability to reduce dehydro-L-ascorbic acid back to ascorbic acid would conserve "total ascorbate" and would help to maintain the toxic oxidized form of the molecule at a low level. This study evaluated the rate of dehydro-L-ascorbic acid reduction either by following the rate of NADPH consumption or by analysis of the amount of 14C-labeled dehydro-L-ascorbic acid converted to ascorbic acid. A large percentage of the NADPH consumed by a semipurified preparation of rat colonic mucosa in vitro was dependent on the presence of dehydro-L-ascorbic acid. The tissue factor active in regenerating ascorbic acid is intermediate in size between cytochrome c and blue dextran. The present results indicate that the mucosa reduced dehydro-L-ascorbic acid by a cytosolic enzyme that uses NADPH as a hydrogen donor. Subsequent to precipitation by ammonium sulfate, the 55-70% fraction contains most of the reductase activity while consisting of only 17% of the cellular soluble protein.

Animals↗
PubMed1984

Pharmacokinetics of ascorbic acid in horses.

The pharmacokinetics of ascorbic acid were studied in 29 horses after intravenous (iv), subcutaneous, intramuscular (im) and oral administration. Following iv injection of 5 and 10 g ascorbic acid, respectively, a biphasic decline of ascorbic acid serum levels was found, indicating that the vitamin distributes in the body according to a two-compartment open model. The apparent volume of distribution (average value for Vd(ss) = 0.6 litre/kg) was approximately equivalent to the volume of total body water. The terminal half-life of the biexponential serum level-time curve (t1/2 beta) varied between 5 and 17 h. Both distribution and elimination were found to be positively correlated with the iv dose administered. Following subcutaneous and im injection, the average bioavailability of ascorbic acid amounted to 82 and 61 per cent, respectively. However, both routes of administration gave rise to marked local irritation. Following oral administration, the systemic availability of ascorbic acid was very poor. Serum levels in most experiments were not increased above the endogenous pre-administration values of the vitamin. Thus, in horses iv injection appears to be the only satisfactory route of administration of ascorbic acid if supplementation is required.

Absorption↗
PubMed1981

Metabolism and requirements of ascorbic acid in man.

The metabolism and absorption of ascorbic acid in man are reviewed. The daily requirement of ascorbic acid in male non-smoking volunteers was studied by following the kinetics of a single dose of (1-14C) ascorbic acid under steady-state conditions. A diet low in vitamin C and daily supplements of ascorbic acid (30-180 mg) were given. The time course of elimination of radioactivity from plasma and urinary excretion data were used to calculate kinetic parameters. The overall half-life was calculated as 10 - 20 days and is dependent of plasma ascorbate levels. The body pool approached 20 mg/kg body weight at a plasma ascorbate concentration of 0.9 mg/dl and was maintained by a total turnover of 60 mg/d. The necessary daily intake of ascorbic acid to match this turnover is 70-80 mg, since absorption is incomplete (80-90%). Therefore, to cover at least 95% of the non-smoking male population a daily intake of 100 mg ascorbic acid is required. Similar studies have been carried out in smokers known to have lowered plasma ascorbate levels. Results suggest that the requirement of ascorbic acid is increased in smokers--a daily intake of 140 mg ascorbic acid is thought to be adequate non-smoking male population a daily intake of 100 mg ascorbic acid is required. Similar studies have been carried out in smokers known to have lowered plasma ascorbate levels. Results suggest that the requirement of ascorbic acid is increased in smokers-a daily intake of 140 mg ascorbic acid is thought to be adequate.

Absorption↗