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Ascorbate-3-sulfate is a significant metabolite of ascorbic acid excreted in human urine. The characteristics of this compound were determined in experiments in which labeling with carbon-14 and tritium was used coupled with cochromatography with synthetic ascorbate-3-sulfate (both labeled and not labeled with sulfur-35) in a variety of solvent and absorbent systems.
Mutagenic activity, ascorbic acid levels and pH were measured in fasting gastric juice from eight patients given oral supplements of vitamin C (1 g qid X 7 days). Supplementation significantly reduced mutagenic activity and increased intragastric ascorbate levels without altering gastric pH. These results demonstrate for the first time the relation between intragastric ascorbate levels, mutagenic activity and oral supplements of vitamin C. The findings are discussed in relation to the possible chemoprevention of gastric cancer.
We have examined the influence of ascorbic acid on the generation of lipoxygenase products by the rabbit cornea, an avascular tissue which is continuously bathed by high concentrations of ascorbic acid present within the aqueous humor of the eye. Corneal homogenates were incubated with [14C]arachidonic acid and the resulting metabolites separated by thin-layer chromatography. The metabolites were then quantified by liquid scintillation counting techniques. The biosynthesis of the major lipoxygenase product formed by the cornea, 12-HETE, was significantly inhibited by physiological concentrations of ascorbic acid; PGE2 formation by the cornea was not altered in the presence of ascorbic acid. Furthermore, ascorbic acid inhibited the formation of 12-HETE in the presence of catalase, indicating that hydrogen peroxide generated by ascorbate was not responsible for diminishing the lipoxygenase activity of the cornea. However, high concentrations of hydrogen peroxide (10(-4) M) did inhibit the formation of 12-HETE by the corneal homogenates. Another antioxidant, 2,6-dichlorophenol-indophenol (10 micrograms ml-1), also inhibited the formation of 12-HETE by the cornea. Therefore, it appears that the inhibition of corneal lipoxygenase by ascorbic acid could be related to the antioxidant properties of this vitamin. These studies suggest that ascorbic acid within the aqueous humor might modulate lipoxygenase activity within the cornea.
Fifty percent of the ascorbic acid content of sliced rat lung was released from the tissue to the media within a few minutes by either washing or incubating the slices with Krebs-phosphate solution. Measurement of the lactate dehydrogenase and potassium content of the medium after incubating lung slices for 5 min showed that about 20% of the cells were damaged by slicing. Sephadex chromatography of tissue extracts prepared from washed lung slices showed that none of the ascorbic acid in these slices were bound to protein. Also, metabolic poisons were shown to deplete the ascorbic acid content of washed lung slices. Approx. 57% of the lung ascorbic acid of guinea pigs that had been supplemented with ascorbic acid and 78% of the lung ascorbic acid of ascorbic acid-deficient guinea pigs were found in the medium when lung slices from these animals were incubated with Krebs-phosphate solution. These results were taken to indicate the presence of an extracellular pool of ascorbic acid in lung which is maintained even during scurvy.
Ascorbic acid concentration was measured in centrifuged and uncentrifuged saliva from normal young adult men and women. The salivary ascorbic acid content of uncentrifuged saliva was significantly higher in women on account of the ascorbic acid contained in the cellular sediment. Ascorbic acid absorption into the buccal mucosa was measured from solutions of pH range 3.4-9.0 held in the mouth for periods of 1-9 minutes. For a constant mouth contact time, increase in pH of the loading solutions resulted in reduction of buccal absorption, and diminishing transfer into the buccal epithelium. Percentage absorption was greater in males than females throughout the pH range. At pH 5, 80% of the loading solution was absorbed after 5 minutes. Diffusion of ascorbic acid through the lipoid membrane was more rapid in males. Female buccal cells had significantly higher ascorbic acid concentrations than male cells. Absorption of laevo and dextro ascorbic acid in human beings can be considered as partitioning into, or passage through, a lipoid phase into the buccal cells. The rate of passage of ascorbic acid into the buccal lining cells under controlled conditions of pH and buccal contact time is pH and concentration dependent in human beings.
L-ascorbic acid is an essential cofactor for lysyl hydroxylase and prolyl hydroxylase, enzymes essential for collagen biosynthesis. In addition, L-ascorbic acid preferentially stimulates collagen synthesis in a manner which appears unrelated to the effect of L-ascorbic acid on hydroxylation reactions. This reaction is stereospecific and unrelated to intracellular degradation of collagen. The effect apparently occurs at a transcriptional or translational level, since L-ascorbic acid preferentially stimulates collagen-specific mRNA. In addition, it stimulates lysyl hydroxylase activity but inhibits prolyl hydroxylase activity in human skin fibroblasts in culture.
Treatment with emetine lowered the ascorbic acid concentrations of serum, liver and kidney, while the ascorbic acid concentration of adrenal tissue remained unaffected. The ability of the liver to synthesize (-)-ascorbic acid from (+)-glucuronolactone was also reduced after emetine treatment. The reduced concentration of ascorbic acid in liver and serum after emetine treatment may result from the diminished synthesis of ascorbic acid by the liver.
Ascorbic acid has been determined quantitatively in a variety of fresh and frozen fruits and vegetables, fresh and fortified canned juices, and powdered drinks by liquid chromatography (LC). The method consists of blending the sample in a solution of 0.05% EDTA in 0.2N H2SO4, centrifuging or filtering the mixture, then injecting a portion into the LC system. An Aminex HPX-87 LC column was used with 0.009N H2SO4 as solvent with a flow rate of 0.5 mL/min. Detection was at 245 nm. The method is simple and sensitive, and yields a high recovery. It compares favorably with the AOAC method, and has the advantage of being more accurate for samples with interfering pigments.
Ascorbic acid was found to be secreted from cultured bovine adrenal chromaffin cells coincidentally with catecholamines using a variety of secretagogues, including veratridine, nicotine, acetylcholine, and potassium chloride. Secretion of ascorbic acid was measured by preloading the cells for 3 h with (R)-[14C]ascorbic acid and then quantitating release of the label. The newly transported ascorbic acid constituted nearly 90% of total cellular ascorbic acid. Although chromaffin granules are known to contain endogenous ascorbic acid, only 16% of the total labeled ascorbic acid taken up by cultured cells was localized to the chromaffin granule fraction. Under the same isolation conditions, 95% of the endogenous catecholamines was found in the granule fraction. The secretion of both (R)-[14C] ascorbic acid and catecholamines was calcium dependent. However, only catecholamine secretion was effectively inhibited by the presence in the medium of isethionate, an impermeant ion that inhibits catecholamine secretion from isolated chromaffin granules. Analysis of the ratios of cellular and granular (R)-[14C] ascorbate as well as secreted (R)-[14C]ascorbate and catecholamines revealed that the secreted (R)-[14C]ascorbic acid did not come exclusively from the chromaffin granule fraction but also from a nonsedimenting cytoplasmic compartment. Indeed, for all four agonists, the amounts of (R)-[14C]ascorbic acid secreted were more than 1.5 times greater than could be accounted for by chromaffin granule ascorbate alone. We took these data to indicate that, while ascorbic acid and catecholamines were secreted concomitantly, the sources of the secreted substances were not necessarily identical.
Vitamin C (ascorbic acid) is an important hydrophilic compound with antioxidative effect. In the introduction the authors describe possible consequences of loss of vitamin C synthetic ability in an evolutionary ancestor of Anthropoidea. Metabolism of this vitamin is described briefly along with possibilities of its supplementation and determination in biological fluids. Highest attention is paid to metabolic effects of vitamin C, respectively to changes which can be observed after its deprivation, or after the supplementation with this vitamin. Protective effect of vitamin C against lipoperoxidation, its role in modulation of immunity and tumorigenesis are described. Many effects of vitamin C can be explained by its antioxidative activity. The authors show that under concrete conditions, administration of vitamin C can be accompanied by a prooxidative effect. Since vitamin C works in cooperation with other antioxidants, its administration in diseases which are followed by oxidative stress is move effective when used in combined preparations.
L-Ascorbic acid (LAA) was shown to modulate the in vitro growth of colonies of human and mouse myeloma progenitor-stem cells through use of a unique cell-culture assay. LAA was also shown to modulate the in vitro growth of leukemic colony-forming cells (L-CFC) from bone marrow of patients with acute myelocytic leukemia. LAA enhanced the growth of L-CFC in 35% of patients and suppressed the growth of L-CFC in 15% of patients. The minimum effective concentration was 0.03 mmol/L. The modulating effect is specific to LAA because other redox compounds are without effect. From the cell kinetic standpoint, the LAA effect is cytostatic rather than cytocidal. Similar LAA effects have prognostic value in patients with myelodysplastic syndromes (MDS), with LAA-sensitive patients displaying shorter survival than LAA-insensitive patients. MDS appears to be the ideal disease for clinical trials involving in vivo LAA manipulation to control the disease process.
Radioactively labelled ascorbic acid and dehydroascorbic acid, when incubated with human blood, migrate irreversibly into human red blood cells. Isolation and characterization of the moieties trapped within the cells via infrared spectroscopy established both their identities as L-ascorbic acid. Evidence in the form of the degree of in vitro entrapment of ascorbic acid as a function of the times of incubation and the effect of incubation temperature, anion recognition site inhibitor, and active transport inhibitor on the rate of entrapment support the hypothesis that ascorbic acid is oxidized on or near the surface of the red blood cell to dehydroascorbic acid which migrates through the lipid portion of the cell wall and is reduced back to ascorbic acid within the cell. The resulting L-ascorbic acid can not pass through the cell wall and is therefore entrapped.
BACKGROUND: Percutaneous absorption of ascorbic acid is limited by its impermeability and instability. OBJECTIVE: We attempted to improve the percutaneous absorption of ascorbic acid by use of iontophoresis after topical application of ascorbic acid. METHODS: Radioactivities extracted from epidermal, dermal and blood compartments after topical application of [14C]ascorbic acid was measured in the presence or absence of iontophoresis. Autoradiography was also performed to study the histological distribution of the radioactivity of ascorbic acid. RESULTS: Iontophoresis greatly enhanced percutaneous absorption of [14C]ascorbic acid in the rat skin. Radioactive ascorbic acid in the dermis reached a maximum level at 1 h after application whereas, in the topical application method, the uptake of ascorbic acid in both epidermis and dermis was quite low. Autoradiography of skin specimens indicated that iontophoresis accelerated the absorption of ascorbic acid through both transepidermal and pilo-sebaceous routes. CONCLUSION: Iontophoretic delivery system of ascorbic acid may provide a more efficient tool for its percutaneous absorption than a simple topical application.
The effect of ascorbic acid on cell size and ascorbic acid transport was studied in hyperoxic astrocytes. Subcultured rat astrocytes plated on poly-L-lysine-coated coverslips or on plastic dishes were exposed to serum-free culture medium and 20% or 42% ambient oxygen for 48 h. Vehicle (homocysteine) or L-ascorbic acid was added to the medium at 0 and 24 h. Cell size and relative optical density of glial fibrillary acidic protein-positive astrocytes were measured by a computerized imaging system. Cells on the dishes were used for ascorbic acid transport studies. Hyperoxia significantly increased the cell size of astrocytes, and this effect was inhibited by ascorbic acid. The rate of L-[14C]ascorbic acid Na(+)-dependent uptake was also inhibited by hyperoxia in vehicle-treated cultures but not in ascorbic acid-supplemented cultures. These results indicate that the presence of ascorbic acid during the hyperoxic episode can prevent astrocytic cell swelling and preserve membrane transport function.
Long-term results of ascorbic acid monotherapy in four young patients with cystine stone complaints are reported. The therapeutic program is based on the descriptions by Asper and Schmucki, who publicized the method for the first time in 1979. Clinical course observations, renal function checks as well as the excretion of cystine, uric acid and oxalic acid during ascorbic acid therapy of our patient pool will be discussed. Clinical observations made to date indicate that ascorbic acid therapy is a practical, inexpensive prophylaxis for cystine stone patients that is virtually free of side effects.
The suppressive effect of L-ascorbic acid on the growth of bone marrow cells from patients with acute nonlymphocytic leukemia was studied using a modified agar culture method featuring daily feeding to allow the growth of leukemic cell colonies. In seven of 28 patients (25%), the numbers of leukemic cell colonies grown in culture were reduced to 21% of control by the addition of L-ascorbic acid (0.3 mM) to the culture medium. Glutathione did not suppress leukemic cell colonies although it has a similar oxidation-reduction potential to that of L-ascorbic acid. The addition of L-ascorbic acid reduced the pH of the medium. However, a comparable reduction of pH by the addition of HCl did not suppress leukemic cell colonies. In simultaneous cultures for leukemic and normal marrow cells, the suppression of leukemic cell colony was noted with a concentration of L-ascorbic acid as low as 0.1 mM (a concentration achievable in vivo), but normal myeloid colonies were not suppressed until the concentration of L-ascorbic acid reached an extremely high level (1 mM). In conclusion, growth of leukemic cells in culture was suppressed by L-ascorbic acid in a substantial proportion of patients with acute nonlymphocytic leukemia. This suppression was a specific effect of L-ascorbic acid and was not due to its oxidation-reduction potential or pH change. Leukemic cells were selectively affected at an L-ascorbic acid concentration attainable in vivo while normal hemopoietic cells were not suppressed.
Ascorbic acid hampers some test systems based on use of peroxidase (EC 1.11.1.7) and redox indicators, by producing a lag time in color development. With reversible indicators, no color development occurs during the ascorbic acid lag time. With oxidatively coupled indicator systems, such as 3-methyl-2-benzothiazolinone hydrazone (MBTH) and a suitable coupler such as chromotropic acid (CTA; 4,5-dihydroxynaphthalene-2,7-disulfonic acid), ascorbic acid diminishes the rate of color development, but does not abolish it. The effect of ascorbic acid strongly depends on the reaction pH as well as the nature of the coupler used. The ascorbate-elicited reduction (or lag) in color development was inversely proportional to the concentrations of MBTH and virtually unaffected by changes in CTA coupler concentration. The rate of color development following the lag was directly proportional to the concentration of MBTH but unaffected by the CTA. These observations suggest that peroxidase with H2O2 catalyzes the oxidation and activation of MBTH to an oxidized species (MBTHox). This species is reduced by ascorbic acid and at the same time couples oxidatively with CTA. Thus, the activity during the ascorbate-induced lag time reflects this competition of ascorbic acid and coupler for MBTHox. This study of peroxidase/ascorbate lag time with the redox coupled indicator system has led to the selection of fast couplers that are highly resistant to interference by ascorbic acid. Suitable resistant couplers (e.g., chromotropic acid, Chicago acid, and H acid) appear to be aromatic ring systems with highly activating substituents and directing toward electrophilic aromatic substitution at the ortho and para positions.
The effect of graded levels of dietary ascorbic acid on blood and tissue ascorbic acid levels in mice has been studied. Six levels of dietary ascorbic acid (0, 0.076, 0.5, 1, 5 and 8%) were used. Plasma ascorbic acid rose as dietary ascorbic acid intake increased from 1 to 8%. Mice fed a diet with 5 or 8% added ascorbic acid had significantly higher levels of ascorbic acid in the heart, kidney, lung, muscle and spleen than did control mice fed an ascorbic acid-free diet. Mice fed a diet with 1% added ascorbic acid had elevated ascorbic acid levels in the heart, kidney, lung and spleen. No significant change was observed in ascorbic acid level in the brain, adrenal gland or leukocytes in any of the experimental groups. Ascorbic acid level in the eyes was only slightly higher in mice fed a diet containing 8% added ascorbic acid than in control mice. The observation that the kidney had the greatest increase in ascorbic acid content suggests that the kidney may be a very important organ not only in elimination but also in catabolism of this vitamin. A diet containing 0.5 or 0.076% added ascorbic acid did not significantly increase ascorbic acid content in any of the organs studied. Mice fed a diet with 0.076% added ascorbic acid had slightly, but statistically significantly, lower levels of ascorbic acid in the liver, lung, muscle and spleen that control mice. Mice fed a diet with 0.5% added ascorbic acid had a lower ascorbic acid content in the liver and muscle than the controls.(ABSTRACT TRUNCATED AT 250 WORDS)