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In vivo effect of ascorbic acid on neutrophil function in healthy and dexamethasone-treated cattle.

Ascorbic acid (20 mg/kg of body weight) administered subcutaneously to otherwise nontreated cattle resulted in enhancement of neutrophil oxidative metabolism and capability of neutrophils to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Random migration, bacterial ingestion, and iodination by neutrophils was unaffected. Three dosage levels of ascorbic acid (10 mg/kg, 20 mg/kg, and 40 mg/kg) were examined for their effects on neutrophil function in cattle treated with dexamethasone (0.04 mg/kg). Dexamethasone administration caused an enhancement of neutrophil random migration and a suppression of neutrophil oxidative metabolism, iodination, and ADCC. None of the dosage levels of ascorbic acid had an effect on the alterations in the WBC count induced by dexamethasone. The ascorbic acid did tend to reverse the effects of dexamethasone on neutrophil random migration, oxidative metabolism, and ADCC in a dose-dependent manner, with the lowest dose having no discernible effect. Ascorbic acid administration also tended to enhance Staphylococcus aureus ingestion by bovine neutrophils. These results indicate that ascorbic acid should be further investigated for its potential to reduce the susceptibility of stressed or glucocorticoid-treated cattle to infective processes.

Animals↗

Antioxidant activity of 6-phosphatidyl-L-ascorbic acid.

The antioxidant activity of 6-phosphatidyl-L-ascorbic acid was investigated in a homogeneous solution and a liposomal suspension. In an apolar solvent, one molecule of 6-phosphatidyl-L-ascorbic acid could trap one peroxyl radical. When 6-phosphatidyl-L-ascorbic acid was included in multilamellar liposomes of egg yolk phosphatidylcholine, it could retard more effectively the aqueous peroxyl-induced peroxidation of phosphatidylcholine than L-ascorbic acid.

Antioxidants↗

Concentration gradients for HVA, 5-HIAA, ascorbic acid, and uric acid in cerebrospinal fluid.

Concentrations of HVA, 5-HIAA, ascorbic acid, and uric acid in the lumbar and cisternal cerebrospinal fluid (CSF) were measured in psychiatric and neurologically impaired patients. The concentration of HVA is 6.1 times and of 5-HIAA 2.7 times higher in cisternal than in lumbar samples, the cisternal level of uric acid is half that of the lumbar region, but no significant differences were found in ascorbic acid concentrations. Correlation between lumbar and cisternal metabolite concentrations is high for 5-HIAA and ascorbic acid, and is less for HVA and uric acid. In cisternal CSF there is a significant correlation between levels of HVA-5-HIAA, 5-HIAA-ascorbic acid, and 5-HIAA-uric acid. These correlations disappear in lumbar CSF. These findings indicate that extrapolations to cisternal neurotransmitter metabolite concentration from lumbar measures are unwarranted for HVA, but not for 5-HIAA.

Adult↗

Solubilization of hydrophobic drugs in octanoyl-6-O-ascorbic acid micellar dispersions.

Alkanoyl-6-O-ascorbic acid esters are easily obtained from vitamin C, and produce self-assembled aggregates in water solutions, with an inner hydrophobic pool surrounded by an external hydrophilic shell. Compared to ascorbic acid, their solubility in oils and fats is greatly enhanced, while the peculiar antioxidant activity is retained in the polar head groups of such surfactants. In virtue of their amphiphilic nature, ascorbic acid-based supramolecular systems can dissolve relevant amounts of hydrophobic, poorly water soluble chemicals such as drugs, vitamins, and so on, and at the same time they provide a suitable shield against oxidative deterioration of valuable materials. In this article we report our study on the self-assembling properties of octanoyl-6-O-ascorbic acid in water, and on the solubilization of some lipophilic molecules in its dispersions.

Antioxidants↗

Effect of diet on growth and plasma ascorbic acid in chicks.

Six experiments were conducted to study the effect of diet on growth and plasma ascorbic acid in chickens. D-Glucuronolactone failed to improve growth with either a crude yeast-fish meal diet or a purified diet based on casein and gelatin. With the purified diet, D-glucuronic acid and L-gulonolactone also failed to improve growth and did not influence plasma ascorbic acid levels. Dietary ascorbic acid improved growth of chicks with a purified diet in most cases, but not with a corn-soybean diet. Meat meal and fish meal caused slight increases in plasma ascorbic acid, whereas soybean meal, safflower meal, and cottonseed meal caused greater increases when used in a purified diet. Gulonolactone oxidase activity in the kidney was not different between chicks fed the purified or the corn-soybean diets, but was reduced by 0.1% dietary ascorbic acid. The mechanism for the increase in plasma ascorbic acid with the addition of soybean meal and other plant protein sources to the diet is not known.

Animals↗

Effect of prolonged marginal ascorbic acid deficiency on lenticular levels of antioxidants and lipid peroxide in guinea pigs.

We examined the effect of prolonged marginal ascorbic acid deficiency of the levels of antioxidants and lipid peroxide in lenses of guinea pigs in order to clarify lenticular antioxidant status under ascorbic acid deficiency. Male guinea pigs aged 4 weeks were given a scorbutic diet (20 g/animal per day) with either marginally deficient ascorbic acid (0.5 mg/animal per day) or sufficient ascorbic acid (1 g/animal per day) in drinking water for 3 and 6 months. The deficient group showed no lens opacity during the administration period. The deficient group had 62.3 and 53.9% of lenticular ascorbic acid content in the sufficient group at 3 and 6 months of ascorbic acid deficiency, respectively. There were no differences in lenticular contents of reduced glutathione and thiobarbituric acid reactive substances, an index of lipid peroxidation, between both groups at 3 and 6 months of ascorbic acid deficiency, while the deficient group tended to have higher lenticular vitamin E content than the sufficient group. The deficient group had higher serum vitamin E concentration than the sufficient group at 3 and 6 months of ascorbic acid deficiency. These results indicate that lenticular antioxidant status is maintained well in guinea pigs with prolonged marginal ascorbic acid deficiency, which may result in no cataract formation.

Animals↗

Carbon nanotube-modified electrodes for the simultaneous determination of dopamine and ascorbic acid.

The voltammetric separation of dopamine and ascorbic acid was studied with cyclic voltammetry at two kinds of carbon nanotube-modified electrodes (coated and intercalated). The anodic peak difference reached 270 mV under the present conditions. The separation mechanism and effect factors were carefully studied. Using various types of surfactants as coating dispersants of carbon nanotubes, it was demonstrated that the charge nature of the surfactants had a strong effect on the electrochemical behavior of dopamine and ascorbic acid. When the oxidation solution of carbon nanotubes was changed from the most commonly used mixed concentrated nitric acid and sulfuric acid (1 + 3 v/v) to dilute nitric acid and to hydrochloric acid, the anodic peak separation value of dopamine and ascorbic acid increased significantly, and it was shown that carboxylic acid groups attached to the carbon nanotubes were an adverse factor for the discrimination of DA from AA. These results indicated that the resolution of DA and AA was mainly attributable to the stereo porous interfacial layer formed from aggregated pores and inner cavities of the carbon nanotubes. The modified electrodes exhibited an attractive ability to measure DA and AA simultaneously and showed good stability and reproducibility.

Ascorbic Acid↗

Significance of the equilibrium constant between serum ascorbate radical and ascorbic acids in man.

The spin concentration of ascorbate radical in human serum was examined and the existence of the stable equilibrium between the spin concentration of serum ascorbate radical and concentrations of ascorbic acids in healthy subjects was found. The value of the equilibrium constant was independent of age and sex. The administration of ascorbic acid caused the convergence of these values which were scattered within certain ranges in healthy volunteers. The values of the equilibrium constant increased in many patients with various diseases and returned to normal level with improvement of symptoms. These indicate that the equilibrium constant can be used as a clinical index to reflect metabolic state involving ascorbic acid as the radical scavenger.

Ascorbic Acid↗

Glucose inhibits cellular ascorbic acid uptake by fibroblasts in vitro.

It has been suggested earlier that the local deficiency of ascorbic acid in tissues could be responsible for development of various angiopathies in diabetes. Hyperglycemia is one of the factors which could contribute considerably to the development of local ascorbic acid deficiency. Therefore, the effect of glucose on uptake of L-[1-14C] ascorbic acid by fibroblasts was studied in vitro. The data clearly show that ascorbic acid uptake is inhibited instantly by glucose in a concentration dependent fashion. The results support the contention that local ascorbic acid deficiency in tissues could be a natural consequence of hyperglycemia of whatever cause. The rate of ascorbic acid uptake under various conditions suggests that additional supplements of ascorbic acid might be helpful to individuals in averting deleterious effects of hyperglycemia on tissue ascorbic acid supply.

Animals↗

Microencapsulation of ascorbic acid: effect of process variables on product characteristics.

This study deals with a comparative investigation of the characteristics of ascorbic acid microcapsules prepared by different methods, such as thermal phase separation, melt dispersion, solvent evaporation and spray drying. Scanning electron microscopy (SEM), release tests and size distribution were used for the evaluation of product characteristics. The results show that microencapsulated ascorbic acid could prevent the ascorbic acid colour change, retard its core release rate, and generally mask its acid taste. In the thermal phase separation, molecular weight (Mw) of ethyl cellulose (EC) and the addition of polyisobutylene (PIB) significantly influenced the aggregation and release rate of microcapsules. In the melt dispersion method, spherical particles were prepared by using carnauba. The ascorbic acid release rate was found to be slower in the case of carnauba-encapsulated ascorbic acid than that made by EC using other methods. In the solvent evaporation method, a higher Mw of EC and the addition of plastizer were also found to be important for good encapsulation. In the spray drying method, loss of ascorbic acid was found to be minimum during microencapsulation. Starch and beta-cyclodextrin encapsulated ascorbic acid delayed the degradation of ascorbic acid during storage at 38 degrees C and relative humidity 84.0%.

Antioxidants↗

Concentrations of low and high molecular weight thiols in wheat dough as affected by different concentrations of ascorbic acid.

Different amounts of ascorbic acid (AA) were added to flour, and the concentrations of low and high molecular weight thiols in the dough were determined. For the determination of the low molecular weight thiols, glutathione, cysteine, and the corresponding disulfides, an isotope dilution assay with a (14)C-labeled internal standard was used. For the determination of the high molecular weight thiols, a method was developed that involved derivatization of dough with Ellman's reagent, removal of excess reagent by dialysis, micro-Osborne fractionation, release of the label by reduction, and determination of reduced Ellman's reagent by reversed-phase high-performance liquid chromatography. Mixing of flour without AA led to a decrease of the glutathione and an increase of the cysteine concentration. Addition of AA reduced the concentration of both thiols to a minimum when 125 mg of AA/kg of flour was applied. Furthermore, the concentrations of high molecular weight thiols in the glutenins of flours from different wheat cultivars were determined. The values ranged from 5.6 to 8.2 micromol/kg of protein and showed a correlation between flour quality and SH concentration. On addition of AA and mixing of a dough, the concentrations of the protein thiols in the glutenins isolated from the dough increased to a maximum when 100 mg of AA/kg of flour was added. Higher concentrations of AA led to a decrease of the SH concentration. The last results are not in accordance with previously published data or with current hypotheses about the mechanism of the AA improver action.

Ascorbic Acid↗

Antimutagenic and promutagenic activity of ascorbic acid during oxidative stress.

Ascorbic acid (AA) has both antioxidant and prooxidant activities. However, there have not been any studies to elucidate the molecular mechanisms that determine whether AA functions as an anti- or a prooxidant during oxidative stress. The results of this study, using the Chinese hamster ovary cell line AS52 as a model system, demonstrate that there is a temporal relationship between the anti- and prooxidant activities of a physiologically relevant concentration of AA (50 microM) and oxidative stress. Treatment of cells with AA (50 microM) 24 hr prior to treatment of the cells with a radical generating system (RGS) results in a statistically significant inhibition of the cytotoxicity and mutagenicity associated with exposure of AS52 cells to oxidative stress. Conversely, cotreatment of cells with AA and the RGS results in a statistically significant increase in both the cytotoxic and mutagenic effects of oxidative stress when compared to cell populations exposed only to the RGS. The results, using a novel histochemical-computer image analysis system to detect hydrogen peroxide (H2O2), also demonstrate that there is a direct correlation between the ability of AA to decrease the levels of H2O2 in cells and the cytotoxic and mutagenic effects of oxidative stress. This study suggests that the time at which AA is administered in relation to exposure to oxidative stress has an impact on AA antimutagenic activity, and this may explain the conflicting results concerning the effectiveness of AA as a cancer chemopreventive agent.

Animals↗

L-gulono-gamma-lactone oxidase is not induced in rats by xenobiotics stimulating L-ascorbic acid biosynthesis.

L-Ascorbic acid (AsA) is synthesized from D-glucose in rats; the terminal step of this synthetic pathway is catalyzed by L-gulono-gamma-lactone oxidase (GLO). In this study, we examined the effects of phenobarbital (PB) and 3-methylcholanthrene (MC), both of which are known to stimulate AsA biosynthesis in rats, on the hepatic levels of GLO activity, GLO mRNA, and AsA. Firstly, the existence of GLO mRNA was examined in the liver, kidney, lung, small intestine, spleen, testis, and prostate from a male rat; and GLO mRNA was found to be present only in the liver, in which GLO activity was also detected. The intraperitoneal injection with PB (100 mg/day/kg body weight, once a day for 2 days) or MC (20 mg/day/kg body weight, once) significantly elevated the hepatic level of AsA and the urinary excretion of AsA in rats (5-week-old males). The hepatic levels of cytochrome P-450IIB1 mRNA and cytochrome P-450IIB2 mRNA and those of cytochrome P-450IA1 mRNA and cytochrome P-450IA2 mRNA were also elevated in the rats treated with PB and MC, respectively, indicating a normal response of these animals to these compounds. However, the level of GLO mRNA and the activity of GLO in the liver tended to be slightly decreased by the administration of PB or MC, though the differences were not significant. Thus it is clear that the treatment with PB or MC stimulates the biosynthesis of AsA by increasing the activity of some enzyme(s) participating in the synthesis prior to GLO.

Animals↗

Impaired development of mammary glands in scorbutic rats unable to synthesize ascorbic acid.

The effects of ascorbic acid (AsA)-deficiency on the development of mammary glands were investigated using mutant rats (osteogenic disorder syndrome rats; ODS rats) with hereditary inability to synthesize AsA. Female ODS rats of 21 days old were castrated and divided into two groups. One group was given AsA in their drinking water, and the other was not. All the rats received a daily injection of oestradiol-17 beta and progesterone (EP) from day 28 to day 49 of age. After EP treatment, the concentrations of AsA in the mammary glands of rats not given AsA were less than one tenth of those of rats given AsA and the contents of hydroxyproline in the mammary glands of the former rats were about half of those in the latter. Furthermore, the concentration of serum prolactin in rats not given AsA was reduced to about one third of that in rats given AsA. After EP treatment, whole mounts of mammary glands showed that in rats not given AsA the development of ducts was impaired and there was extensive accumulation of endbuds. Consistent with this finding, EP injections did not increase the area of parenchyma in the mammary glands of rats not given AsA, whereas they increased it about 2-fold in rats given AsA. Moreover, after EP treatment the amount of alpha-lactalbumin was significantly less in the mammary parenchyma of rats not given AsA than in that of rats given AsA. On the other hand, AsA deficiency did not impair the response of the mammary cells to insulin or prolactin in terms of DNA synthesis and alpha-lactalbumin production. These findings indicate that AsA deficiency impaired the development of mammary glands. This effect may be partly attributable to a defect in collagen synthesis in the mammary glands and a decrease in the concentration of serum prolactin.

Animals↗

Lack of protection by ascorbic acid from lethality resulting from exposure to 1 atm O2.

The role of ascorbic acid in protecting animals against the toxic effects of exposure to 1 atm. of O2 was examined. The mean time until death resulting from exposure to one atm. O2 was not different in rats treated intraperitoneally 3 times per day with 1.5 g/kg ascorbic acid compared to saline injected controls. Exposure of rats to one atm. O2 for 48 hr did not alter ascorbic acid or non-protein thiol concentration in lung or liver compared to room air controls. Lung ascorbic acid concentration was markedly depressed in guinea pigs fed an ascorbic acid-deficient diet for 6 days prior to O2 exposure. However, the mean time until death of ascorbic acid-deficient guinea pigs did not significantly differ from those fed an ascorbic acid-supplemented diet. Exposure to one atm. O2 of guinea pigs fed an ascorbic acid-deficient diet or an ascorbic acid-supplemented diet failed to decrease the concentration of ascorbic acid or of non-protein thiol in lung. Results from this study do not support an involvement of ascorbic acid in protection from pulmonary oxygen toxicity.

Animals↗

Effect of dietary ascorbic acid on levels of serum mineral nutrients in guinea pigs.

The effect of dietary ascorbic acid on the serum mineral nutrients, Ca, Cu, Fe, K, Mg, Mn, Na and Zn in guinea pigs has been studied. Large amounts of ascorbic acid were administered to experimental animals in their drinking water. The daily ascorbic acid intake from the diet for the control animals was 10 mg/kg body weight. The mean ascorbic acid intakes for the two groups of experimental animals were 366 (37 times control) and 722 (72 times control) mg/kg body weight/day. In the ascorbic acid-treated animals, there was a significant increase in serum ascorbic acid levels in comparison with the controls. No substantial differences were observed in the body weights. The large quantities of dietary ascorbic acid did not influence serum levels of all eight minerals studied when the experimental and control values were compared using the two-tailed Student's t-test. However, serum level of copper in the guinea pigs ingesting a daily dose of 722 mg of ascorbic acid per kg body weight was slightly below control value when one-tailed Student's t-test was used.

Animals↗

Biosynthesis of ascorbic acid in germinating rapeseed cultivars.

Biosynthesis of ascorbic acid in irradiated and unirradiated germinating rapeseed cultivars was studied at ambient room temperature (20-35 degrees C). Appreciable quantities of ascorbic acid (19.8-24.1 mg/100 g) were detected in the seeds and synthesis of this vitamin increased significantly (three fold) with increasing germination time depending upon rapeseed cultivars (p < 0.05). Soaking of seeds in tap water (1:2) for 24 hours resulted in the decrease of the vitamin in each case. Among the radiation treatments (0.05-0.20 kGy), maximum amounts of ascorbic acid were found in 0.10 kGy (342.1 mg/100 g dry weight) and 0.15 kGy (113.8 mg/100 g wet weight) samples after 96 hours of germination. An overall significant linear relation (r = 0.96) was observed between vitamin biosynthesis and germination time upto 96 hours in rapeseed.

Ascorbic Acid↗

Synthesis of 2-Deoxy-2-halo-L-ascorbic Acids.

2-Iodo- and 2-bromo-2-deoxy-L-ascorbic acids (2 and 3) were prepared by facile halogenation of 2-deoxy-L-ascorbic acid (6) with NIS and NBS, respectively. Likewise, chlorination with NCS produced 2-chloro-2-deoxy-L-ascorbic acid (4), but formation of 4 was accompanied by formation of the dichloro hemiketal 9. Direct fluorination of 6 with 1-chloro-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA-BF(4)) gave only the difluoro hemiketal 10. A convenient synthesis of 2-deoxy-2-fluoro-L-ascorbic acid (5) was achieved by an indirect route. Fluorination of 2-bromo-2-deoxy-L-ascorbic acid (3) with F-TEDA-BF(4) produced the bromofluoro hemiketal 16 as a mixture of diastereoisomers. Debromination with tributyltin hydride gave 5 in good yield.

Journal Article↗