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Post mortem tissue levels of ascorbic acid in a scurvy case.

Ascorbic acid (Vitamin C) deficiency varies in degree from a mild condition scarcely recognizable, to a profound state resulting in death. In human beings, the latter condition is rarely seen except under extreme stress. One such case involving an infant is described. The analytical procedure used to determine the levels of Vitamin C in autopsy samples utilized a sensitive amino-bonded reverse-phase high-performance liquid chromatographic (HPLC) technique. Several control cases were compared to determine average normal levels.

Ascorbic Acid↗

Biosynthesis of L-ascorbic acid in plants: new pathways for an old antioxidant.

The biosynthetic pathway of L-ascorbic acid (vitamin C) in plants has been established for several years. However, recent reports describe alternative pathways, revealing a more complex picture of L-ascorbic acid biosynthesis than had been expected. GDP-L-gulose and myo-inositol are proposed as new intermediates in L-ascorbic acid biosynthesis, indicating that part of the animal pathway might also be operating in plants. Enzymatic studies on the GDP-mannose- 3',5'-epimerase and L-galactono-1,4-lactone dehydrogenase suggest that they are important regulatory steps for L-ascorbic acid biosynthesis.

Ascorbic Acid↗

Simultaneous high-performance liquid chromatographic determination of ascorbic acid and dehydroascorbic acid in biological samples.

The ascorbic acid (AA)-dehydroascorbic acid redox couple is an important component of many biological systems, and various physiological roles have been described for this vitamin. Simultaneous measurement of both AA and dehydroascorbate using high-performance liquid chromatography (HPLC) has proven difficult owing to detection problems. A simple, single-step HPLC assay for the simultaneous detection of both AA and dehydroascorbate was developed without the burden of derivatization of either compounds. This has proven to be a reliable technique and should be applicable to a wide variety of biological samples.

Animals↗

Influence of poly(ethylene glycol)-alpha-cyclodextrin complexes on stabilization and transdermal permeation of ascorbic acid.

The present study was conducted to investigate the effect of poly(ethylene glycol)-alpha-cyclodextrin (alpha-CD) complexes on stabilization and cutaneous permeation of ascorbic acid from specially prepared transdermal patches. Poly(ethylene glycol) citrate (6-armPEG) and its inclusion complex with alpha-CD were prepared and used for preparation of the transdermal patches. Duro-Tak 87-2979 was taken as an adhesive matrix in combination with ascorbic acid. A diffusion cell with an artificial membrane was used to evaluate the absorption of ascorbic acid from the patches. The influence of drug release of alpha-CD and two types of its PEG complexes (as the novel permeation enhancers) was tested. The 6-armPEG-alpha-CD complex consisting of a PEG-citric acid ester at a concentration of 0.08-0.1% (w/v) is a suitable stabilizer for ascorbic acid during UV assay. The release studies showed that the type of enhancer is important in diffusion of the drug across membrane. Furthermore, the diffusion of ascorbic acid was considerably enhanced in the presence of 6-armPEG-alpha-CD complex. Inclusion complexes of 6-armPEG with alpha-CD at a concentration of 0.08-0.1% (w/v) is a suitable stabilizer for UV method of assay. The present data suggest that 6-armPEG-alpha-CD complex is also useful in enhancing the release of ascorbic acid from the acrylic type pressure sensitive adhesives.

Administration, Cutaneous↗

Lack of maternal and developmental toxicity in mice given high doses of aluminium hydroxide and ascorbic acid during gestation.

The present study was conducted to assess if the concurrent ingestion of high doses of aluminium hydroxide and ascorbic acid might result in maternal and developmental toxicity in mice. Three groups of pregnant Swiss mice were given by gavage daily doses of aluminium hydroxide (300 mg/kg), ascorbic acid (85 mg/kg), or aluminium hydroxide (300 mg/kg) concurrent with ascorbic acid 85 (mg/kg) on gestational days 6-15. A fourth group of animals received distilled water and served as control group. Dams were killed on gestation day 18 and foetuses were examined for external, internal, and skeletal abnormalities. The reproductive data did not show embryotoxic or foetotoxic effects in any group. No gross, internal, or skeletal malformations or variations related to the different treatments were found. There were no significant differences between control and treated groups on the aluminium levels in maternal liver and bone as well as in whole body foetuses, whereas aluminium concentrations were significantly higher in placenta and kidney of dams receiving aluminium hydroxide and aluminium hydroxide plus ascorbic acid than in those from the control group. Although in this study aluminium hydroxide was given at doses higher than those usually consumed by pregnant women, no signs of maternal or developmental toxicity were observed when the compound was given alone or concurrently with high doses of ascorbic acid.

Aluminum Hydroxide↗

Ascorbic acid in bronchial asthma.

Sixteen White children with bronchial asthma were divided into two groups; one received standard anti-asthma chemoprophylaxis (SAC) and the other SAC supplemented with 1 g ascorbic acid (Redoxon) given as a single daily dose for a 6-month period. In 10 patients the effects of ascorbic acid on exercise-induced bronchoconstriction (EIB) were assessed by comparing the pre-ascorbic acid results with those obtained 2 1/2 hours after the intravenous injection of 1 g ascorbic acid. Immunological investigations performed on the two groups were assessment of polymorphonuclear leucocyte (PMNL) motility, phagocytosis and nitroblue tetrazolium reduction and measurement of secretory IgA, serum immunoglobulin and total haemolytic complement levels and levels of the components C3 and C4, alpha 1-antitrypsin, antistreptolysin O (ASO), C-reactive protein and antibodies to certain respiratory viruses. These investigations were performed before and 1, 3 and 6 months after the commencement of therapy. Radio-allergosorbent testing for sensitivity to four common allergens was carried out at the outset and after 6 months of therapy. Injection of ascorbic acid had no detectable effects on the degree of EIB. Slight but not significant immunological changes were observed in the SAC group over the 6-month study period. However, in the SAC plus ascorbic acid group significantly improved PMNL motility and decreased ASO levels and reduced (although not to a significant extent) IgE levels and titres of antibodies to the respiratory viruses were observed.

Adolescent↗

Evaluation of ascorbic acid 2-O-alpha-glucoside as vitamin C source: mode of intestinal hydrolysis and absorption following oral administration.

Ascorbic acid 2-O-alpha-glucoside (AA-2G) has been reported to have antiscorbutic activity in guinea pigs. The present experiments examined the metabolic fate of AA-2G following ingestion. Oral administration of AA-2G (96 mg) to guinea pigs resulted in a remarkable increase of ascorbic acid in various tissues as well as plasma, but intact AA-2G was detected only in plasma, but intact AA-2G was detected only in plasma and urine in small amounts. The absorption efficiency of AA-2G and ascorbic acid was further determined by using everted gut sacs of rats. Ascorbic acid released from AA-2G on the mucosal side was effectively taken up across intestinal membranes into the serosal side, whereas AA-2G poorly permeated via a passive transport system. The hydrolysis of AA-2G on the mucosal surface of everted gut was completely inhibited by an alpha-glucosidase inhibitor and the hydrolytic activity of a crude membrane extract diminished to one-forth after immunoprecipitation with the antibody specific to maltase. From these results, it is concluded that ingested AA-2G serves as a vitamin C source through the hydrolysis by intestinal membrane-bound alpha-glucosidase, mainly maltase, and the subsequent absorption of released ascorbic acid.

Administration, Oral↗

Ascorbic acid and adriamycin toxicity.

Adriamycin (ADR) is effective against a wide range of human neoplasms. However, its clinical use is compromised by serious cardiac toxicity, possibly through induction of peroxidation in cardiac lipids. Ascorbic acid, a potent antioxidant, was examined for effect in reducing ADR toxicity in mice and guinea pigs. Ascorbic acid had no effect on the antitumor activity of ADR in mice inoculated with leukemia L1210 or Ehrlich ascites carcinoma, but it significantly prolonged the life of animals treated with ADR. ADR elevated lipid peroxide levels in mouse heart, and ascorbic acid prevented the elevation. The significant prevention of ADR-induced cardiomyopathy in guinea pigs by ascorbic acid was proved by electron microscopy. Ascorbic acid and the derivatives may delay general toxicity of ADR and also prevent the cardiac toxicity. The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.

Animals↗

Ascorbic acid: a scavenger of superoxide radical.

The second order rate constant for the reaction between ascorbic acid and superoxide at pH 7.4 using the xanthine-xanthine oxidase system was estimated to be 5.4 x 10(6) M-1 sec-1. The results indicate that the efficacies of superoxide dismutase and ascorbic acid for catalyzing the decay of superoxide radical in animal tissues are similar. The significance of ascorbic acid as a scavenger of superoxide is discussed from the point of view of evolution of ascorbic acid synthesizing capacity in the terrestrial vertebrates.

Animals↗

Effects of copper, iron, and ascorbic acid on manganese availability to rats.

Four experiments were done to characterize the interactions of copper, iron, and ascorbic acid with manganese in rats. All experiments were factorially arranged Dietary Mn concentrations were less than 1 micrograms/g (Mn0) and 50 micrograms/g (Mn+). Dietary Cu was less than 1 mg/g (Cu0) and 5 micrograms/g (Cu+); dietary Fe was 10 micrograms/g (Fe10) and 140 micrograms/g (Fe140). Ascorbic acid (Asc) was not added to the diet or added at a concentration of 10 g/kg diet. Experiment 1 had two variables, Mn and Cu; in Experiment 2, the variables were Mn and Asc. In Experiment 3, the variables were Mn, Cu, and Asc; in Experiment 4, they were Mn, Cu, and Fe. Definite interactions between Mn and Cu were observed, but they tended to be less pronounced than interactions between Mn and Fe. Cu depressed absorption of 54Mn and accelerated its turnover. In addition, adequate Cu (Cu+), compared with Cu0, depressed liver, plasma, and whole blood Mn of rats. Absorption of 67Cu was higher in animals fed Mn0 diets than in those fed Mn+. Ascorbic acid depressed Mn superoxide dismutase activity and increased Cu superoxide dismutase activity in the heart. The addition of ascorbic acid to the diet did not affect Mn concentration in the liver or blood. Absorption of 54Mn was depressed in rats fed Fe140 compared with those fed Fe10. Interactions among Fe, Cu, and Mn resulted in a tendency for Mn superoxide dismutase activity to be lower in rats fed Fe140 than in rats fed Fe10. Within the physiologic range of dietary concentrations, Mn and Cu have opposite effects on many factors that tend to balance one another. The effects of ascorbic acid on Mn metabolism are much less pronounced than effects of dietary Cu, which in turn affects Mn metabolism less than does Fe.

Absorption↗

Ascorbic acid and intestinal metaplasia in the stomach: a prospective, randomized study.

BACKGROUND: Intestinal type metaplasia plays a role in intestinal type gastric carcinoma development. Ascorbic acid demonstrates a protective effect against gastric carcinogenesis, due to its ability to inactivate oxygen free-radicals as well as its nitrite-scavenging effects. AIM: To assess whether long-term ascorbic acid administration following Helicobacter pylori eradication could affect intestinal metaplasia regression in the stomach. METHODS: Sixty-five patients were included in the study. The inclusion criterion was the presence of intestinal metaplasia on the gastric mucosa after H. pylori eradication. An upper gastrointestinal endoscopy was performed and 3 biopsy specimens were taken in the antrum, 3 in the gastric body, and 2 in the incisura angularis. Patients were randomized to receive 500 mg of ascorbic acid o.d., after lunch (32 patients) for 6 months or no treatment (33 patients). All patients underwent to endoscopic control at the end of the 6 months. RESULTS: H. pylori infection recurrence was detected in 6 (9.4%) patients (three from each group), and these patients were excluded from further analysis. We were unable to find evidence of intestinal metaplasia in any biopsied site of the gastric mucosa in 9/29 (31%) patients from the ascorbic acid group and in 1/29 (3.4%) of the patients from the control group (P=0.006). Moreover, a further six (20.7%) patients from the ascorbic acid group presenting chronic inactive pangastritis with widespread intestinal metaplasia at entry, showed less extensive antritis with intestinal metaplasia at control, whilst a similar finding was only seen in one patient from the control group (P=0.051). CONCLUSION: The administration of ascorbic acid significantly helps to resolve intestinal metaplasia of the gastric mucosa following H. pylori eradication, and its use as a chemoprevention treatment should be considered.

Adult↗

Both HDL3 and HDL2 exert a powerful anti-oxidative and protective effect against acceleration of oxidative modification of LDL by ascorbic acid.

The objective of the present study was to establish whether high-density lipoprotein 3 (HDL3) or high-density lipoprotein 2 (HDL2) might show an anti-oxidative effect on the acceleration of the oxidative modification of low-density lipoprotein (LDL) by ascorbic acid from measurement of the agarose gel electrophoretic mobility of LDL. LDL was incubated without adding transitional-metal ions for 48 or 96 h in phosphate-buffered saline (PBS) alone, with ascorbic acid (20 microg/mL), or with both ascorbic acid (20 microg/mL) and HDL3 (200 microg protein/mL). The LDL autoxidation occurred in PBS alone. Although ascorbic acid significantly suppressed oxidative modification of LDL after incubation for 48 h, the opposite was true after 96 h. However, since the anti-oxidative ability of HDL2 shows a weaker tendency than that of HDL3, both HDL3 and HDL2 significantly inhibited this acceleration of oxidative modification of LDL by ascorbic acid as assessed by electrophoretic mobility. If there is an augmented oxidative modification of LDL due to ascorbic acid in vivo, HDL3 or HDL2 may thus have an important role in inhibiting this ascorbic acid-accelerated oxidation of LDL.

Antioxidants↗

Characterization of ascorbic acid uptake by isolated rat kidney cells.

Isolated kidney cells accumulated L[1-14C]ascorbic acid in a time-dependent manner and reached a steady state after 15 min at 37 degrees C. Initial velocity for uptake was over 300 pmol/mg protein per min when cells were separated from the bathing solution using a density gradient established during centrifugation. The uptake process was saturable with an apparent concentration at half maximal uptake of 36 mumols/L. Ascorbate uptake was reduced by metabolic inhibitors and was temperature dependent. Although ascorbic acid is an acid anion at pH 7.4, uptake did not appear to be inhibited by other acid anions such as p-aminohippurate and probenecid; however, involvement of the ion gradient established by Na+, H(+)-adenosine triphosphatase could not be confirmed. Replacing the sodium ion with other monovalent ions reduced the accumulation of ascorbate significantly. Isoascorbic and dehydroascorbic acids inhibited ascorbate uptake (34 and 13 mmol/L, respectively), whereas high concentrations of glucose showed some stimulation. These findings indicated that ascorbic acid is reabsorbed by the kidney in a sodium-dependent active transport process that is not common to other acid anions and has some specificity for the ascorbic acid structure.

Adenosine Triphosphate↗

Lack of effect of ascorbic acid on serum lipoprotein concentrations in patients with hypertriglyceridaemia.

Previous studies on the possible effects of ascorbic acid on lowering serum triglycerides have given conflicting results. We have treated 9 patients with stable type IV hyperlipoproteinaemia despite adequate dietary treatment with placebo for 1 month, followed by ascorbic acid at 1 g twice daily for another month. Ascorbic acid did not change either triglyceride or cholesterol in whole serum or in any lipoprotein fraction. We conclude that treatment for 1 month with 2 g of ascorbic acid per day has no effects on lowering triglyceride concentrations.

Adult↗

Metabolism of hydrogen peroxide in Euglena gracilis Z by L-ascorbic acid peroxidase.

Euglena gracilis was found to contain a peroxidase that specifically require L-ascorbic acid as the natural electron donor in the cytosol. The presence of an oxidation-reduction system metabolizing L-ascorbic acid was demonstrated in Euglena cells. Oxidation of L-ascorbic acid by the peroxidase, and the absence of ascorbic acid oxidase activity, suggests that the system functions to remove H2O2 in E. gracilis, which lacks catalase.

Ascorbate Peroxidases↗

Acute effect of ascorbic acid on fibrinolytic activity.

The acute effect of 1 g oral ascorbic acid on serum fibrinolytic activity was studied in 40 adult males. In Group I (healthy adults) administration of ascorbic acid raised the serum level by about 71%, while the fibrinolytic activity increased to a peak of 137% at 6 h. In patients with CAD (Group II) an essentially similar increase in FA was observed. In Group III, simultaneous administration of ascorbic acid with 100 g fat effectively prevented a fall in fibrinolytic activity and actually raised it by 64% above the fasting level.

Adult↗

Ascorbic acid metabolism in diabetes mellitus.

In contrast to normal subjects diabetic patients and very low plasma ascorbic acid and significantly high (p less than 0.001) dehydroascorbic acid irrespective of age, sex, duration of the disease, type of treatment, and glycemic control. However, there was no significant difference between the mean leukocyte ascorbate concentrations of the two populations. The in vitro rates of dehydroascorbate reduction in the hemolysate and the erythrocyte reduced glutathione levels and the glucose-6-phosphate dehydrogenase activities, which regulate the dehydroascorbate reduction, were similar in normal and diabetic subjects. The turnover of ascorbic acid was higher in the diabetics than that in the normal volunteers. Experiments with diabetic rats indicated that the increased turnover of ascorbic acid was probably due to increased oxidation of ascorbate to dehydroascorbate in tissue mitochondria. Ascorbic acid supplementation at a dose of 500 mg per day for a brief period of 15 days resulted in an increase in the plasma ascorbate level temporarily, but it did not lower the blood glucose level of the diabetic patients.

Adolescent↗

Ascorbic acid stimulates DOPA synthesis and tyrosine hydroxylase gene expression in the human neuroblastoma cell line SK-N-SH.

Ascorbic acid is well known to induce noradrenaline synthesis in sympathetic nervous cells. In a series of experiments we found that incubation of the neuroblastoma cell line SK-N-SH with ascorbic acid (100-500 microM) for 2 h results in a significantly enhanced synthesis of 3,4-dihydroxyphenylalanine (DOPA) and dopamine. Additionally, cDNA-polymerase chain reaction (cDNA-PCR) analysis of relative mRNA levels corresponding to the enzymes involved in catecholamine synthesis revealed a 3-fold increase of tyrosine hydroxylase gene expression after 5 days of incubation with ascorbic acid (200 microM), whereas expression of dopamine-beta-hydroxylase was found to be unaltered. In summary the data give evidence that ascorbic acid leads to enhanced DOPA production in SK-N-SH cells by two different mechanisms: at the metabolic level after short-term incubation and by increasing the tyrosine hydroxylase gene expression after long-term incubation. Based on these data we suppose that enhancement of DOPA synthesis by ascorbic acid may be useful in the treatment of early Parkinson's disease.

Ascorbic Acid↗