A biochemical abnormality in schizophrenia involving ascorbic acid.
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Ascorbic Acid↗
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[Vitamin C (ascorbic acid)].
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Ascorbic Acid↗
Effect of ascorbic acid supplementation on the immune response of chickens vaccinated and challenged with infectious bursal disease virus.
One-day-old chickens were divided into two groups and reared under similar conditions. One group was fed a diet supplemented with 1000ppm ascorbic acid and the other group was fed an identical diet, but not supplemented with ascorbic acid. Both groups were vaccinated against infectious bursal disease (IBD) at 7 days of age and challenged orally with 4x10(5) of 50% embryo-lethal-dose IBDV 14 days later. The number of anti-IBDV antibody secreting cells, production of interleukin-2 (IL-2) by splenocytes, number of CD4(+), CD8(+) and IgM(+) cells in spleen and IgM(+) cells in bursa of Fabricius were compared between the two groups at 7 days (prior to vaccination), 21 days (14 days post-vaccination and prior to challenge) and 31 days (10 days post-challenge) of age. The number of CD8(+) in spleen at 7 days of age and IgM(+) cells in bursa at 7, 21 and 31 days of age were significantly higher in ascorbic acid supplemented group (P<0.05). Production of IL-2 by splenocytes was higher as indicated by higher stimulation indices in ascorbic acid supplemented group. The number of anti-IBDV IgG antibody secreting cells in spleen at 21 and 31 days of age were significantly higher in ascorbic acid supplemented group (P<0.05). Dietary supplementation of ascorbic acid may ameliorate the immunosuppression caused by IBDV vaccination and improve humoral and cellular immune responses.
Animals↗
Effects of ascorbic acid on levels of fibronectin, laminin and collagen type 1 in bovine trabecular meshwork in organ culture.
PURPOSE: Fibronectin, laminin and collagen type I are important extracellular matrix products of trabecular meshwork cells. This study was performed to examine the effects of ascorbic acid, a significant component in the aqueous humor, on the levels of these proteins in trabecular meshwork cells maintained in organ culture. METHODS: The anterior segment of freshly enucleated bovine eyes was perfused in a modified organ culture system. Three cultures were set up simultaneously. One received serum-free medium containing 100 micrograms/ml of ascorbic acid, one received 250 micrograms/ml of ascorbic acid and one served as a control. After 72 h, the tissues were processed for paraffin sections and immunostaining was conducted using an avidin-biotin-peroxidase complex method. Western blot and dot blot assays were performed on tissue extracts. RESULTS: Compared with the controls, the staining for fibronectin and laminin was markedly enhanced in trabecular meshwork tissues treated with both concentrations of ascorbic acid. Increased collagen type I production by trabecular meshwork cells was also demonstrated in the presence of ascorbic acid. Western blot and dot blot results confirmed the immunostaining findings. CONCLUSIONS: Ascorbic acid promotes production of fibronectin, laminin and collagen type I by trabecular meshwork cells. The organ culture results are consistent with those obtained previously from tissue culture studies.
Animals↗
Evaluation of the effect of ascorbic acid treatment on wound healing in mice exposed to different doses of fractionated gamma radiation.
Alteration of the radiation-induced changes in wound contraction, collagen synthesis and wound histology by ascorbic acid was studied in mice exposed to 10, 16 and 20 Gy of fractionated (2 Gy/fraction) gamma radiation. The animals were given double-distilled water or ascorbic acid daily before exposure to 2 Gy/day of fractionated irradiation. A full-thickness skin wound was created on the dorsum of the irradiated mice, and the progression of wound contraction and collagen synthesis were examined and histological evaluations were carried out at various times after wounding. Irradiation caused a dose-dependent delay in wound contraction, and pretreatment with ascorbic acid resulted in a significant increase in wound contraction. The greatest increase in wound contraction was observed 6 and 9 days after wounding in both groups. Pretreatment with ascorbic acid augmented the synthesis of collagen significantly as revealed by an increase in hydroxyproline content. The collagen deposition and fibroblast and vasculature densities declined in a dose-dependent manner in groups receiving radiation alone as indicated by histological evaluation. Pretreatment with ascorbic acid ameliorated the observed effect significantly. These studies demonstrate that pretreatment with ascorbic acid resulted in a significant reduction of radiation-induced delay in wound healing as shown by earlier wound closure and increased collagen content and fibroblast and vascular densities.
Animals↗
Iron(II) phthalocyanine-modified carbon-paste electrode for potentiometric detection of ascorbic acid.
A chemically modified electrode constructed by incorporating iron(II) phthalocyanine [Fe(II)Pc] into carbon-paste matrix was used as a sensitive potentiometric sensor for detection of ascorbic acid. The resulting electrode exhibits catalytic properties for the electrooxidation of ascorbic acid, and lowers the overpotential for the oxidation of this compound. The faster rate of electron transfer results in a near-Nernstian behavior of the modified electrode, and makes it a suitable potentiometric sensor for detection of ascorbic acid. A linear response in concentration range from 10(-6) to 10(-2) M (0.18--1800 microg ml(-1)) was obtained with a detection limit of 5 x 10(-7) M for the potentiometric detection of ascorbic acid. The modified electrode was used for the determination of ascorbic acid in vitamin preparations. The recovery was 97.2--102.4% for the vitamin added to the preparations with a relative standard deviation of less than 5%. The modified electrode exhibited a fast response time (<10 s),had good stability, and had an extended lifetime.
Ascorbic Acid↗
Beta-carotene and protein oxidation: effects of ascorbic acid and alpha-tocopherol.
The effect of beta-carotene on protein oxidation was examined under different oxygen (O(2)) tensions and with other antioxidants: alpha-tocopherol, ascorbic acid, and mixtures of antioxidants. Human serum albumin (HSA) was incubated with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) to induce protein oxidation (carbonyl formation), under 15, 150, and 760 torr of O(2) tension. Antioxidant activity was related to O(2) tension, antioxidant concentrations and interaction between mixtures of antioxidants: (1) Under 15 torr of O(2), incubating HSA with AAPH, 1. 6 microM beta-carotene, 80 microM alpha-tocopherol, 160 microM ascorbic acid, and mixtures (0.1 microM beta-carotene, 5.0 microM alpha-tocopherol and 10 microM ascorbic acid) resulted in 24, 29, 39, and 44% reduction of carbonyl formation, respectively. (2) Under 150 torr of O(2) tension, the antioxidant effect of beta-carotene was decreased by 4% but increasing O(2) tension did not diminish the antioxidant effects of alpha-tocopherol, ascorbic acid, or antioxidant mixtures. (3). Under 760 torr of O(2) tension, adding 1. 6 microM beta-carotene resulted in 26% more carbonyl formation. (4) Under 760 torr of O(2) tension, the antioxidant effect of ascorbic acid was decreased 32% compared to what was observed at 150 torr of O(2) tension. Changes in O(2) tension had no effect on the antioxidant effect of alpha-tocopherol. The mixture of antioxidants inhibited carbonyl formation by 37% and was 7% less effective than that of 15 and 150 torr of O(2) tension. High concentration of beta-carotene produces more protein oxidation in the presence of high O(2) tension by a prooxidant mechanism. Mixtures of beta-carotene, alpha-tocopherol, and ascorbic acid provided better protective effects on protein oxidation than any single compound.
Amidines↗
Further investigations on the role of ascorbic acid in stratum corneum lipid models after UV exposure.
This study is the continuation of our research into vitamin C and its possible effects on human skin after topical administration. The effects of ascorbic acid, iron ions and UV irradiation on stratum corneum lipid models were investigated. The lipid models used were: a simple system (linolenic acid dispersion), a complex system (liposomes consisting of dipalmitoylphosphatidylcholine, cholesterol and linolenic acid) and complex systems with additionally incorporated ceramides (types III and IV). The lipid peroxidation was quantified by the thiobarbituric acid assay. A human adult low-calcium high-temperature (HaCaT) keratinocytes cell culture was used as a second in-vitro model. The amount of intracellular peroxides was determined by measuring the fluorescence intensity using the dihydrorhodamine 123 assay. Electron paramagnetic resonance spectroscopy was used to study the influence of ascorbic acid and iron ions on the signal intensity of 5-doxylstearic acid during UV exposure. Ascorbic acid showed prooxidative properties in the thiobarbituric acid assay whereas cell protection was measured in the HaCaT keratinocytes experiments. Electron paramagnetic resonance investigations revealed different extents of free radical production generated by iron ions, ascorbic acid and UV irradiation. In evaluating the results from this study new aspects of the mechanism of lipid damage caused by these three factors were suggested, transcending the simple redox behaviour of ascorbic acid.
Ascorbic Acid↗
The novel C-5 aryl, alkenyl, and alkynyl substituted uracil derivatives of L-ascorbic acid: synthesis, cytostatic, and antiviral activity evaluations.
The novel C-5 substituted uracil derivatives of l-ascorbic acid were synthesized by coupling of 5-iodouracil-4,5-didehydro-5,6-dideoxy-l-ascorbic acid with unsaturated stannanes under Stille reaction conditions. The new compounds were evaluated for their antitumoral and antiviral activities. Among all compounds evaluated the 5-propynyl substituted uracil derivative of l-ascorbic acid (7) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC(50): 0.2-0.78 microM). However, this compound was also cytotoxic to human normal fibroblasts WI 38. The 5-(phenylethynyl)uracil-2,3-di-O-benzylated l-ascorbic acid derivative (4) exhibited an albeit slight (IC(50): 55-108 microM), but selective inhibitory effect toward all tumor cell lines except for cervical carcinoma (HeLa), pancreatic carcinoma (MiaPaCa-2), laryngeal carcinoma (Hep-2), and colon carcinoma (SW 620), and no cytotoxicity to normal human fibroblast (WI 38). Compound 7 showed some, not highly specific, inhibitory potential against vesicular stomatitis virus, Coxsackie B4 virus, and Sindbis viruses (EC(50): 1.6 microM).
Animals↗
The effect of water, ascorbic acid, and cranberry derived supplementation on human urine and uropathogen adhesion to silicone rubber.
In this study, urine was collected from groups of volunteers following the consumption of water, ascorbic acid, or cranberry supplements. Only ascorbic acid intake consistently produced acidic urine. Photospectroscopy data indicated that increased water consumption produced urine with lower protein content. Surface tension measurements of the collected urine showed that both water and cranberry supplementation consistently produced urine with surface tensions higher than the control or urine collected following ascorbic acid intake. These urine samples were also employed to study uropathogen adhesion to silicone rubber in a parallel plate flow chamber. Urine obtained after ascorbic acid or cranberry supplementation reduced the initial deposition rates and numbers of adherent Escherichia coli and Enterococcus faecalis, but not Pseudomonas aeruginosa, Staphylococcus epidermidis, or Candida albicans. Conversely, urine obtained from subjects with increased water intake vastly increased the initial deposition rates and numbers of adherent E. coli and E. faecalis (P < 0.05).
Adult↗
The relationship between low leucocyte ascorbic-acid levels and tyrosine metabolism in the elderly.
Twenty-seven elderly men aged 69-94 years had tyrosine tolerance tests measured before and after receiving ascorbic acid 1 g daily for four days. There was a significant rise in the fasting and half-hourly mean plasma tyrosine levels after ascorbic acid administration in those subjects with an initial leucocyte ascorbic-acid level (LAA) below 15 micrograms/10(8) w.c.c. The peak of the tyrosine tolerance curve was also advanced following administration of ascorbic acid in those subjects with an initial LAA below 15 micrograms/10(8) w.c.c. A further ten elderly men aged 73-89 years had simultaneous measurements of the circadian rhythms of LAA, plasma cortisol and plasma tyrosine levels before and after receiving ascorbic acid 1 g daily for four days. All ten subjects showed a peak LAA level at 5 p.m. when saturated with vitamin C but there was no significant correlation between plasma cortisol changes and plasma tyrosine changes. Possible explanations for the results are discussed.
Aged↗
Effect of ascorbic acid on protein synthesis and collagen hydroxylation in continuous flow organ cultures of adult mouse periodontal tissues.
A continuous flow organ culture system (CFCS) was used to determine the effect of ascorbic acid on the synthesis of collagen and noncollagenous protein by bone of the alveolar process and periodontal ligament in organ cultures of adult mouse periodontium. For the last 24 h of 2 day cultures, 5 microCi/ml 3H-proline was added to the medium. Highly purified collagenase was used to separate the collagenous and noncollagenous proteins and the incorporation of isotope into each fraction measured. Collage synthesized in the presence of less than 10 micrograms/ml ascorbic acid was found to be highly under-hydroxylated (pro:hypro ap. acts. 2.3-3.1) in both tissues. When the ascorbic acid levels were between 25 and 100 micrograms/ml, the synthesis of collagenous proteins was selectively stimulated and hydroxylation significantly improved (pro:hypro sp. acts 1.72-1.89). The effect of ascorbic acid was not related to tissue viability since tissues cultured initially in the absence of ascorbic acid were able to recover completely when compared to controls given ascorbic acid continuously. The proportion of radioactivity in collagen and noncollagenous protein, collagen hydroxylation, and percentage of collagen synthesized as type III (av.23%) in bone of the alveolar process was similar to that found in vivo. However, in the periodontal ligament in vitro the proportion of noncollagenous protein synthesized was increased from 70% to 87% and the percentage of type III collagen increased from 14% to 26% compared to in vivo results.
Alveolar Process↗
Ascorbic acid status in iron-deficiency anaemia.
Leucocyte ascorbic acid concentration declines with age. Patients with iron-deficiency anaemia have higher concentrations than normal while those with iron overload have a reduced concentration. It is suggested that these phenomena may be a result of reduced ascorbate catabolism in iron-deficiency anaemia and they provide support for the suggestion that the amount of iron in the tissues may be an important factor in determining ascorbic acid utilization.
Adolescent↗
Dietary ascorbic acid and resistance to experimental renal candidiasis.
Guinea pigs were maintained for various periods of time on low (0.5 mg/day), intermediate (20 mg/day), or high (100 and 500 mg/day) levels of dietary ascorbic acid. Animals in each experimental group were challenged with Candida albicans via cardiac injection, and the course of infection in the kidneys was assessed. The results show that the animals receiving only 0.5 mg of ascorbic acid per day were significantly more susceptible to the infection than animals maintained on any higher level of dietary ascorbic acid. The greater susceptibility of the guinea pigs in the 0.5-mg level group was evident, however, only during "early" stages of the infection (until about day 3). Guinea pigs receiving high levels of dietary ascorbic acid were no more resistant at any time after infection, or with any challenge dose, than those receiving an intermediate dietary level. Although these data suggest that vitamin C may be involved in resistance to candidiasis, tissue levels of ascorbic acid do not change significantly with time after infection. These results indicate that low levels of dietary ascorbic acid increase susceptibility to candidiasis, yet high (or "megadose") levels of dietary vitamin C do not show any effect on resistance to this microorganism.
Animals↗
Uptake of ascorbic acid by human neutrophils.
Human neutrophils produce bacterial oxidants that could have a damaging effect on the neutrophils themselves. For protection, neutrophils acquire a high (10-20 mmol/L) level of intracellular ascorbic acid by oxidizing extracellular ascorbic acid to dehydroascorbic acid, rapidly taking up the dehydroascorbic acid and re-reducing it to ascorbic acid.
Ascorbic Acid↗
Ascorbic acid mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for anticancer properties.
Several decades back ascorbic acid was proposed as an effective anticancer agent. However, this idea remained controversial and the mechanism of action unclear. In this paper, we show that ascorbic acid at a concentration reported to be achievable through high doses of oral consumption is capable of cytotoxic action against normal cells. Several antioxidants of both animal as well as plant origin including ascorbic acid also possess prooxidant properties. Copper is an essential component of chromatin and can take part in redox reactions. Previously we have proposed a mechanism for the cytotoxic action of plant antioxidants against cancer cells that involves mobilization of endogenous copper ions and the consequent generation of reactive oxygen species. Using human peripheral lymphocytes and Comet assay we show here that ascorbic acid is able to cause oxidative DNA breakage in normal cells at a concentration of 100-200 microM. Neocuproine, a Cu(I) specific sequestering agent inhibited DNA breakage in a dose dependent manner indicating that Cu(I) is an intermediate in the DNA cleavage reaction. The results are in support of our above hypothesis that involves events that lead to a prooxidant action by antioxidants. The results would support the idea that even a plasma concentration of around 200 microM. would be sufficient to cause pharmacological tumor cell death particularly when copper levels are elevated. This would account for the observation of several decades back by Pauling and co-workers where oral doses of ascorbic acid in gram quantities were found to be effective in treating some cancers.
Antineoplastic Agents↗
Inhibition of lipid peroxidation in low-density lipoprotein by the flavonoid myrigalone B and ascorbic acid.
Lipid peroxidation in human LDL (0.05 mg protein/mL) incubated with Cu(2+)-ions (5 microM) in vitro was dose-dependently inhibited by the flavonoid myrigalone B (MyB) and by ascorbic acid. MyB at 6 microM increased the oxidation lag time by 135 +/- 24 min (approximately 5-fold compared to controls) and reduced the maximum oxidation rate by 46 +/- 5%. Ascorbic acid, at 9 microM, increased the lag time by 179 +/- 29 min (6-fold compared to controls) but did not affect the maximum oxidation rate. The increase in lag time induced by MyB was enhanced in the presence of ascorbic acid. Their effects were additive, except when both were present at the highest concentration tested, when a significant potentiation, giving an increase in lag time of approximately 2 hr more than the sum of separate effects, occurred. Concentration-time curves for MyB in the absence and presence of ascorbic acid showed that the vitamin protected MyB against deterioration during incubation, and indicated that the net consumption of MyB in the oxidation process was reduced. No differences were observed when ordinary ascorbic acid and Ester-C, a commercial vitamin C product, were compared. In conclusion, MyB and ascorbic acid seem to interact in a way that further improves the antioxidant status of the LDL particle relative to each substance separately.
Ascorbic Acid↗
Influence of ascorbic acid on the mutagenicity of N-methyl-N-nitrosoguanidine and nitrofurans studied by SOS chromotest.
Mutagenicity inhibition of MNNG*, NFAA* as well as of nitrovin by ascorbic acid was observed. The influence of ascorbic acid on these compounds was parallelly studied also by spectroscopy. Mutagenicity inhibition was characterized by SOS chromotest. Inhibition degree was evaluated quantitatively introducing the coefficient of inhibition. The influence of ascorbic acid was expressed most markedly in MNNG. It has been found that the decrease of mutagenicity should be mainly caused by acceleration of MNNG decomposition by ascorbic acid.
Acrylates↗