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Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes.

Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes. We studied the hemodynamic effects of chronic oral supplementation in this condition. Thirty patients, 45 to 70 years of age, with type 2 diabetes, were randomly assigned in a double-blind manner to receive 500 mg ascorbic acid daily by mouth or placebo. Patients were studied at baseline and after 4 weeks of assigned treatment. The central aortic augmentation index (AgIx) and the time to wave reflection (Tr) were derived from radial artery pulse wave analysis data. AgIx and Tr were used as measures of systemic arterial stiffness and aortic stiffness, respectively. Ascorbic acid decreased brachial systolic blood pressure from 142.1+/-12.6 (SD) to 132.3+/-12.1 mm Hg (difference [95% CI] 9.9 [4.7, 15.0]; P<0.01), brachial diastolic pressure from 83.9+/-4.8 to 79.5+/-6.0 mm Hg (4.4 [1.8, 7.0]; P<0.01), and AgIx from 26.8+/-5.5% to 22.5+/-6.8% (4.3 [1.5, 7.1]; P<0.01). Tr increased from 137.1+/-12.6 to 143.4+/-9.2 ms (-6.3 [-10.1, -2.5]; P<0.01). Placebo had no hemodynamic effects, and this difference between treatments was significant (P<0.01 for blood pressure and Tr, P=0.03 for AgIx). We have therefore shown that after 1 month, oral ascorbic acid lowered arterial blood pressure and improved arterial stiffness in patients with type 2 diabetes. As strict control of blood pressure reduces cardiovascular risk in diabetes, ascorbic acid supplementation may potentially be a useful and inexpensive adjunctive therapy. Larger and longer studies now need to be performed.

Administration, Oral↗

Evidence for ascorbic acid transport system in rat brain capillaries.

Although ascorbic acid (AA) crosses the choroid plexus and may enter the brain at an appreciable rate, it is not clearly established that there exist transport system(s) carrying this vitamin from blood into the brain cells across the brain capillaries. Thus the rate of its uptake by choroid plexus and cerebral capillaries were evaluated in vitro in this study. Choroid plexus and brain capillaries were isolated from two-month-old male Sprague-Dawley rats. Time course of AA incorporation in micro vessels and choroid plexus was studied up to 30 min. After stopping the incorporation with the excess of cold isotonic saline, micro vessels were filtered and sonicated. The intracellular incorporated AA radioactivity was measured by liquid scintillation counting. AA uptake by micro vessel was tested for Na+-dependence and saturability. The time course studies showed linear increase in total uptake and accumulation of AA by choroid plexus and endothelial cells up to 30 min. Treatment with oubain or replacement with sodium chloride showed that uptake is an Na+- independent process. Transport of AA to cerebrospinal fluid and brain was also shown to be readily saturated by increasing the level of cold AA. These results document that the brain capillary endothelial cells are able to transport and accumulate AA, and may have a critical role in the homeostasis and regulation of cerebral ascorbic acid concentration.

Animals↗

l-Ascorbic Acid Biosynthesis in Ochromonas danica.

Ochromonas danica Pringsheim, a freshwater chrysomonad, converts d-glucose into l-ascorbic acid over a metabolic pathway that ;inverts' the carbon chain of the sugar. In this respect, l-ascorbic acid formation resembles that found in ascorbic acid-synthesizing animals. It differs from this process in that d-galacturonate and l-galactono-1,4-lactone, rather than d-glucuronate and l-gulono-1,4-lactone, enhance production of ascorbic acid and repress the incorporation of (14)C from d-[1-(14)C]glucose into ascorbic acid.

Journal Article↗

Acute effect of ascorbic acid infusion on carbohydrate tolerance.

Large doses (1 to 2g/3 hr) of ascorbic acid were administered intravenously to normal weight and obese, nondiabetic subjects. Glucose tolerance and fasting plasma glucose levels were unaffected, despite a 3- to 8-fold rise in plasma concentrations of the vitamin. Infusion of ascorbic acid did not alter fasting serum insulin levels in normal subjects, but was associated with lower concentrations of hormone during an intravenous glucose tolerance test. Plasma glucose, serum insulin, growth hormone, and glucagon levels in obese subjects remained unchanged during the ascorbic acid infusion.

Ascorbic Acid↗

Ascorbic acid reduces the endotoxin-induced lung injury in awake sheep.

Our aim was to investigate whether ascorbic acid can reduce reactive oxygen metabolite-mediated acute lung injury. The effects of intravenous administration of Escherichia coli endotoxin were studied, with and without ascorbic acid infusion, on haemodynamics, lung lymph flow, cardio-respiratory and neutrophil function in chronically instrumented sheep. Paired experiments were performed on eight sheep in which they received either endotoxin alone (0.5 micrograms kg-1 b.w.) (ET group) or in combination with an ascorbic acid infusion (1 g kg-1 b.w. bolus injection followed by 0.2 g kg-1 h-1 continuous infusion) ET + ASC group) in random order. Four of the animals also received ascorbic acid alone (ASC group). As a result, for the ET + ASC group a general and mostly significant improvement (P < 0.05) in the early hypertensive phase (0-60 min, P values) and in the late permeability phase (2-4 h, *P values) of cardiorespiratory function (mean artery pressure: P/*P = 0.283/0.049; mean pulmonary artery pressure: P/*P = 0.0001/0.0001; mean pulmonary artery wedge pressure: P/*P = 0.012/0.001; right ventricular stroke work index: P/*P = 0.02/0.0001; cardiac index: P/*P = 0.797/0.755; arterial oxygen saturation: P/*P = 0.0059/0.01; arterial-venous difference of oxygen tension: P/*P = 0.011/0.0005), oxygen consumption: P/*P = 0.013/0.035, lung lymph flow: P/*P = 0.562/0.012, lymph/plasma protein ratio: P/*P = 0.304/0.008 and protein clearance: P/*P = 0.56/0.05 was observed in comparison with the ET group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of ascorbic acid on proliferation and collagen synthesis in relation to the donor age of human dermal fibroblasts.

Several events are associated with cellular aging: alterations in the extracellular matrix, loss of the cell's proliferative capacity, and decreased responsiveness to growth factors. In skin, a major component of the extracellular matrix is collagen; an important regulator of collagen synthesis is ascorbic acid, which may also have growth factor-like properties. To investigate the relationship of the extracellular matrix and proliferative capacity to aging, we examined the effects of ascorbic acid on cell proliferation and collagen expression in dermal fibroblasts from donors of two age classes, newborn (3-8 d old) and elderly (78-93 years old). In the absence of ascorbic acid (control) proliferative capacities were inversely related to age; newborn cell lines proliferated faster and reached greater densities than elderly cell lines. However, in the presence of ascorbic acid both newborn and elderly cells proliferated at a faster rate and reached higher densities than controls. To determine whether there are age-related differences in extracellular matrix production and ascorbic acid responsiveness we examined and found that collagen biosynthesis (collagenase-digestible protein) was inversely related to age, but the stimulation by ascorbic acid appeared age independent. The increase in collagen synthesis was reflected by coordinate increases in steady-state pro alpha 1(I) and pro alpha 1(III) collagen mRNAs, suggesting a pretranslational mechanism. Ascorbic acid appears capable of overcoming the reduced proliferative capacity of elderly dermal fibroblasts, as well as increasing collagen synthesis in elderly cells by similar degrees as in newborn cells even though basal levels of collagen synthesis are age dependent.

Aged↗

Inhibitory effect of ascorbic acid post-treatment on radiation-induced chromosomal damage in human lymphocytes in vitro.

In the present study, the effect of exposure to ascorbic acid (vitamin C) after gamma-ray-induced chromosomal damage in cultured human lymphocytes was examined to explore the mechanism by which this antioxidant vitamin protects irradiated cells Non-irradiated lymphocytes were exposed to increasing concentrations of ascorbic acid (1-100 micro g/ml) and DNA damage was estimated using chromosomal aberration analysis and the comet assay. The results showed that ascorbic acid did not influence the frequency of chromosomal aberrations in non-irradiated cells, except at the highest concentration (20 micro g/ml), which induced breakage-type chromosomal aberrations. Vitamin C at the concentration of 50 micro g/ml caused DNA damage detected by the comet assay. A significant (34%) decrease in the frequency of chromosomal aberrations was observed in lymphocytes exposed to gamma-radiation and then cultured in the presence of ascorbic acid (1 micro g/ml). The removal of DNA breaks in cells exposed to 2 Gy of gamma-radiation was accelerated in the presence of ascorbic acid as determined by the comet assay, suggesting that it may stimulate DNA repair processes.

Antioxidants↗

Ascorbic acid and pyridoxine in experimental anaphylaxis.

Two vitamins, ascorbic acid (AA) and pyridoxine have been suggested by others as useful drugs for the treatment of bronchial asthma, although the views concerning AA or controversial. We have tested both vitamins in some models of histamine release and experimental anaphylaxis. AA does not inhibit mast cell degranulation induced by phospholipase A and histamine release from isolated rat mast cells induced by compound 48/80 or antigen (egg albumin). On the contrary, in the latter tests pyridoxine exerts inhibition in a range of concentrations from 10(-3)-10(-2) M. We conclude: 1. There is no experimental basis for considering ascorbic acid as a prophylactic antiasthmatic drug as is disodium cromoglycate. 2. Pyridoxine must receive additional basic and clinical investigations in this field.

Anaphylaxis↗

Ascorbic acid synthesis in certain guinea pigs.

Three guinea pigs fed a vitamin C-free diet manifested no symptoms of scurvy even after 4-8 months, normally increased in body weight and excreted quantities of ascorbic acid in urine far exceeding the total body pool of ascorbic acid. The course of healing subsequent to experimental trauma in one of these animals proved to be entirely normal and vitamin C concentration in its liver after 8 months of a scorbutogenic regimen was found to be more than twice that in guinea pigs with a daily intake of 10 mg ascorbic acid. It is evident that certain guinea pigs are capable to synthesize ascorbic acid that fully covers the needs of the organism. However, the freqency of occurence of such guinea pigs appears to be extremely small.

Animals↗

Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults.

Maximal aerobic capacity (Vo(2max)) decreases progressively with age, primarily because of a reduction in maximal cardiac output (Q(max)). This age-associated decline in Vo(2max) may be partially mediated by the development of oxidative stress that can suppress beta-adrenergic-receptor responsiveness and, consequently, reduce Q(max). To test this hypothesis, Vo(2max) (indirect calorimetry) and Q(max) (open-circuit acetylene breathing) were determined in 12 young (23 +/- 1 yr, mean +/- SE) and 10 older (61 +/- 1 yr) adults following systemic infusion of either saline (control) and/or the powerful antioxidant ascorbic acid (acute: bolus 0.06; drip 0.02 g/kg fat-free mass) and following chronic 30-day oral administration of ascorbic acid (500 mg/day). Plasma ascorbic acid concentration was not different between young and older adults and was increased similarly, independent of age [change (Delta) acute = 1,055 +/- 117%; Delta chronic = 62 +/- 19%]. Oxidized low-density lipoprotein concentration was greater (P < 0.001) in older (57 +/- 5 U/l) compared with young (34 +/- 3 U/l) adults and was reduced in both groups (P < 0.02) following acute (Delta = -6 +/- 2%) but not chronic (P = 0.18) ascorbic acid administration. Control (baseline) Vo(2max) and Q(max) were positively related (r = 0.76, P < 0.001) and were lower (P < 0.05) in older (34 +/- 2 ml.kg(-1).min(-1); 16.1 +/- 1.1 l/min) compared with young (43 +/- 3 ml.kg(-1).min(-1); 20.2 +/- 0.9 l/min) adults. Following ascorbic acid administration, neither Vo(2max) (young acute = 41 +/- 2; young chronic = 42 +/- 2; older acute = 34 +/- 2; older chronic = 34 +/- 2 ml.kg(-1).min(-1)) nor Q(max) (young acute = 20.1 +/- 0.9; young chronic = 19.1 +/- 0.8; older acute = 16.2 +/- 1.1; older chronic = 16.6 +/- 1.4 l/min) was changed. These data suggest that ascorbic acid administration does not affect the age-associated reduction in Q(max) and Vo(2max).

Adaptation, Physiological↗

Interaction between hydroquinone and ascorbic acid derivatives: quenching effect of organic solvents.

The interaction between hydroquinone (HQ) and ascorbic acid analogs was investigated. Semiquinone radicals (SQ.) generated by HQ were comparably scavenged by ascorbic acid, sodium ascorbate and ascorbate 6-palmitate, but much less efficiently by ascorbate 2,6-dipalmitate. Organic solvents, such as dimethysulfoxide (DMSO) or ethanol, which are utilized for solubilization of water-insoluble analogs, ascorbate 6-palmitate and ascorbate 2,6-dipalmitate, also scavenged SQ.. DMSO scavenged the SQ. more efficiently than ethanol. This suggests the importance of considering such a quenching effect of organic solvent in the study of the interaction between HQ and antioxidants. The involvement of the ascorbate radical for cytotoxicity induction is discussed.

Ascorbic Acid↗

Rapid spectrophotometric determination of ascorbic acid in citrus fruits.

A new spectrophotometric method has been developed for determining ascorbic acid in citrus fruits. The method is based on interaction between dimethoxydiquinone and ascorbic acid, followed by extraction with chloroform. The resulting chloroform solution gives a maximum absorption at 530 nm, a determination limit of 22.0 microng/ml, and a linear range from 22.0 to 97.5 microng/ml. The molar absorptivity of the chloroform solution was 1.62 x 10(3). The reaction was quantitative over the pH range from 3.0 to 7.0. Ascorbic acid in citrus fruits was successfully determined by this method. Comparison of results with those obtained by using the AOAC method showed excellent agreement; the average recovery for the analysis of orange, grapefruit, and lemon juices was 100 +/- 0.3%.

Ascorbic Acid↗

Determination of L-ascorbic acid in tomato by isotachoelectrophoresis. Application of computer simulation system for setting of determination conditions to avoid the mixed-zone problem.

When the isotachoelectrophoretical method is used with HCl-beta-alanine as the leading electrolyte solution (pH 3.6), ascorbic acid forms a mixed zone with glutamic acid, and it is difficult to separate the two. Therefore, the application of a computer simulation system to separate the two acids was investigated. This system can be used with compounds for which the absolute electrophoretical mobility and dissociation constant have already been determined. Values for glutamic acid alone were entered in the data bank "SIPS-1", and then those for ascorbic acid were estimated from the values of similar compounds. Values for aspartic acid were used, and the electrophoretical behavior of ascorbic and glutamic acids was simulated at pH range from 3 to 9.9. Based on this simulation, separation appeared possible at pH 9.0 to 10.0, and indeed, experimental determination of ascorbic acid was successfully performed with a leading electrolyte solution composed of HCl-ethanolamine (pH 9.4) without any glutamic acid interference. Even though ascorbic acid is highly susceptible to oxidation in an alkaline medium, because the ascorbic acid solution is injected at the interface of the leading and terminal electrolyte solutions in the electrophoretical procedure, it does not come in contact with air during electrophoresis. This explains why ascorbic acid can be determined in an alkaline medium.

Ascorbic Acid↗

Effects of ascorbic acid deficiency and of erythorbic acid on blood components in the Cynomolgus monkey.

Eight male Cynomolgus monkeys were fed an ascorbic acid-free total liquid diet until plasma levels decreased from a mean of 1.1 mg/dl to 0.04 mg/dl at 8 weeks. They showed no visible signs of scurvy. The animals were then given a daily oral dose of 10 mg ascorbic acid/kg body weight for 4 weeks, when the experiment was ended. Four of the animals were given, in addition, 200 mg erythorbic acid/kg body weight orally each day. In all animals repletion was accomplished in two to three weeks using return to initial plasma ascorbic acid levels as the criterion. During deficiency, blood cellular elements were found to be more resistant to depletion than plasma. For erythrocytes, this may be explained at least partially by the observation that in vitro uptake of ascorbic acid tended to be related inversely to blood ascorbic acid levels. However, no such relationship was seen in leucocytes or platelets. Other measurements made on blood did not vary in response to changing ascorbic acid levels. These include serum cholesterol; erythrocyte, leucocyte, or platelet counts; leucocyte differential; hemoglobin concentration; and hematocrit. Urinary hydroxyproline/creatinine ratios were also unchanged. Erythorbic acid, a stereoisomer of ascorbic acid and a common food additive, has been cited as a possible interferent in the determination of whole blood or plasma ascorbic acid, since in the guinea pig it is absorbed from the gut and no commonly used ascorbic acid analysis can distinguish between the isomers. Under conditions of the present experiment, however, no elevation of apparent whole blood or plasma ascorbic acid was produced by inclusion of high levels of erythorbic acid in the diet. Animals given erythorbic acid in addition to ascorbic acid during repletion did not differ from those given ascorbic acid alone in any aspect mentioned above.

Administration, Oral↗

Spectrophotometric determination of ascorbic acid in pharmaceutical preparations and fruit juices.

Conditions were established for the determination of ascorbic acid using phsophovanadotungstic acid as reagent. The method was applied to the determination of ascorbic acid in pure form, pharmaceutical preparations and fruit juices. The method is sensitive (2-24 micrograms ml-1 of ascorbic acid) and rapid and tolerates the presence of common ingredients usually found in fruit juices. The results obtained with the proposed method showed good agreement with those given by the standard method.

Ascorbic Acid↗

The effect of catalase on the inactivation of tyrosinase by ascorbic acid and by cysteine or glutathione.

When tyrosine was incubated with tyrosinase in the presence of ascorbic acid, dopa and 5-hydroxydopa were formed and the enzyme was inactivated. In the presence of catalase, more dopa and 5-hydroxydopa were formed because enzyme inactivation was prevented. Incubation of dopa and cysteine with small amounts of mushroom tyrosinase led to rapid inactivation of the enzyme. This inactivation was accelerated in the presence of catalase. New systems developed have been useful in demonstrating the role of hydrogen peroxide in tyrosinase inactivation by several compounds of importance in melanin biochemistry. Cysteine and glutathione inactivated tyrosinase. Addition of catalase increased the inactivation at high thiol concentrations, but decreased the inactivation at low concentrations. Ascorbic acid and 5-hydroxydopamine also inactivated tyrosinase, but with these compounds inactivation was completely prevented by addition of catalase. The inactivation by dopamine was negligible under the experimental conditions. Inactivation of tyrosinase by ascorbic acid and by 5-OH-dopamine was found dependent on oxygen, whereas inactivation by cysteine and glutathione was independent of oxygen. Large amounts of serum albumin protected tyrosinase from inactivation by ascorbic acid and 5-OH-dopamine, but did not prevent inactivation by cysteine and glutathione. The presence of substrate had a protective effect on the inactivation of tyrosinase by cysteine.

Ascorbic Acid↗

[Ascorbic acid level and the indicators of cellular immunity in patients with hepatitis A during pathogenetic therapy].

Ascorbic acid content was assayed in plasma and neutrophils of peripheral blood in 260 patients with virus hepatitis A during acute period of the disease. The data obtained have evidenced C-hypovitaminosis in these patients, that was more pronounced in the winter-spring period, according to the disease severity 300 mg of ascorbic acid for 1.5 g of galascorbin/day have proved to be the most optimal dose for vitamin C deficiency elimination. A significant decrease in T-lymphocyte level and an increase in 0-cell content were recorded in the acute period of virus hepatitis A. Ascorbic acid drugs promoted more rapid recovery of T-lymphocyte content in the peripheral blood that has confirmed the necessity of vitamin C administration in combined pathogenetic therapy of patients with virus hepatitis A.

Ascorbic Acid↗