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In vitro studies of the interaction between ascorbic acid and rat tail tendon.

Ascorbic acid (in its normal and oxidised forms) enhances the mechanical and thermal stability of rat tail tendon. Its effectiveness increases with the concentration but levels off at a value approximately 5 times normal physiological concentration (1--2 mg/100 ml). An analogue, D-isoascorbic acid is also effective, but to a lesser extent. There is some evidence that it reduces reducible aldimine links, especially in young tissues. However, for the most part, its effects are reversible.

Aging↗

The role of ascorbic acid in the control of flowering time and the onset of senescence.

Ascorbic acid (AA) is not only an important antioxidant, it also appears to link flowering time, developmental senescence, programmed cell death, and responses to pathogens through a complex signal transduction network. The biological activity of AA is defined by its oxidation and subsequent regeneration into the reduced form. Some studies suggest that the total endogenous level of AA influences induction of flowering and senescence. Both processes require the co-ordinated regulation of gene expression, which is mediated by various phytohormones. For example, gibberellins and salicylic acid are known to promote flowering, but inhibit or retard senescence in Arabidopsis. Ethylene and abscisic acid accelerate senescence. Ascorbic acid serves as an important co-factor for the synthesis of some of these hormones. Therefore, it is assumed that AA affects phytohormone-mediated signalling processes during the transition from the vegetative to the reproductive phase and the final stage of development, senescence. This review summarizes recent reports that investigate the effect of AA on flowering time and the onset of senescence. An attempt was made to bring these findings in context with previously characterized flowering and senescence pathways and a model is proposed that may explain how AA influences flowering and senescence both under long- and short-day conditions in Arabidopsis.

Aging↗

The use of water-soluble bioflavonoid-ascorbic acid complex in the treatment of recurrent herpes labialis.

The efficacy of a water-soluble bioflavonoid-ascorbic acid complex was evaluated in the treatment of fifty episodes of recurrent herpes labialis. Twenty episodes were treated with a complex of 600 mg. of water-soluble bioflavonoids and 600 mg. of ascorbic acid, administered in equal increments three times daily. Twenty episodes were treated with a complex of 1,000 mg. of water-soluble bioflavonoids and 1,000 mg. of ascorbic acid, administered in equal increments five times daily. Ten episodes were treated with a lactose placebo. The therapeutic regimen was maintained for 3 days after the recognition of the initial symptoms associated with recurrent herpes labialis. The water-soluble bioflavonoid-ascorbic acid complex was observed to reduce vesiculation and to prevent the disruption of the vesicular membrane. The therapeutic measure was found to be most effective when initiated during the prodomal stage of the disease process. Optimum remission of symptoms was observed in 4.2 +/- 1.7 days with the 600 mg. dosage of the water-soluble bioflavonoid-ascorbic acid complex. No adverse reactions were reported by any of the patients who participated in this investigation.

Ascorbic Acid↗

Protective effect of flavonoids and tocopherol in high altitude hypoxia in the rat: comparison with ascorbic acid.

The mixture of flavonoids (silymarin) from Carduus Marianus (0.9 mg.g-1 body weight) and/or ascorbic acid (0.4 mg.g-1 body weight) were administered in the food to 21 day-old (b.w. 35-45 g) rats for one week. Then the animals were exposed, in a hypobaric chamber, to simulated altitude 8,000-12,000 m for one hour. Mean lethal altitude was calculated by the Behrens equation: it was 10,150 m in controls, 10,550 m in ascorbic acid treated, 10,500 m in silymarin and tocopherol treated and 10,450 m in animals, receiving both ascorbic acid and silymarin. Thus silymarin protected the animals against lethality of high-altitude hypoxia. The effect of ascorbic acid and silymarin were not additive.

Altitude Sickness↗

Growth and ascorbic acid metabolism in rats and guinea pigs fed cereal diets.

The nutritional values of the whole grain principal cereals, namely, wheat, rice, corn, and a millet bajra, were investigated by growth studies and studies on ascorbic acid metabolism in rats and guinea pigs. Growth was markedly retarded by feeding the rats unfortified whole grain cereals. Among the whole grain cereals, rice provided the lowest nutritional value, and the cooking of rice affected the nutritional value further. In weanling rats, ascorbic acid synthesis at the subcellular level was inhibited, and tissue storage of ascorbic acid was decreased in rats fed whole grain cereals. In guinea pigs fed whole grain cereals, the utilization of ascorbic acid was increased. Ascorbic acid supplementation at various levels indicated that the requirement for ascorbic acid increased five times in guinea pigs fed whole grain cereals. The increased intake of the vitamin was not needed when the whole grain cereals were enriched with 15% casein.

Animal Nutritional Physiological Phenomena↗

Changes in ascorbic acid metabolism of the offspring following high maternal intake of this vitamin in the pregnant guinea pig.

Guinea pigs were fed a control (0.05%) or a high (0.5%) ascorbic acid diet during the last half of pregnancy. When the pups were tested at 5 and 10 days of life the ones from the high-ascorbic-acid group demonstrated a marked increase in 14CO2 excretion, compared with the control pups, following an intraperitoneal injection of 14C-labeled ascorbic acid. When the animals were weaned to an ascorbic-acid-deficient diet signs of scurvy appeared earlier in the pups from the high vitamin C group and their survival was shorter. When excretion of labeled CO2 in both groups was correlated with the day of onset of scurvy signs, a linear correlation was found between these two parameters, suggesting that the earlier appearance of signs of scurvy in the experimental pups is secondary to an increased rate of ascorbic acid catabolism.

Animals↗

Cholecystokinin stimulates ascorbic acid secretion through its specific receptor in the perfused stomach of rats.

We have previously demonstrated that endogenous ascorbic acid is secreted into the gastric lumen by cholinergic stimulation in both conscious pylorus-ligated rats and the perfused stomach of unconscious rats, and that gastrin, a potent gastric stimulatory peptide hormone, has no effect. In the present study, the effects of some gastrointestinal peptide hormones on gastric ascorbic acid secretion were further examined in the perfused stomach of rats. An intravenous administration of cholecystokinin octapeptide (CCK-8) significantly increased gastric ascorbic acid secretion at a dose of 1.0 and 4.0 micrograms/kg, whereas the other three peptides examined, bombesin, neurotensin and substance P, showed no or little effect at the doses which were quite commonly employed for evaluation of various gastric functions. CCK-8-induced ascorbic acid secretion was reduced by pretreatment with proglumide, which is a CCK receptor antagonist, but not by pretreatment with atropine. These results indicate that gastric ascorbic acid secretion is physiologically regulated not only by muscarinic receptor-associated cholinergic stimulation but also by CCK receptor-associated humoral stimulation.

Animals↗

Ascorbic acid in fetal rat brain.

Ascorbic acid in fetal rat brain increases from 374 mg/g on the 15th day of gestation to 710 mg/g by the 20th day and remains at that level until birth. There is an 18% drop from this plateau after birth.

Age Factors↗

Stimulatory action of ascorbic acid on methyl mercury-induced lipid peroxidation in rabbit kidney cortex slices.

Effects of ascorbic acid on the methylmercuric chloride (MMC)-induced lipid peroxidation and the accumulation of MMC in rabbit kidney cortical slices were studied. Ascorbic acid had a powerful stimulatory effect on the MMC-induced lipid peroxidation, while it produced only a small increase in the MMC accumulation. This results suggests that ascorbic acid increases slightly the accumulation of MMC, but that the stimulatory action of ascorbic acid on the MMC-induced lipid peroxidation cannot be explained simply by the increase in the MMC accumulation.

Animals↗

Serum ascorbic acid and cardiovascular disease prevalence in U.S. adults: the Third National Health and Nutrition Examination Survey (NHANES III).

PURPOSE: To examine the relation between serum ascorbic acid concentration, which reflects dietary and supplement intake, and the prevalence of cardiovascular disease. METHODS: We analyzed data from 7658 men and women enrolled in the Third National Health and Nutrition Examination Survey (NHANES III). We calculated odds ratios and 95% confidence intervals (CI) to estimate the relative prevalence of cardiovascular disease, defined as self-reported angina, myocardial infarction, or stroke. Because we detected an interaction between serum ascorbic acid concentration and alcohol intake, we performed analyses stratified by drinking status. RESULTS: Among participants who reported no alcohol consumption, serum ascorbic acid concentrations were not independently associated with cardiovascular disease prevalence. Among participants who consumed alcohol, serum ascorbic acid concentrations consistent with tissue saturation (1.0-3.0 mg/dl) were associated with a decreased prevalence of angina (multivariate odds ratio (OR): 0.48; 95% CI: 0.23% to 1.03; p for trend = 0.06), but were not significantly associated with myocardial infarction or stroke prevalence. CONCLUSIONS: These results suggest the possibility of a biologic interaction between ascorbic acid and alcohol and that higher intakes of ascorbic acid may be associated with a decreased risk of angina among drinkers.

Adult↗

Effects of ascorbic acid and indomethacin on the airways of healthy male subjects with and without induced bronchoconstriction.

We have investigated the effects of ascorbic acid (1.0 gm orally) and indomethacin (50 mg orally) on airway tone in the basal state in six health nonsmoking male adults. Airway tone was assessed from measurements of specific airway conductance and flow rates interpolated from partial expiratory flow-volume curves by means of whole-body plethysmography and spirometry, respectively. Neither ascorbic acid nor indomethacin alone produced a significant change in basal tone. However, both the duration and intensity of the bronchoconstriction induced by methacholine aerosol (10 mg/ml for 30 sec) were significantly reduced by prior administration of ascorbic acid. This ameliorating action of ascorbic acid was blocked by ingestion of indomethacin. The results suggest that ascorbic acid exerts its effects by altering the production of a bronchodilator prostaglandin.

Airway Resistance↗

Intestinal absorption and metabolism of ascorbic acid in rainbow trout.

Transport and metabolism of the reduced and oxidized forms of vitamin C were evaluated in trout intestine in vitro. Transepithelial fluxes of [14C]ascorbic acid were determined with the substrate present at 10 microM. The mucosa-to-serosa flux was fourfold greater than the serosa-to-mucosa flux with ascorbic acid present in both bathing solutions. Cellular accumulation of the reduced molecule occurred with a final tissue-to-medium ratio of 1.64. Ascorbic acid influx across the brush-border membrane was determined under conditions that inhibit transport of other nutrients. Influx was not reduced because of the presence of the D- or L-stereoisomeric form of glucose but was highly dependent on the presence of Na in the bathing medium. Brush-border influx was saturable with a Km of 220 microM. Short-term (8 min) exposure of intestinal loops to the oxidized form of vitamin C, dehydro-L-ascorbic acid, was followed by high-performance liquid chromatography analysis of the 14C label present in the tissue. Total uptake of substrate was greater from the serosal solution than from the mucosal solution; in either situation most of the 14C label was found in the reduced state. It is concluded that transport and metabolic capabilities are present in the trout intestine to absorb oxidized and reduced forms of vitamin C and to help regulate the redox potential of circulating ascorbic acid by recycling dehydro-L-ascorbic acid.

Absorption↗

Accumulation of tropoelastin by a short-term ascorbic acid treatment in the culture medium of aortic smooth muscle cells in vitro.

Treatment of cultured smooth muscle cells with ascorbic acid resulted in an accumulation of tropoelastin in the culture medium in dose-dependent and exposure time-dependent manner under the condition in which collagen synthesis was stimulated 2-fold. The steady-state level of elastin mRNA was essentially unchanged, whereas collagen mRNA content increased 2-fold by ascorbic acid treatment. Newly synthesized tropoelastin was hydroxylated in the presence of ascorbic acid but was underhydroxylated in a scorbutic condition. Short pulse experiments showed that the secretion rate of tropoelastin was unaltered by ascorbic acid treatment. Pulse-chase experiment demonstrated that the level of fully hydroxylated tropoelastin in the medium of ascorbate-treated cells was greater than that of under-hydroxylated tropoelastin. These results indicate that accumulation of tropoelastin in the medium by ascorbic acid is related to an increased stability of hydroxylated tropoelastin and/or its impaired incorporation into insoluble elastin.

Actins↗

High-performance liquid chromatographic determination of ascorbic acid in serum using paired-ion chromatography and UV spectrophotometric detection.

A method is described for the determination of ascorbic acid in serum, using paired-ion high performance liquid chromatography with UV spectrophotometric determination. The advantages of the present procedure are its short analysis time, ease of performance and sufficient reliability. With this method it is possible to determine as little as 10 pmol (2 ng) serum ascorbic acid without any risk of oxidation. Correlation between the peak response and injected ascorbic acid concentration was found to be linear from 10 to 600 pmol (2 to 110 ng). An analytical recovery of 94.5 +/- 6.0 (mean +/- SD) was found by measuring a standard amount of ascorbic acid added to a serum pool on different days. Serum ascorbic acid concentrations were higher in adults (64 +/- 10 mumol/l) than in children (57 +/- 10 mumol/l).

Ascorbic Acid↗

Evolution and the biosynthesis of ascorbic acid.

The ability to synthesize ascorbic acid is absent in the insects, invertebrates, and fishes. The biosynthetic capacity started in the kidney of amphibians, resided in the kidney of reptiles, became transferred to the liver of mammals, and finally disappeared from the guinea pig, the flying mammals, monkey, and man. A similar transition in the biosynthetic ability was observed in the branched evolution of the birds.

Alcohol Oxidoreductases↗

Ascorbic acid supplement use and the prevalence of gallbladder disease. Heart & Estrogen-Progestin Replacement Study (HERS) Research Group.

To investigate the relation of ascorbic acid supplement use to gallbladder disease and cholecystectomy, we conducted a cross-sectional analysis of baseline from 2744 postmenopausal women, aged 44-79 years, enrolled in the Heart & Estrogen-progestin Replacement Study (HERS), a secondary coronary heart disease prevention trial. A total of 629 HERS participants (23%) reported a history of gallbladder disease. Of these, 508 (19%) also reported a history of cholecystectomy. In bivariate models, ascorbic acid supplement use was associated with a decreased prevalence of gallbladder disease [odds ratio (OR)=0.74; 95% confidence interval (CI), 0.57, 0.96] and a trend toward a decreased prevalence of cholecystectomy (OR=0.77; 95% CI, 0.58, 1.02). Because we detected significant interactions between ascorbic acid supplement use and alcohol consumption, multivariate analyses were performed stratified by drinking status. After adjustment for potential confounding variables, use of ascorbic acid supplements among drinkers was associated with a decreased prevalence of gallbladder disease (adjusted OR=0.50; 95% CI, 0.31, 0.81) and cholecystectomy (adjusted OR=0.38; 95% CI, 0.21, 0.67). Use of ascorbic acid supplements among non-drinkers was not significantly associated with either prevalence of gallbladder disease or cholecystectomy. Further study is necessary to confirm our findings and, specifically, to examine the combined effects of ascorbic acid and alcohol on cholesterol metabolism.

Adult↗