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The possible value of ascorbic acid as a prophylactic agent for urinary tract infection.

The effect of ascorbic acid on urine pH was studied in spinal cord injury patients. Their urine was not colonized by urease positive microorganisms. The study was designed to compare the baseline urine pH value and the urine pH value after the administration of placebo or ascorbic acid 500 mg/6 h. The diet and medical treatment were not controlled. A significant decrease in urine pH value was not obtained. There was no clinical benefit from the use of ascorbic acid.

Adolescent↗

Effect of sorbinil and ascorbic acid on myo-inositol transport in cultured rat Schwann cells exposed to elevated extracellular glucose.

The effect of long-term (2 weeks) exposure to 0-50 mM glucose and 0-1 mM sorbitol on myo-inositol metabolism was studied in cultured rat Schwann cells. Experiments were carried out to determine the effect of sorbinil and ascorbic acid on myo-inositol uptake in rat Schwann cells cultured in the presence of increased extracellular glucose or sorbitol. myo-Inositol uptake and its incorporation into phospholipids decreased significantly when cells were grown in > or = 30 mM glucose for a period of 2 weeks. This inhibitory effect was partly blocked by sorbinil, an aldose reductase inhibitor, in a dose-dependent fashion. Significant prevention was achieved with 0.5 and 1 mM sorbinil. Ascorbic acid also prevented the reduction in myo-inositol uptake due to excess extracellular glucose, at 3 and 30 microM concentrations, but not at 300 microM. Neither sorbinil nor ascorbic acid could prevent the alterations in myo-inositol transport in cells exposed to high sorbitol levels for the same period of time. These data suggest that glucose-induced alteration of myo-inositol transport in Schwann cells is mediated, at least in part, via sorbitol accumulation. This myo-inositol transport impairment is prevented by sorbinil and also by ascorbic acid. Ascorbic acid may hold a fresh promise for the treatment/prevention of diabetic neuropathy/complications, at least as an adjunct therapy along with known aldose reductase inhibitors.

Aldehyde Reductase↗

In vivo assessment of iron and ascorbic acid in psoriatic dermis.

Reactive oxygen species play an important role in inflammatory skin diseases such as psoriasis. Reactive oxygen species synthesis is catalysed by iron and some species are scavenged by ascorbic acid. The aim of this work was to assess iron and ascorbic acid in uninvolved and involved psoriatic dermis and to compare the corresponding concentrations in the dermis of healthy subjects. Microdialysis associated with atomic absorption spectrometry and gas chromatography-mass spectrometry was used to assess iron and ascorbic acid, respectively. Seven psoriatic patients and five healthy volunteers were studied. Iron concentrations in the involved (57.1 +/- 19.3 microg/l) and uninvolved (49.7 +/- 27.1 microgl/l) psoriatic dermis were higher than the corresponding value determined in the dermis of healthy subjects (21.8 +/- 2.4 microg/l) (p<0.05). Ascorbic acid in involved (47.3 +/- 8.2 microg/ml) and uninvolved (42.0 +/- 14.0 microg/ml) psoriatic dermis was statistically lower than that found in healthy dermis (176.8 +/- 29.0 microg/ml) (p<0.05). These results demonstrate that psoriatic patients exhibit high iron and low ascorbic acid concentrations in the dermis, but there were no significant differences between involved and uninvolved skin.

Adult↗

Levels of total ascorbic acid and histamine in the blood of women during the 3rd trimester of normal pregnancy.

Levels of total ascorbic acid and histamine in the peripheral venous blood of women during the third trimester of normal pregnancy have been estimated. The results suggest that ascorbic acid acts as a modulator to control the synthesis and/or release of histamine in the body. Low levels of ascorbic acid may be essential to stimulate the synthesis and/or release of histamine while in high concentrations it may function to inhibit the release and/or to enhance the breakdown of excessive quantities of histamine in the body. Substantial evidence is now available that histamine, perhaps its nascent variety, is essential for growth and repair processes in the body. It is possible that ascorbic acid in low concentrations acts to stimulate this variety of histamine while its high concentrations act to control the levels of histamine released from storage sites which contain preformed histamine.

Adolescent↗

Histamine and ascorbic acid: a survey of women in labor at term and significantly before term.

In ascorbic acid-requiring species (human, guinea pig), elevations of circulating histamine occur as the result of marginal ascorbic acid status. Marginal ascorbic acid status during pregnancy is associated with preeclampsia, abruption, and prematurity. Furthermore, circulating histamine is known to be elevated in these complications perhaps as a result of placental dysfunction which diminishes normal placental histaminase. We hypothesized that women with preeclampsia and premature labor would have elevated histamine and the lowest concentrations of ascorbic acid. Plasma total whole blood histamine and ascorbic acid were surveyed in women in term (T) and preterm (PT) labor. Blood histamine was elevated in PT compared to T labor but so was plasma ascorbate, indicating that marginal ascorbate status does not cause the elevated circulating histamine observed in PT. However, marginal ascorbate status concomitant with reduced placental histaminase may contribute to further increases in circulating histamine and to any pathology which might result from elevated histamine. Regression analysis of histamine on ascorbate for T and PT labor revealed a significant inverse relationship between ascorbate and histamine only in PT labor (p less than 0.027). An unexpected finding was that a history of maternal cigarette smoking, to a degree which resulted in marginal ascorbic acid status, confounded the relationship between ascorbate and circulating histamine in T labor.

Adult↗

[DNA-breaking action of ascorbic acid in the presence of Cu(II)/demethylcantharic acid complex].

Effects of various factors on the DNA-breaking action of ascorbic acid in the presence of Cu(II)/demethylcantharic acid complex were studied in phosphate buffer (pH 7.40), at 37.0 +/- 0.1 degrees C. It was shown that .OH produced from Fenton reaction of H2O2 which can be formed from the oxidation of ascorbic acid was responsible for the DNA-breaking action of ascorbic acid and the simple Fenton reaction cannot explain all the results.

Ascorbic Acid↗

Metabolic fate of an oral dose of 15N-labeled nitrate in humans: effect of diet supplementation with ascorbic acid.

The metabolic fate of a p.o. dose of 3.5 mmol 15N-labeled nitrate has been investigated in 12 healthy young adults. Samples of urine, saliva, plasma, and feces were collected over a period of 48 hr following administration of the dose. Subjects received either 60 mg of ascorbic acid, 2 g of ascorbic acid, or 2 g of sodium ascorbate per day. An average of 60% of the 15NO3- dose appeared in the urine as nitrate within 48 hr. Less than 0.1% appeared in the feces. The 15N label of nitrate was also found in the urine (3%) and feces (0.2%) in the form of ammonia or urea. The fate of the remaining 35% of the 15NO3- dose administered is unknown. No effect of ascorbic acid or sodium ascorbate on the nitrate and nitrite levels of plasma, saliva, urine, or feces was observed. A one-compartment pharmacokinetic model was used to describe the relationships between intake, plasma concentration, and urinary excretion of nitrate. The half-life of nitrate in the body was found to be approximately 5 hr, and its volume of distribution was about 30% of body weight. Daily endogenous biosynthesis of nitrate was estimated to be about 1 mmol/day.

Administration, Oral↗

Effects of L-ascorbic acid on ethanol-induced central nervous system depression in mice.

Male Swiss-Webster mice were administered ethanol immediately before a motor coordination test. Controls and animals treated with 1, 2 or 3 g/kg, IP, of ethanol remained on a suspended meter stick for 240 +/- 0, 232 +/- 8, 93 +/- 2 and 75 +/- 5 sec, respectively. Blood ethanol levels at the end of the test period (4 min) or when the animal fell from the meter stick were 1.02 +/- 0.03, 2.13 +/- 0.09 and 2.24 +/- 0.07 mg/ml for the 1, 2 and 3 g/kg dose of ethanol, respectively. Thirty min prior to ethanol (2 g/kg, IP) animals received L-ascorbic acid in doses of 500 or 1000 mg/kg, IP. Both doses of L-ascorbic acid significantly enhanced the duration of time that the animals spent on the meter stick. When animals were given 1 g/kg, IP, of ethanol their rate of walking (cm/min) on the meter stick was significantly increased over controls. Administration of L-ascorbic acid (1000 mg/kg, IP) 30 min prior to ethanol (1 g/kg) did not change the rate of locomotion. In experiments on ethanol-induced hypnosis (sleep-time), animals received L-ascorbic acid (250, 500, 1000 or 1500 mg/kg, IP) or saline 30 min prior to ethanol (4 g/kg, IP). L-ascorbic acid increased the time of onset of hypnosis significantly at doses of 1000 and 1500 mg/kg. With these doses of L-ascorbic acid sleep duration and blood ethanol content were not altered. L-ascorbic acid, however, increased ethanol-induced hypnosis at a dose of 500 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interaction of glutathione and ascorbic acid in guinea pig lungs exposed to nitrogen dioxide.

The interaction of two important water-soluble antioxidants, glutathione and ascorbic acid, was studied. The perfused guinea pig lung was found to contain about twice as much reduced glutathione as ascorbic acid. Nitrogen dioxide exposure decreased the levels of the two antioxidants both in vitro and in vivo. Ascorbic acid concentration was lowered to a greater extent than glutathione. The pulmonary ascorbic acid level was identical in both control and glutathione-deficient guinea pigs exposed to nitrogen dioxide, suggesting that there was little interaction between the two antioxidants in the lungs during oxidant stress.

Animals↗

Antioxidant activity of L-ascorbic acid in wild-type and superoxide dismutase deficient strains of Saccharomyces cerevisiae.

Much has been published on the non-enzymatic antioxidant L-ascorbic acid (vitamin C), but even so its interaction with endogenous cellular defense systems has not yet been fully elucidated. Our study investigated the antioxidant activity of L-ascorbic acid in wild-type strain EG103 (SOD) Saccharomyces cerevisiae and isogenic mutant strains deficient in cytosolic superoxide dismutase (sod1delta), mitochondrial superoxide dismutase (sod2delta) or both (sod1delta sod2delta), metabolizing aerobically or anaerobically with and without the stressing agent paraquat. The results show that during both aerobic and anaerobic metabolism there was a significant increase in the survival of both wild-type S. cerevisiae cells and the mutant cells (sod1delta, sod2delta and sod1delta sod2delta) when pretreated with L-ascorbic acid before exposure to paraquat. Exposure to paraquat resulted in higher catalase activity but this significantly decreased when the cells were pre-treated with L-ascorbic acid. These results demonstrate that due to the damage caused by paraquat, the antioxidant protection of L-ascorbic acid seems to be mediated by catalase levels in yeast cells.

Aerobiosis↗

Ascorbic acid and tyrosine metabolism in preterm and small-for-dates infants.

Ascorbic acid levels in plasma and leucocytes and urinary excretion of tyrosyl derivatives (TD) were determined in 11 normal, 18 preterm, and 4 small-for-dates infants. Concentrations of ascorbic acid in both plasma and leucocytes were found to be similar in the 3 groups. There was no difference in the basal levels of TD between normal and small-for-dates infants, but preterms showed higher basal excretion of TD than the other two groups. After protein load the excretion of TD was higher than the basal level in preterms. It was concluded that the altered metabolism of tyrosine observed in preterms is not the result of poor ascorbic acid status; and that tyrosine metabolism is influenced by the period of gestation rather than the body weight of the infant.

Ascorbic Acid↗

L-Ascorbic acid and lysosomal acid hydrolase activities of guinea pig liver and brain.

The effects of L-ascorbic acid deficiency on guinea pig hepatic and brain lysosomal hydrolases were examined. In general, hepatic beta-N-acetylhexosaminidase, beta-D-glucoronidase, alpha-D-galactosidase, alpha-D-mannosidase, and acid phosphatase were elevated in scorbutic animals. This appears to be independent of the starved state. Brain beta-D-glucoronidase and acid phosphatase followed a similar pattern to that observed with the liver enzymes, but brain beta-N-acetylhexosaminidase was not affected by L-ascorbic acid decreased the activity of hepatic beta-N-acetylhexosaminiadase was unaffected by dietary treatments although the activity of beta-N-acetylhexosaminidase A tended to increase in the scorbutic animals. Subcellular fractions were obtained from the three groups of animals and the recoveries of protein, beta-N-acetylhexosaminidase, and glucose-6-phosphatase estimated.

Acid Phosphatase↗

A rapid manual method for routine assay of ascorbic acid in serum and plasma.

A method is described for the assay of ascorbic acid in either serum or heparinized plasma. 1. The assay is based on the reduction of ferric chloride by ascorbic acid with the resulting ferrous ion quantitated by the addition of 2,4,6-tripyridyl-s-triazine to form a purple colour with a maximum absorbance at 595 nm. 2. Uric acid interference has been eliminated by the use of a high molarity acetate buffer and by optimising the amount of TPTZ and ferric chloride used. 3. Protein was found to cause rapid fading of the final colour; it was therefore necessary to remove the protein, by addition of 10% trichloroacetic acid, from the specimen prior to the final assay. This had the added advantage of assisting to stabilize the ascorbic acid prior to final assay. 4. All reagents used are easily obtained and no special equipment is required.

Ascorbic Acid↗

Transport of ascorbic acid and dehydroascorbic acid by pancreatic islet cells from neonatal rats.

Several amidated biologically active peptides such as pancreastatin, thyrotropin-releasing hormone, pancreatic polypeptide and amylin are produced in endocrine pancreatic tissue which contains the enzyme necessary for their final processing, i.e. peptidylglycine alpha-amidating mono-oxygenase (EC 1.14.17.3). The enzyme needs ascorbic acid for activity as well as copper and molecular oxygen. The present work shows that pancreatic islet cells prepared from overnight cultures of isolated islets from 5-7-day-old rats accumulate 14C-labelled ascorbic acid by a Na(+)-dependent active transport mechanism which involves a saturable process (estimated Km 17.6 microM). Transport was inhibited by ouabain, phloridzin, cytochalasin B, amiloride and probenecid. Glucose inhibited or stimulated uptake, depending on the length of incubation time of the cells. The uptake of dehydroascorbic acid was linearly dependent on concentration. Dehydroascorbic acid was converted to ascorbic acid by an unknown mechanism after uptake. The uptake of both ascorbic acid and dehydroascorbic acid was inhibited by tri-iodothyronine, and uptake of ascorbic acid, but not of dehydroascorbic acid, was inhibited by glucocorticoids. Isolated secretory granules contained a fairly low concentration of iron but a high concentration of copper.

Animals↗

Preventive effect of ascorbic acid against glucocorticoid-induced cataract formation of developing chick embryos.

Glucocorticoid administration to developing chick embryos is known to promote cataract formation with a decreasing level of glutathione in the lens. To gain further understanding of this process, the level of ascorbic acid, a biological antioxidant, in the lenses was measured during the course of glucocorticoid treatment. When 0.25 mumol of hydrocortisone hemisuccinate sodium (HC) were administered to 15-day-old chick embryos, the level of ascorbic acid in the lens began to decline after 30 hr and became around 40% of the control value at 48 hr after HC treatment. At this time about 90% of the lenses showed opacity in the nuclear region. However, the level of ascorbic acid in the cataractous lens recovered to the control level at 96 hr, a time when the lens has recovered from cataract formation. A triple application of ascorbic acid (20 mumol/egg) at 3, 10 and 20 hr after HC treatment significantly prevented lens opacification. The administration of ascorbic acid prevented the decline of ascorbic acid content and partially that of glutathione content in the lens caused by HC.

Animals↗

The protective effects of high-dose ascorbic acid on myocardium against reperfusion injury during and after cardiopulmonary bypass.

The protective effects of high-dose ascorbic acid (250 mg/kg) on the myocardium were observed in 85 patients undergoing Cardiopulmonary Bypass (CPB). The changes in serum Malonyldialdehyde (MDA). Creatine Phosphokinase (CPK), Creatine Phosphokinase isozyme (CPK-MB) and Lactic Dehydrogenase (LDH) in group B (n = 45, receiving ascorbic acid) were lower (p < 0.05) than in group A (n = 40, no ascorbic acid) during and after CPB. The MDA remained at a higher level two days postoperatively; CPK and CPK-MB, the sensitive and specific reflectors of myocardial injury, recovered very slowly in the control group (A) after the operation. The hearts in all the patients of group B resuscitated automatically intraoperatively while five cases (12.5%) needed defibrillation in group A. The cardiac index (CI) measured in ICU in group B was higher than in group A (p < 0.05). The patients needed shorter ICU and hospital stays in group B than in group A. The results indicate that ascorbic acid can act as a scavenger of free radicals to decrease the peroxidation of the lipids present in the cell membrane and remove the radicals to protect the myocardium from ischemia-reperfusion injury effectively during and after open-heart operation.

Ascorbic Acid↗

Assay of ascorbic acid in human crevicular fluid from clinically healthy gingival sites by high-performance liquid chromatography.

The volume of fluid on filter paper strips was measured with a Periotron, eluted, and the ascorbic acid measured by chromatography. In preliminary experiments, pre-impregnation of the strips with citric acid increased the recovery of standard ascorbic acid from 37 to 89% and significantly reduced loss of water from the strips over a 3 min period. Samples of crevicular fluid were then collected from clinically healthy gingival sites of 21 healthy volunteers using pre-impregnated strips and assayed for ascorbic acid concentration, together with samples of blood plasma. The mean ascorbic acid concentration in gingival crevicular fluid (207.3 mumol/l; SD: +/- 81.8) was significantly higher (p less than 0.001) than the corresponding plasma concentration (mean 72 mumol/l; SD: +/- 23.3).

Ascorbic Acid↗

The effect of ascorbic acid on arachidonic acid and prostaglandin E2 metabolism in B16 murine melanoma cells.

Ascorbic acid (Asc), arachidonic acid (AA) and prostaglandin E2 (PGE2) are reported to be important in maintaining the stability of the cell matrix. Asc has also been shown to influence fatty acid (FA) and PGE2 synthesis, with the result that effects of Asc on cell growth are suggested to be mediated through the metabolism of these two compounds. This study examined the effect of Asc, supplemented over the concentration range of 0-100 micrograms/ml, on the in vitro cell growth of non-malignant LLCMK (monkey kidney) cells and malignant B16 murine melanoma cells. The effects of Asc supplementation on AA and PGE2 levels in the cell stroma and membrane fractions of the two cell types was also determined. Asc had no significant inhibitory or stimulatory effect on the growth of either the B16 or LLCMK cells. The total percentage AA composition determined in the B16 control cells (combined stroma and membrane fractions), was similar to that determined in the LLCMK control cells. Asc supplementation of the B16 cells, resulted in an inverse relationship between B16 cell growth and total percentage AA composition. PGE2 concentration in the control B16 cells (combined stroma and membrane fractions) was significantly higher than that detected in the control LLCMK cells. No PGE2 was detected in the B16 stroma fraction, with all appearing to be located in the membrane fraction. However, upon the supplementation of the B16 cells with increasing Asc concentrations, PGE2 appeared to be mobilized from the membrane fraction, resulting in increasing PGE2 levels in the stroma fraction relative to the membrane fraction. This was accompanied by a significant decrease in PGE2 concentration, in the membrane fraction. B16 cell growth and total (stroma and membrane fractions) PGE2 concentration in these cells was inversely related, when cultures were supplemented with increasing levels of Asc. Asc supplementation of the LLCMK cells did not appear to have any significant effect on AA or PGE2 metabolism in these cells.

Animals↗