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PubMed2001

Topical L-ascorbic acid: percutaneous absorption studies.

BACKGROUND: Reactive oxygen species generated by ultraviolet light result in photocarcinogenic and photoaging changes in the skin. Antioxidants protect skin from these insults. OBJECTIVE: This study defines formulation characteristics for delivering L-ascorbic acid into the skin to supplement the skin's natural antioxidant reservoir. METHODS: L-ascorbic acid or its derivatives were applied to pig skin. Skin levels of L-ascorbic acid were measured to determine percutaneous delivery. RESULTS: L-ascorbic acid must be formulated at pH levels less than 3.5 to enter the skin. Maximal concentration for optimal percutaneous absorption was 20%. Tissue levels were saturated after three daily applications; the half-life of tissue disappearance was about 4 days. Derivatives of ascorbic acid including magnesium ascorbyl phosphate, ascorbyl-6-palmitate, and dehydroascorbic acid did not increase skin levels of L-ascorbic acid. CONCLUSIONS: Delivery of topical L-ascorbic acid into the skin is critically dependent on formulation characteristics.

Administration, Cutaneous↗
PubMed1979

Ineffectiveness of ascorbic acid therapy in nephropathic cystinosis.

Because high concentrations of ascorbic acid (0.57 mM) lower the free (nonprotein) cystine content of cultured cystinotic skin fibroblasts by over 50 per cent, we did a double-blind clinical trial to establish whether this drug would benefit cystinotic children. Sixty-four patients were randomized into the study; 32 received ascorbic acid (200 mg per kilogram of body weight per day), and 32 placebo. The study was terminated after approximately two years because there was no indication that vitamin C was beneficial and accumulating evidence that it might be harmful. Of 11 patients who left the study because of death or the requirement for dialysis or renal transplantation, eight were receiving ascorbic acid. The estimated relative risk (treatment vs. control) of an adverse event was R = 2.7, with a 90 per cent confidence interval of (0.8, 11.5). The serum creatinine concentration increased 0.53 mg per deciliter per year in patients receiving vitamin C and 0.24 mg per deciliter per year in patients receiving placebo (P = 0.08).

Ascorbic Acid↗
PubMed1997

Interaction of ethanol and ascorbic acid on lipid metabolism in guinea pigs.

Influence of excessive intake of ascorbic acid (AA) on alcohol induced hyperlipidemia was investigated. In the present study four groups of male guinea pigs were maintained for 30 days as follows: (1) Control group (1 mg AA/100 g body wt). (2) Ethanol group (I mg AA + 9 g ethanol/100 g body wt). (3) AA group (25 mg AA/100 g body wt). (4) AA + Ethanol group (25 mg AA/100 g body wt + 9 g ethanol 100 g body wt). It was shown that tissue ascorbic acid concentration increased with the intake of mega dose of AA. Alcohol administration depleted tissue ascorbic acid content. But coadministration of AA and alcohol enhanced AA levels in comparison with the ethanol group. Alcohol induced hyperlipidemia was reduced in almost all the tissues by the intake of ascorbic acid. This was observed to be due to increased hepatic catabolism of cholesterol to bile acids. However cholesterogenesis was enhanced as evidenced by the increased HMG CoA activity. Thus the results indicate that the mega dose of AA ingestion is beneficial in reducing alcohol induced hyperlipidemia and AA deficiency.

Animals↗
PubMed1999

Decalcification by ascorbic acid for immuno- and affinohistochemical techniques on the inner ear.

An ascorbic acid decalcifying solution was applied to immuno- and affinohistochemical studies on the inner ear. Rat inner ears fixed in 4% paraformaldehyde in PBS or in 2% acetic acid in ethanol solutions were adequately decalcified in an ascorbic acid solution, at a temperature of 4 degrees C. The decalcifying solution was prepared with 1% ascorbic acid and 0.84% sodium chloride in distilled water (pH 2.5-2.6). The decalcification time was in a direct relationship to the specimen calcification. In this study, two neuroactive substances (gamma-aminobutyric acid and calcitonin gene-related peptide), neurofilaments, and the galectine endogenous lectin were successfully detected immunohistochemically.

Animals↗
PubMed1993

Ascorbic acid inhibits protein tyrosine phosphatases in NIH 3T3 cells expressing human epidermal growth factor receptors.

1. Physiological concentrations of ascorbic acid inhibited PTPase activity in HER 14 cells. 2. Higher concentrations of ascorbic acid produced a weaker inhibitory effect on PTPase activity in HER 14 cells. 3. EGF prevented the inhibitory effect of ascorbic acid on PTPase activity in HER 14 cells. 4. The inhibitory effect of physiological concentrations of ascorbic acid on PTPase activity depends on density of the cell culture, with less dense populations exhibiting greater inhibition of PTPase activity. 5. These observations suggest that ascorbic acid might have a modulatory role in cellular phosphorylation-dephosphorylation events.

3T3 Cells↗
PubMed1976

Ascorbic acid prevents corneal ulceration and perforation following experimental alkali burns.

Depressed aqueous humor glucose and ascorbic acid levels returned to control values within 14 days following a 20 sec, 6 mm. diameter, 1N sodium hydroxide burn of the rabbit cornea. These corneas did not ulcerate or perforate. After a 20 sec., 12 mm. diameter, 1N sodium hydroxide burn, aqueous humor glucose levels returned to normal values, but ascorbic acid levels remained significantly depressed for up to 30 days. These corneas became markedly ulcerated in about 60 per cent of animals and frequently perforated. Following 12 mm. alkali burns, rabbits treated daily with 1.5 Gm. of subcutaneous ascorbic acid rarely developed corneal ulcerations and the corneas did not perforate. It is suggested that exogenous maintenance of adequate aqueous humor levels of ascorbic acid overcomes the relatively scorbutic state of the anterior segment induced by a 12 mm. alkali burn, thereby impairing the development of corneal ulceration and perforation. Elevated aqueous humor levels of ascorbic acid had no influence on corneal epithelial cell migration patterns following alkali burns.

Alkalies↗
PubMed1984

Effect of ascorbic acid and some reducing agents on N-nitrosopiperidine metabolism by liver microsomes.

The effect of ascorbic acid on the oxidation of N-nitrosopiperidine by a microsomal preparation obtained from guinea-pig liver has been examined. The metabolites from the oxidation of N-nitrosopiperidine were found to be 5-hydroxypentanal (about 1.93%), N-nitroso-3-hydroxypiperidine (about 0.02%), and N-nitroso-4-hydroxypiperidine (about 0.15%). With microsomes separated from the liver of guinea-pigs pretreated with phenobarbital and 3-methylcholranthrene, the yields of N-nitroso-3-hydroxypiperidine and N-nitroso-4-hydroxypiperidine were found to decrease upon increasing the concentration of ascorbic acid in the reaction mixture. In the presence of small amounts of ascorbic acid, the yields of these compounds with untreated liver microsomes apparently increased, while the presence of larger amounts of ascorbic acid caused a decrease in the yields of these metabolites. In contrast with the yields of N-nitroso-3-hydroxypiperidine and N-nitroso-4-hydroxypiperidine, that of 5-hydroxypentanal decreased with increasing amounts of ascorbic acid.

Aldehydes↗
PubMedDate not supplied

Assessment of ascorbic acid stability in different multilayered parenteral nutrition bags: critical influence of the bag wall material.

BACKGROUND: The recent development of multilayered bags has minimized ascorbic acid oxidation in parenteral nutrition (PN) admixtures. However, the gas-barrier property of multilayered bags depends on their plastic material. This study compared ascorbic acid stability in different multilayered bags under experimental conditions. METHODS: Oxygen permeability of a newly developed 6-layered bag (6-L) was compared with a highly mechanical-resistant 3-layered bag (3-L(R)) and a highly flexible 3-layered bag (3-L(F)) using gas chromatography. Ascorbic acid stability was assessed by iodine titration in bags filled with 2.5 L H(2)O and 40 g carbohydrates after setting residual O(2) content at < or =1 or > or =5 ppm. The effect of storage at 4 degrees C, 21 degrees C, and 40 degrees C on ascorbic acid stability was assessed over 48 hours in a complete PN admixture (ie, 330 g carbohydrates, 100 g lipids, 96 g amino acids and trace elements) using high-pressure liquid chromatography. RESULTS: Oxygen permeability was markedly reduced in 6-L bags (0.5 mL O(2) /m(2)/d) compared with 3-L(R) (150 mL O(2) /m(2)/d) and 3-L(R) (1500 mL O(2)/m(2)/d). Accordingly, ascorbic acid was more stable in 6-L bags (half-life [T(1/2)] = 16 days up to 40 degrees C) than in 3-L(R) (T(1/2) = 9 days at 4 degrees C, 47 hours at 21 degrees C and 29 hours at 40 degrees C) and 3-L(F) (T(1/2) = 15 hours at 4 degrees C, 10 hours at 21 degrees C, and 6 hours at 40 degrees C). During the first 6 hours after PN admixture compounding, an additive ascorbic acid loss of 4.6 +/- 0.5 mg/L/ppm O(2) occurred because of residual O(2) in the bag. CONCLUSIONS: The new combination of plastic layers and careful O(2) monitoring during the filling process allowed near to complete prevention of ascorbic acid degradation in multilayered PN bags during 48 hours, regardless of the storage temperature.

Ascorbic Acid↗
PubMed1989

Behavior of 3,4-endiol form of 2,3-diketo-gulono-delta-lactone formed from dehydro-L-ascorbic acid in deoxygenated and neutral solution.

The formation of L-ascorbic acid (AsA) was observed when dehydro-L-ascorbic acid (DHA) was dissolved in neutral buffer solutions under N2 bubbling at room temperature. The reduction of DHA was done with the lactonized compound of 2,3-diketo-L-gulonic acid (DKG), that is, the 3,4-endiol form of 2,3-diketo-gulono-delta-lactone (3,4-End DKGL). 3,4-End DKGL was formed from DHA or DKG (yield about 10%) under N2 bubbling in neutral buffer solution (pH 7.2). This material was not stable in neutral or alkaline solutions. 3,4-End DKGL suppressed more strongly the linoleic acid (LA) peroxidation in the medium containing 20% EtOH and 10 mM LA than did AsA. This may suggest the possibility that 3,4-End DKGL reproduces AsA from DHA in physiological status.

2,3-Diketogulonic Acid↗
PubMed1981

The antiscorbutic action of L-ascorbic acid and D-isoascorbic acid (erythorbic acid) in the guinea pig.

Female guinea pigs were fed a scorbutigenic diet supplemented with either L-ascorbic acid or D-isoascorbic acid or combinations of these. Their responses were judged by changes in body weight, serum alkaline phosphatase levels, wound healing, and tooth structure. Large additions (100 mg daily) of D-isoascorbic acid to the scorbutigenic diet resulted in normal growth over a 7-wk period and normal serum alkaline phosphatase levels, tooth structure development, and collagen formation after wounding. The addition of 0.5 or 5.0 mg of L-ascorbic acid to this high D-isoascorbic diet improved neither growth rate nor collagen deposition during wound healing. On the basis of changes in tooth structure, D-isoascorbic acid has 1/20 the potency of L-ascorbic acid. Its effect is additive to subminimal maintenance levels of L-ascorbic acid implying that there is no competitive inhibition in the utilization of the two compounds. The relatively weak activity of D-isoascorbic acid is probably due to poor transport to the tissues and ineffective binding to functional sites. This explains why the onset of scurvy is much more rapid after withdrawal of D-isoascorbic acid from the diet when it had been the sole antiscorbutic dietary constituent. It is concluded that D-isoascorbic acid is a "weakly" antiscorbutic agent on the basis that it is both poorly absorbed and retained by the tissue; that in fact it may, to the degree that it is taken up by the tissues and retained, be equal in antiscorbutic potency to L-ascorbic acid.

Alkaline Phosphatase↗
PubMed1987

Effects of ascorbic acid supplementation on liver, lung and kidney microsomal drug metabolizing enzymes of the guinea-pig.

1. Male guinea-pigs were administered 8, 180 and 360 mg ascorbic acid/day via drinking water for 1 and 2 months. The two high levels of ascorbic acid were not able to produce saturation in either blood or any of the three tissues (liver, lung and kidney) while the lowest ascorbic acid level was sufficient to prevent scurvy. 2. There was no significant differences among the groups receiving three distinct ascorbic acid levels in body weights, tissue weights or protein contents. 3. No significant alterations were observed in microsomal ethylmorphine N-demethylase activity of any of the three tissues among the groups after experimental periods. 4. The two high ascorbic acid levels produced significant increases in liver microsomal aniline 4-hydroxylase activity as compared to the lowest supplementation of ascorbic acid after 2 months. However, no significant enzyme activity changes were found among the groups after 1 month. 5. In lung, after 1 month significant increase was observed in microsomal aniline 4-hydroxylase activity with the two high ascorbic acid levels as compared to the lowest supplementation of ascorbic acid whereas after 2 months no significant changes were observed. 6. Kidney microsomal aniline 4-hydroxylase activity was unaffected by changes in ascorbate status.

Aniline Hydroxylase↗
PubMed1986

Effects of ascorbic acid on alkaline phosphatase activity and hormone responsiveness in the osteoblastic osteosarcoma cell line UMR-106.

L-ascorbic acid at physiological concentrations (10 micrograms/ml) increased alkaline phosphatase activity in the osteoblastlike rat osteosarcoma cell line, UMR-106. The increase was dose-dependent and detectable at 6 hours after the addition of 100 micrograms/ml ascorbic acid to the medium. Treatment of the cells with 100 micrograms/ml ascorbic acid potentiated the response of cAMP to both PTH and PGE1, while cell growth was inhibited. Furthermore, the number of colonies formed by the cells grown in the soft agar was significantly reduced by increasing concentrations of ascorbic acid. These results indicate that ascorbic acid might play some role in the differentiation of osteoblasts.

Alkaline Phosphatase↗
PubMed1995

The effect of four levels of ascorbic acid and two levels of calcium on eggshell quality of forced-molted White Leghorn hens.

The present experiment evaluated the effect of four levels of ascorbic acid (0, 100, 250, and 500 ppm) and two levels of calcium (3.0 and 3.5%) on the productivity and eggshell quality of molted Single Comb White Leghorn hens, housed four per 30.5 cm wide x 45.7 cm deep cage. The 4 x 2 factorial treatment combinations were randomly assigned to eight blocks of cages. Egg production increased (P < .06) an average of 5% for the levels of 250 and 500 ppm ascorbic acid. No differences were observed for feed consumption, egg weight, and shell thickness for the different levels of ascorbic acid or calcium in the diet. An increase (P < .01) was observed for specific gravity, as the levels of ascorbic acid increased. Increasing the level of calcium from 3.0 to 3.5% increased (P < .01) specific gravity from 1.073 to 1.075. Shell weight increased (P < .01) with the higher levels of ascorbic acid (250 and 500 ppm). No interactions were observed between the levels of ascorbic acid and calcium. Results suggest that supplementing ascorbic acid to molted laying hens can be beneficial to egg production and eggshell quality.

Animal Feed↗
PubMed1986

Necessity of ascorbic acid in the radioligand binding assay for [3H]5-hydroxytryptamine.

Evidence is presented to suggest that ascorbic acid is required in the radioligand binding assay for [3H]5-hydroxytryptamine ([3H]5-HT, [3H]serotonin). In the absence of ascorbic acid, oxidation of [3H]5-HT occurred if the radioligand solution was left on ice for 1 or 3 hr. The oxidative products were detectable by thin-layer chromatography. They increased the binding significantly, although there was only slight oxidation (less than 1%) of the [3H]5-HT. When ascorbic acid was not used in the radioligand binding assay for [3H]5-HT, even though [3H]5-HT was prepared immediately before incubating with the membranes from the cortex of the rat, the binding also increased. The increased binding of [3H]5-HT had a low affinity (Kd = 14 nM) and high B max (1180 fmol/mg protein), compared to that in the presence of ascorbic acid (Kd = 5 nM; B max = 210 fmol/mg protein). However, the increased binding was not receptor-related because the additional radioactivity was not displaceable by excess of unlabelled 5-HT (10 microM) or d-LSD (d-lysergic acid iethylamide) and anomalous "specific binding" occurred in boiled membranes from cortex, in which the binding sites for 5-HT were destroyed. These results suggest that oxidation of [3H]5-HT may occur during the incubation with membranes and that ascorbic acid is therefore required as an antioxidant.

Animals↗
PubMed1992

The stability of ascorbic acid in TPN mixtures stored in a multilayered bag.

Because of the susceptibility of some vitamins to oxidation, they are not normally added to TPN mixtures until shortly before addministration. Vitamin C (ascorbic acid) is oxidised rapidly, especially in the presence of trace elements. The aim of this study was to investigate the stability of ascorbic acid in complete TPN mixtures in Ultrastab multilayer bags, which are designed to reduce oxygen transmission and thus oxidation, in comparison with standard EVA bags. Ascorbic acid content was determined in two typical TPN mixtures providing 16 g nitrogen, 2000 kilocalories, electrolytes, trace elements and multivitamins, with and without fat emulsion, during storage at 5 degrees C for up to 3 months. In EVA bags ascorbic acid degraded by more than 75% during 24 h and was undetectable in 2-3 days. In contrast, there was a comparatively small initial loss of 15-30% ascorbic acid in mixtures stored in multilayer bags, with little further loss during 1-3 months. Bags containing fat emulsion retained higher concentrations of ascorbic acid after storage compared to those without fat emulsion, but all mixtures in multilayer bags maintained 60-80% ascorbic acid activity after 3 months. Since ascorbic acid is the most oxygen-sensitive vitamin, complete TPN mixtures with vitamins could be compounded in multilayer bags for an extended shelf life, rather than admixing just prior to administration.

Journal Article↗
PubMed1985

A double blind placebo controlled trial of ascorbic acid in obesity.

A double blind placebo controlled trial of ascorbic acid was carried out in 41 severely obese subjects. 38 patients completed the 6 week trial. 19 received 3g of ascorbic acid per day, 19 received placebo. The weight loss during the trial was small in both groups but was significantly greater in the ascorbic acid treated group.

Ascorbic Acid↗
PubMedDate not supplied

Topical activity of ascorbic acid: from in vitro optimization to in vivo efficacy.

We present here a new cosmetic formula system containing 3% ascorbic acid based on an optimized oil-in-water (O/W) emulsion. This formulation demonstrated a good long-term stability of the active ingredient and also of the emulsion itself. It could be deduced from in vitro release studies that this O/W emulsion enabled a better release of the hydrophilic active agent than an alternative W/O emulsion. By measuring the ultraweak photon emission, which is a well-established parameter for the oxidative stress in the skin, the high in vivo antioxidant capacity of 3% ascorbic acid was demonstrated after 1 week of product application. This placebo-controlled study also proved that ascorbic acid in an O/W cream reduced oxidative stress in human skin significantly better than the derivative sodium ascorbyl-2-phosphate, a more stable vitamin C replacement commonly used in cosmetic formulations. With increasing age, the number of papillae in the epidermal-dermal junction zone in human skin are reduced. This implies a possible consequence of reduced mechanical resistance of the skin and impaired supply of the epidermis with nutrients. In a 1-month placebo-controlled study on 25 human volunteers, a significant increase in the number of dermal papillae after application of the 3% ascorbic acid cream was demonstrated, using a confocal laser scanning microscope. Fine lines and wrinkles are a characteristic sign of aged and especially photo-aged skin. Application of 3% ascorbic acid in a 12-week placebo-controlled usage study indicated a significant reduction of facial wrinkles. Altogether, 3% ascorbic acid in a cosmetic O/W emulsion has been shown to be appropriately stable and to enable a good release of the active agent in vitro as a precondition for a high efficacy in vivo. Application in vivo resulted in a significant reduction of oxidative stress in the skin, an improvement of the epidermal-dermal microstructure and a reduction of fine lines and wrinkles in aged skin. These results were received within a relatively short period of time of product application.

Administration, Cutaneous↗