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PubMed1984

The effects of various levels of ascorbic acid intake upon growth and organ weights of guinea pigs.

The purpose of this study was to evaluate the systemic effects of varying levels of orally administered ascorbic acid during wound healing in guinea pig oral mucosa. Forty five Murphy/Hartley guinea pigs were randomly placed into four groups and fed an ascorbic acid deficient diet for 2 weeks. Each group of animals then received a daily oral supplement of the following doses of ascorbic acid: 0.5 mg, 5.0 mg, 50 mg, and 250 mg. All animals were weighed twice a week. Twenty eight days later, a standardized wound was made in the premaxilla. On day 35, all animals were sacrificed. Blood samples were evaluated for levels of ascorbic acid. Thirty nine samples showed insignificant levels of vitamin C, 32 of which showed no ascorbic acid. Organ to body weight ratios were calculated and compared. Spleen to body weight ratios were not affected by different ascorbic acid levels. High levels of ascorbic acid caused a significant increase in adrenal gland to body weight ratios. Varying the levels of ascorbic acid did not affect growth prior to surgical wounding. Increased levels of ascorbic acid enhanced body weight recovery post surgically.

Adrenal Glands↗
PubMed1987

[Effect of ascorbic acid on the intestinal motor activity in domestic animals].

In this paper, the effect of ascorbic acid on motoric activity of the intestines of rabbits, pigs, cows, sheep and horses has been determined, and a possible participation of the adrenogenic system in this mechanism has been shown. In experiments in vitro the motility of the duodeum, jejunum, caecum and colon in the animals mentioned abowe was recorded by the method of Magnus after administration of ascorbic acid. Diastolic reactions were observed in all animals, which were much greater in small intestines than in large ones. To elucidate the diastolic mechanism under the influence of ascorbic acid, it was applied before and after blocking cholinergic and adrenergic receptors in the jejunum of the animals studied. The observed changes in the motility of the intestines seem not to be connected with cholinergic receptors. However, the action of ascorbic acid inhibiting the motility is probably mediated by adrenergic receptors, which was also confirmed by chronic experiments carried out on rabbits. In the farm animals studied the content of ascorbic acid in the wall of the particular intestine segments was determined by the colorimetric method after Roe and Kuenther. A direct proportional relationship was shown between the sensitivity of the intestines to ascorbic acid and its content in the intestine wall. The intestine segments richest in vitamin C showed the highest diastolic reaction under its influence. In control experiments, it was shown that diastolic reactions of the intestines obtained after the application of ascorbic acid were not caused by decreased pH.

Animals↗
PubMed1975

Distribution of ascorbic acid in the ciliary body of albino rabbit, guinea pig and rat.

The distribution of ascorbic acid in the ciliary body has been demonstrated by means of a silver nitrate technique. It appeared that the basal cells in the pars plana region and in the valleys between the ciliary processes contain great amounts of ascorbic acid, in contrast to the basal cells over the processes proper which showed only traces. Rabbit and guinea pig revealed mainly the same findings, and quantitative differences occurred before and after intracardial injection of ascorbic acid. On the other hand, ascorbic acid was absent in the ciliary body of untreated rats, whereas only traces were found after intracardial injection of this substance. These species differences are in keeping with previous reports showing high concentration of ascorbic acid in the aqueous humour from rabbit/guinea pig, and no ascorbic acid at all in aqueous humour from rats.

Animals↗
PubMed1993

Inhibitory effects of ascorbic acid on growth of leukemic and lymphoma cell lines.

Vitamin C has been suggested and disputed as an anti-cancer agent. Previous in vitro studies using either primary cell cultures from cancer patients or tumor cell lines have suggested that tumor cells with different lineages may have different sensitivities to ascorbic acid. In this study we report characterization of the effects of ascorbic acid on growth of two ascorbic acid sensitive and one ascorbic acid resistant lymphocyte tumor cell lines. The cytotoxic effects of ascorbic acid on the sensitive cell lines were time and dosage dependent. Furthermore, the energy state of the ascorbic acid sensitive cells was affected by the presence of ascorbic acid before the cells became apparently non-viable, as demonstrated by 31P nuclear magnetic resonance spectroscopy. The existence of these lymphocyte cell lines with varying sensitivities to ascorbic acid may provide a useful model system for further understanding of vitamin C action on cancer cells.

Adenosine Triphosphate↗
PubMed2004

Short-term ascorbic acid deficiency does not impair antioxidant status in lens of guinea pigs.

We examined whether short-term ascorbic acid deficiency impairs antioxidant status in the lens of guinea pigs. Male guinea pigs aged 4 wk were given a scorbutic diet (20 g/animal per day) with and without ascorbic acid (400 mg/animal per day) in drinking water for 3 wk. The ascorbic acid-deficient group showed no lens opacity. The ascorbic acid-deficient group had 14% of serum ascorbic acid concentration, 6% of aqueous humor ascorbic acid concentration, and 18% of lens ascorbic acid content in the ascorbic acid-adequate group. There were no differences in the contents of lens reduced glutathione and thiobarbituric acid reactive substances, an index of lipid peroxidation, between the ascorbic acid-deficient and adequate groups, while the deficient group had higher lens vitamin E content than the adequate group. The ascorbic acid-deficient group had higher serum vitamin E concentration than the ascorbic acid adequate group, while there were no differences in the concentrations of serum reduced glutathione and tiobarbituric acid reactive substances between the deficient and adequate groups. These results indicate that short-term ascorbic acid deficiency does not impair antioxidant status in the lens of guinea pigs despite induction of severe ascorbic acid depletion in the tissue, which may result in no cataract formation.

Animals↗
PubMed1978

Leucocyte ascorbic acid in Crohn's disease.

Leucocyte ascorbic acid levels have been found to be lower in patients with Crohn's disease than in normal controls. This appears to be due to the disease rather than the effect of drug or operative treatment. Prescribing supplementary ascorbic acid is an appropriate step in correcting this deficiency.

Adult↗
PubMed2004

Role of ascorbic acid in periodontal ligament cell differentiation.

BACKGROUND: Periodontal ligament (PDL) cells form mineralized nodules in vitro. Ascorbic acid is known to be required in this process, although its effect on osteoblastic differentiation of PDL cells remains unclear. The purpose of this study was to determine the role of ascorbic acid on the early osteoblastic differentiation of PDL cells, with regard to alkaline phosphatase (ALP) activity, type I collagen production and integrin expression. METHODS: Cultured PDL cells were stimulated at confluence with ascorbic acid in the presence or absence of type I collagen inhibitor and blocking antibodies to integrins. After stimulation, the cells and culture supernatants were examined for ALP activity, type I collagen production, and integrin expression. The ALP activity was measured using a colorimetric assay with p-nitrophenyl phosphate and ALP staining. Enzyme-linked immunosorbent assay (ELISA) was used to determine type I collagen production, and ELISA and flow cytometric analysis were employed for assessment of integrin expression. RESULTS: Both ALP activity and type I collagen production were upregulated when PDL cells were cultured in the presence of ascorbic acid (200 microM). Inhibitor of the formation of collagen triple helices and blocking antibodies to alpha2beta1 integrin inhibited ALP activity by 50% in ascorbic acid-stimulated PDL cells. Furthermore, ascorbic acid increased the cell surface expression of alpha2beta1 integrin. CONCLUSIONS: Our findings indicated that ascorbic acid increases the ALP activity of PDL cells via type I collagen production and also enhances the expression of alpha2beta1 integrin, which is a major receptor of type I collagen. These results suggest that ascorbic acid promotes the osteoblastic differentiation of PDL cells by modulating type I collagen-alpha2beta1 integrin interaction.

Alkaline Phosphatase↗
PubMed1977

The microspectrophotometric research of the content of ascorbic acid in carcinomas of the uterine cervix.

Taking into consideration the fact that the ascorbic acid takes an active part in the process of growth and reproduction of the cells, the authors have undertook the microspectrophotometric research of its content in 27 different structure cancerous tumours of the uterous cervix. The result of the research showed the decrease of the quantity of ascorbic acid in cancerous tumours of the uterous cervix in compare with norm. The content of ascorbic acid in carcinomas cancerous tumours of the uterine cervix depends on the degree of differentiation and histogenesis of the neoplasm. In less differential squamous cell cancers the quantity of ascorbic acid is more than in the mature ones. The least quantity of ascorbic acid is in adenogenic carcinomas of the uterine cervix. The micro-spectro-photometric research of the content of ascorbic acid in cancerous tumours of the uterine cervix may be used as test in practical activity of the pathologoanatomist for the differential diagnostic and prognosis.

Ascorbic Acid↗
PubMed2005

Antimetastatic effect of a lipophilic ascorbic acid derivative with antioxidation through inhibition of tumor invasion.

PURPOSE: Ascorbic acid (AA), the natural antioxidant, has been demonstrated to exert an antimetastatic action; however, AA is quite unstable in physiological condition. The aim of the present study is to investigate the stability, the antioxidation and the antimetastatic effects of three lipophilic AA derivatives in vitro as well as in vivo. METHODS: The 95D cells were treated with ascorbic acid-2-O-phosphate-6-O-laureate (AA2P6L), ascorbic acid-2-O-phosphate-6-O-myristate (AA2P6M) and ascorbic acid-2-O-phosphate-6-O-stearate (AA2P6S). AA derivatives' stability in medium under cell culture condition, in the presence and in the absence of 95D cells, was assessed by high-performance liquid chromatography assay. Cell viability and intracellular oxidative stress were measured by MTT assay and CDCFH assay, respectively. Wound healing assay and cell adhesion assay were used to investigate the antimetastatic activities against 95D cells in vitro, and the C57BL/6 mice model was used to evaluate the antimetastatic action in vivo. RESULTS: All the three AA derivatives exhibited excellent stability, significantly different from AA. Results of MTT assay showed that IC(50) values of the cytotoxicity of those AA derivatives, namely AA2P6L, AA2P6M and AA2P6S, were 38.46, 28 and 22.97 microg/ml, while the CDCFH assay indicated that EC(50) values of antioxidant effects on 95D cells were 31.12, 33.51 and 38.31 microg/ml, respectively. Through the ratio of IC(50) vs EC(50) for AA derivatives, AA2P6L was demonstrated to be the most effective AA derivative, which retained the antioxidant ability as well as low cytotoxicity. AA2P6L dose-dependently inhibited 95D cells' migration and adhesion, by 50% at the concentration of 20 and 57 microg/ml, respectively. In the animal experiment, intraperitoneal administration of 75 mg/kg AA2P6L decreased the number of metastatic nodules by 62% and elevated the survival rate of C57BL/6 mice about onefold compared to the control group. CONCLUSION: AA2P6L, a lipophilic AA derivative with antioxidation, is shown to be a potent antimetastatic agent through the inhibition of tumor invasion. These results support future investigations on the feasibility of cancer chemotherapy with AA2P6L.

Animals↗
PubMed1987

Differentiation of axon-related Schwann cells in vitro. I. Ascorbic acid regulates basal lamina assembly and myelin formation.

Rat Schwann cells cultured with dorsal root ganglion neurons in a serum-free defined medium fail to ensheathe or myelinate axons or assemble basal laminae. Replacement of defined medium with medium that contains human placental serum (HPS) and chick embryo extract (EE) results in both basal lamina and myelin formation. In the present study, the individual effects of HPS and EE on basal lamina assembly and on myelin formation by Schwann cells cultured with neurons have been examined. Some batches of HPS were unable to promote myelin formation in the absence of EE, as assessed by quantitative evaluation of cultures stained with Sudan black; such HPS also failed to promote basal lamina assembly, as assessed by immunofluorescence using antibodies against laminin, type IV collagen, and heparan sulfate proteoglycan. The addition of EE or L-ascorbic acid with such HPS led to the formation of large quantities of myelin and to the assembly of basal laminae. Pretreatment of EE with ascorbic acid oxidase abolished the EE activity, whereas trypsin did not. Other batches of HPS were found to promote both basal lamina and myelin formation in the absence of either EE or ascorbic acid. Ascorbic acid oxidase treatment or dialysis of these batches of HPS abolished their ability to promote Schwann cell differentiation, whereas the subsequent addition of ascorbic acid restored that ability. Ascorbic acid in the absence of serum was relatively ineffective in promoting either basal lamina or myelin formation. Fetal bovine serum was as effective as HPS in allowing ascorbic acid (and several analogs but not other reducing agents) to manifest its ability to promote Schwann cell differentiation. We suggest that ascorbic acid promotes Schwann cell myelin formation by enabling the Schwann cell to assemble a basal lamina, which is required for complete differentiation.

Animals↗
PubMed1995

In vitro inhibition of human cytomegalovirus replication in human foreskin fibroblasts and endothelial cells by ascorbic acid 2-phosphate.

Antiviral activity of L-ascorbic acid-2-phosphate (ASC-2P), a long-acting derivative of L-ascorbic acid, against several human cytomegalovirus (CMV) strains was examined in cultures of human foreskin fibroblasts (HFF) and endothelial cells (EC). ASC-2P at concentrations ranging from 0.2 to 2 mM had no effect on the number of cells expressing 72 kDa CMV immediate early antigen (IEA) while it inhibited expression of 68 kDa late antigen (LA) in infected cultures of both cell types (30% and 55% reduction for EC and HFF, respectively). In HFF cells, virus yield was reduced up to 4-fold, when ASC-2P was added after CMV infection. Antiviral effects were significantly increased in cultures pretreated with ASC-2P. In HFF and EC pretreated for three subcultures (18 days) with 0.2 mM ASC-2P, a significant reduction of cells expressing IEA (75% and 80% reduction in EC and HFF, respectively) and LA (92% and 90% reduction for EC and HFF, respectively) was observed. Pretreatment for three subcultures with ASC-2P inhibited virus yield 50- to 100-fold in EC and 100- to 1000-fold in HFF. The continuous presence of ASC-2P was not required for its antiviral activity. A significantly higher reduction of virus replication with ganciclovir and foscarnet was obtained in ASC-2P pretreated cells than in untreated controls. The results showed that ASC-2P provides L-ascorbic acid with long-lasting antiviral activity against CMV. ASC-2P may be of benefit for the adjunctive treatment of CMV infection.

Antigens, Viral↗
PubMed2005

Plasma ascorbic acid concentrations and fat distribution in 19,068 British men and women in the European Prospective Investigation into Cancer and Nutrition Norfolk cohort study.

BACKGROUND: Antioxidants, such as ascorbic acid, play a role in scavenging free radicals to protect against oxidative endothelial damage. Excess fat may promote fatty acid oxidation and increase free radical concentrations, which could result in increased antioxidant use. Whether plasma ascorbic acid concentrations are associated with fat distribution remains unclear. OBJECTIVE: Our aim was to examine the association between abdominal obesity, as measured by the waist-to-hip ratio, and plasma ascorbic acid concentrations in the general population. DESIGN: We examined the cross-sectional relation between anthropometric measurements of fat distribution and plasma ascorbic acid concentrations in 19 068 men and women aged 45-79 y without known chronic illness. Dietary ascorbic acid intake was estimated for a subgroup of 8178 men and women who kept 7-d food diaries coded for nutrient intake. RESULTS: The waist-to-hip ratio was inversely related to plasma ascorbic acid concentrations in both men and women. This association was independent of body mass index, age, vitamin supplement use, cigarette smoking, and socioeconomic group. Waist and hip circumferences showed separate and opposite associations with plasma ascorbic acid concentrations, independent of body mass index and other covariates. Dietary ascorbic acid intake only partly explained the observed associations. CONCLUSIONS: Plasma ascorbic acid was associated with fat distribution independent of body mass index. Differences in dietary intake and lifestyle habits, underlying systemic oxidative stress, or both may explain the inverse relation between fat distribution and plasma ascorbic acid concentrations. Additional studies are needed to determine the underlying explanation of these observations.

Abdominal Fat↗
PubMed2003

Ascorbic acid induces a marked conformational change in long duplex DNA.

Ascorbic acid is often regarded as an antioxidant in vivo, where it protects against cancer by scavenging DNA-damaging reactive oxygen species. However, the detailed mechanism of the action of ascorbic acid on genetic DNA is still unclear. We examined the effect of ascorbic acid on the higher-order structure of DNA through real-time observation by fluorescence microscopy. We found that ascorbic acid generates a pearling structure in single giant DNA molecules, with elongated and compact regions coexisting along a molecular chain. Results from electron microscopy and atomic force microscopy indicate that the compact regions assume a loosely packed conformation. A possible mechanism for the induction of this conformational change is discussed in relation to the interplay between the higher-order and second-order structures of DNA.

Ascorbic Acid↗
PubMed1983

NTP Carcinogenesis Bioassay of L-Ascorbic Acid (Vitamin C) (CAS No. 50-81-7) in F344/N Rats and B6C3F1 Mice (Feed Study).

L-Ascorbic acid is essential for many physiologic functions in animals and humans, mostly biochemical reactions involving oxidation. L-Ascorbic acid is approved for use as a dietary supplement and chemical preservative by the U.S. Food and Drug Administration and is on the FDA's list of substances generally recognized as safe. L-Ascorbic acid may be used in soft drinks as an antioxidant for flavor ingredients, in meat and meat-containing products, for curing and pickling, in flour to improve baking quality, in beer as a stabilizer, in fats and oils as an antioxidant, and in a wide variety of foods for vitamin C enrichment. L-Ascorbic acid may also find use in stain removers, hair waving preparations; plastics manufacture, photography, and water treatment. A NTP Carcinogenesis bioassay of L-ascorbic acid (>97% pure) was conducted by administering diets containing 25,000 or 50,000 ppm L-ascorbic acid to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Controls consisted of 50 untreated rats and untreated mice of each sex. Fifty-thousand ppm is the highest dose recommended for chronic studies. Survival of dosed and control female rats and of dosed and control female mice were comparable. Survival of high-dose male rats was slightly greater than that of the controls (P=0.087). Survival of high-dose male mice was significantly greater (P=0.009) than that of the controls. Throughout most of the study, mean body weights of dosed female rats and dosed female mice were lower than those of the controls. Final body weights were comparable among groups, except for the high-dose female rats (<13%); marginal differences (<8%) were observed for low-dose female rats and for dosed female mice (8%-11%). Food consumption was equivalent among groups. Most observational differences were confined to the female rat. The incidence of low-dose female rats with undifferentiated (mononuclear-cell) leukemias (control, 6/50, 12%; low-dose, 17/50, 34%; high-dose, 12/50, 24%) was significantly higher (P<0.02) than that in controls. These tumors were not considered to be related to administration of L-ascorbic acid because they did not occur in the female high-dose group at incidences significantly greater (P>0.07) than those in the controls, the trend test was not significant (P>/=0.07), and no increases were observed for male rats. Under the conditions of this bioassay, L-ascorbic acid was not carcinogenic for male and female F344/N rats or male and female B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative Synonym: vitamin C

Journal Article↗
PubMed2006

Use of an electrochemically etched platinum microelectrode for ascorbic acid mapping in oranges.

A positionable platinum microelectrode fabricated by electrochemical etching was used to monitor the concentration of ascorbic acid in fruits and vegetables. Studies carried out with ascorbate oxidase confirmed the suitability of the amperometric sensor to measure selectively the ascorbic acid content. The results obtained with the proposed method for ascorbic acid determination in orange juices compared well with those found by iodimetry with coulometrically generated iodine. The standard deviation calculated by measuring limiting current values in voltammograms was found to be 3% (n = 150). The sensor allowed the evaluation of the spatial distribution of ascorbic acid concentration in oranges by in-situ measurements. Ascorbic acid concentration maps show that in a perpendicular cut the concentration is higher near the peel to the center of the fruit. In a parallel cut, the concentration increases with the distance to the stem. A correlation between the ripening stage and the ascorbic acid concentration was also observed from electrochemical measurements, the content being higher in mature fruits.

Ascorbic Acid↗
PubMed1993

The influence of maternal nicotine exposure on neonatal lung metabolism. Protective effect of ascorbic acid.

The aim of the present study was to establish whether ascorbic acid supplementation (1 mg/kg/body mass/day) during pregnancy and lactation will prevent the effect of maternal nicotine exposure (1 mg/kg/body weight/day) on neonatal lung carbohydrate, DNA and protein metabolism. The data show that the adult lung ascorbic acid content was reduced by 76% after exposure to nicotine. In contrast, maternal nicotine exposure during pregnancy and lactation has no effect on neonatal lung ascorbic acid content. However, ascorbic acid supplementation during pregnancy and lactation prevented the adverse effects of maternal nicotine exposure on neonatal lung carbohydrate, DNA and protein metabolism.

Animals↗