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PubMed1989

Ascorbic acid in a New World monkey family: species difference and influence of stressors on ascorbic acid metabolism.

Like other simian primates, the New World monkey Callithrix jacchus, marmoset, and Saguinus fuscicollis, tamarin, require ascorbic acid as an essential nutrient. For adult marmosets, a daily intake of 15 mg/kg metabolic body weight was found to be necessary to obtain a serum level above the kidney threshold. A survey of the serum ascorbic acid level of marmosets and tamarins in a breeding colony resulted in a vast divergence between the two species, indicating a higher ascorbic acid requirement for tamarins. Unaccustomed trial conditions or additional stressors resulted in a higher catabolism of ascorbic acid to CO2 in both species, measured with 14C labeled material, compared to a higher rate of renal excretion when the animals were accustomed to the metabolic cage. These isotope excretion studies suggest a different metabolic behavior of ascorbic acid in the two species. This is supposedly caused by a higher sensitivity of the tamarins when subjected to the same conditions as marmosets.

Animals↗
PubMed1984

Structure of ascorbic acid and its biological function. Determination of the conformation of ascorbic acid and isoascorbic acid by infrared and ultraviolet investigations.

The four O-H bands of ascorbic acid could be assigned by means of infrared investigations. It could be shown by electron spin resonance and nuclear magnetic resonance measurements that the radical sodium ascorbate is formed by a cyclic side-chain structure resulting in a loss of C(6)-OH and C(3)-OH. The C(2) = C(3) double bond is still maintained as could be shown by infrared and ultraviolet absorption spectroscopy. In the case of complete oxidation of ascorbic acid to dehydroascorbic acid, C(6)-OH is reestablished (indicating the reopening of the furanoid ring), while C(2)-OH as well as the C(2) = C(3) double bond have disappeared due to the deprotonation of C(2)-OH and C(3)-OH. In the case of isoascorbic acid and its radical potassium isoascorbate similar results are obtained with one distinct difference: in the case of isoascorbic acid, C(2)-OH does not appear while C(3)-OH exhibits a shoulder.

Ascorbic Acid↗
PubMed1969

Studies on the structure of hyaluronic acid. Characterization of the product formed when hyaluronic acid is treated with ascorbic acid.

Physical and chemical methods were used to characterize hyaluronic acid before (fraction HAIIBI) and after (fraction HA-AA) treatment with ascorbic acid. Fraction HA-AA was recovered with an almost quantitative yield and was shown to be chemically identical with fraction HAIIBI by all the methods used. These two materials, however, differed markedly in their molecular sizes and degree of polydispersity. By using sedimentation, diffusion and sedimentation-equilibrium analyses, weight-average molecular weights of about 1.2x10(6) and 6.5x10(4) respectively were obtained for fractions HAIIBI and HA-AA. It is concluded from these results that hyaluronic acid has a molecular weight of about 65000 and that the polysaccharide chain of this molecule is not depolymerized by ascorbic acid. It is further proposed that hyaluronic acid molecules in the matrix of connective tissues are present either in an aggregated form or as subunits of heterogeneous macromolecules, and that it is the linkages responsible for the organization of these structures which are broken by ascorbic acid.

Animals↗
PubMed1977

Effect of PCB (polychlorobiphenyls) on on L-ascorbic acid, pyridoxal phosphate and riboflavin contents in various organs and on hepatic metabolism of L-ascorbic acid in the rat.

Effects of continuous oral administration of PCB (polychlorobiphenyls, 10-100 mg/kg/day, 4 weeks) on tissue levels of L-ascorbic acid (vitamin C), pyridoxal phosphate and riboflavin (vitamin B2) in various organs and on hepatic metabolism of L-ascorbic acid were examined in male Wistar rats weighing 150-250 g. Riboflavin contents in the liver, kidney, brain, heart and testis were not altered by PCB treatments, whereas the hepatic level of pyridoxal phosphate, a biologically active form of vitamin B6, was significantly reduced by PCB administration. Under the same experimental conditions, L-ascorbic acid contents in the liver, kidney, lung and testis showed a significant increase. Histochemical studied revealed that in the adrenal gland, increase of L-ascorbic acid was localized in the fasciculate and reticular zones of cortex, respectively. It was found that increase of L-ascorbic acid in the liver is caused predominantly by activation of biosynthesis at the steps of galactose to D-glucuronic acid and is not due to changes in the catabolic processes of L-ascorbic acid per se. Possible significance of these changes in tissue levels and/or metabolism of vitamins in the occurrence of PCB intoxication is briefly discussed.

Administration, Oral↗
PubMed1975

Ascorbic acid requirements and metabolism in relation to organochlorine pesticides.

Those organochlorine pesticides which possess both high lipoid solubility and high resistance to biodegradation are prone to accumulation in animal tissues and produce relatively long-term effects as toxicants. Such compounds, typified by DDT, Dieldrin, and Lindane, are profound inducers of hepatic microsomal enzymes, including parts of the glucuronic acid and ascorbic acid biosynthetic pathways. Consequently, administering such pesticides to rats in accompanied by enhanced formation and excretion of D-glucuronic acid and L-ascorbic acid, or D-glucaric acid in the case of guinea pigs. Secondarily, the efficiency in biodegrading the pesticides is reduced in ascorbic-acid-deficient guinea pigs with correspondingly greater residue accumulation in tissue. This would aggravate chronic toxic effects of the compounds. Finally, the capacity of the liver to adapt to the presence of such toxicants through enhanced microsomal enzymatic levels appears to be sensitive to its ascorbate status. Impaired enzyme induction is apparent quite early during ascorbic acid depletion in guinea pigs. The enhanced turnover of ascorbate produced by such pesticides, the poor enzymatic adaptation to them during ascorbate depletion and the dependency of the oxidase system upon adequate ascorbate, all point to the central significance of ascorbate status in the liver, and possibly other tissues, as a determinant of their chronic toxicity.

Animals↗
PubMed1992

Absorption of ascorbic acid from a film-coated tablet and from a new enteric-coated pellet preparation in subjects with inadequate plasma levels of ascorbic acid.

The effects of a film-coated tablet and a novel enteric-coated pellet preparation of ascorbic acid (CAS 50-81-7) on the plasma concentration and on the urinary excretion of ascorbic acid were investigated. The pharmacokinetic properties of these dosage forms were also compared both after a single dose and in steady state. The study was carried out as a randomized, single blind parallel group trial in 11 volunteers with inadequate plasma levels of ascorbic acid. The duration of the treatment period was 7 days. After the first dose, higher plasma ascorbic acid concentration as well as AUC and Cmax values were achieved with the film-coated preparation. After the multiple dosing in steady state, plasma ascorbic acid concentration as well as AUC and Cmax values were higher with the new pellet preparation. In addition, the plasma ascorbic acid concentration remained on higher level with pellet preparation on the 7th day. Tmax values for the pellet preparation were also slightly higher on both of the pharmacokinetic test days. The amount of ascorbic acid excreted in urine was higher with the film-coated tablet. According to the results of this study it can be supposed that during the long-term supplementation the more complete absorption can be achieved with the new enteric-coated pellet preparation.

Adult↗
PubMed1990

Plasma cortisol and adrenal ascorbic acid levels after ACTH treatment with a high intake of ascorbic acid in the guinea pig.

The influence of ascorbic acid (AA) intake on plasma cortisol (PC) and tissue AA levels after ACTH treatment was examined using guinea pigs. ACTH produced an 8- to 10-fold rise in PC levels (p less than 0.0001) over the 4-hour experimental period compared to gel-injected control animals. The magnitude of rise in PC was similar at both normal (0.50 g/kg diet) and high (10 g/kg diet) AA intakes. A 30-100% higher (p less than 0.0001) level of AA in tissues (adrenals, liver, and kidneys) and plasma was observed with the high AA diet. ACTH resulted in a 26-30% lower level of AA in the adrenals (p less than 0.0001), but not in other tissues or plasma. PC and adrenal AA responses were unrelated (r = -0.326). These results suggest that ACTH alters AA only in the adrenals, the PC response to and percent decrease in adrenal AA levels with ACTH are not related to AA status, and the absolute level of AA in the adrenals is not critical for steroidogenesis.

Adrenal Glands↗
PubMed1986

Some behavioural and EEG effects of ascorbic acid in rats.

Ascorbic acid (50-200 mg/kg IP) activated gross behaviour and EEG of rats. The behavioural excitation induced by d-amphetamine (2.5 mg/kg SC) was significantly potentiated by ascorbic acid (100-200 mg/kg IP). Catalepsy induced by haloperidol (0.25 mg/kg IP) was attenuated by ascorbic acid (50-200 mg/kg IP) while pentobarbitone (20 mg/kg IP)-induced sleep in rats was dose-dependently antagonised by ascorbic acid (50-400 mg/kg IP). Ascorbic acid (50-400 mg/kg IP) desynchronized the EEG of the frontal cortex and optic cortex while the EMG activity was slightly enhanced in the rat. Ascorbic acid (100 mg/kg IP) potentiated d-amphetamine (2.5 mg/kg SC)-induced EEG desynchronization and EMG activation in the rat. These results indicate that ascorbic acid exerts stimulatory effects in rats. The results also suggest that dopaminergic mechanism may contribute indirectly or directly to the observed behavioural and EEG effects of ascorbic acid.

Animals↗
PubMed1990

Glutathione and ascorbic acid concentrations in the duodenum of rats with cysteamine-induced ulcers: influence of cysteine and ascorbic acid pretreatments.

Duodenal ulceration in rats was induced by a single subcutaneous injection of cysteamine at doses of 7, 28, 42 and 65 mg/100 g body weight 24 h before killing. Duodenal ulceration induced by cysteamine was dose-dependent. However, at 65 mg/100 g body weight, 5 of 6 animals died within 24 h. The concentrations of reduced glutathione (GSH) and ascorbic acid were measured in the duodenal homogenates of cysteamine-treated rats. The ulcerogen, at doses of 28 and 42 mg/100 g body weight, significantly reduced the GSH concentration. At a dose of 28 mg/100 g body weight, however, it did not significantly affect the duodenal ascorbic acid concentration. Pretreatment of rats with daily intramuscular injections of cysteine at 25, 50 and 100 mg/kg or ascorbic acid at 50, 100 and 200 mg/kg for 7 days had no significant effect on the duodenal ulceration produced by cysteamine (28 mg/100 g body weight), although each pretreatment significantly raised the duodenal concentrations of GSH and ascorbic acid respectively, in control rats, and to a lesser extent in cysteamine-treated animals.

Animals↗
PubMed1979

On the possible involvement of ascorbic acid and copper proteins in leukemia. III. ESR investigations on the interaction between ascorbic acid and some transition metal ions.

The interaction between lyophilized samples of ascorbic acid and Cu2+, Fe3+ or Mn2+ has been investigated by means of ESR spectroscopy. All of the three transition metal ions form complexes with vitamin C, but only in the case of Cu2+ and Fe3+ the interaction results in a reduction of the metal ions. Cu2+ and ascorbic acid seem to form 2 : 1 complexes with an equilibrium constant of about K = 1 X 10(7) mol-1. None of these metal ion complexes exhibits, however, the ESR spectrum obtained with leukemic blood.

Ascorbic Acid↗
PubMed1978

Studies on the cholesterol synthesis in the human adipose tissue. II. Mechanism of metabolic shifts and regulation of cholesterol through ascorbic acid.

Ratios of yields of cholesterol in different media with different metabolites (200 estimations) show that if the initial normal quantity in a system is X, glucose makes it 4X which is then reduced by the amino acids and ascorbic acid. Alanine, Serine, Threonine, Cysteine, Cystine and Lysine reduce it to 2X. Glycine, Valine, Leucine, Aspartic, Phenylalanine, Tyrosine, Tryptophan roughly increase it to 6X. Other amino acids are intermediate between the above sets. Balanced amino acids and fatty acids keep up the glucose value 4X but the individual amino acids behave as above. Ascorbic acid reduces the quantity of cholesterol everywhere from one third to one half bringing it back to normal X. Since it is not directly involved in the cholesterol synthesis, it must be acting through the pyridine nucleotides. The interesting feature is that the C/H ratio in the amino acids corresponds to the yield of cholesterol with respect to glucose saline yield = 1. Mechanism of metabolic shifts has been discussed on the empirical basis as also on the basis of the change in ratios of NAD+ (NADP+) to NADH2 (NADPH2) through ascorbic acid.

Acetates↗
PubMed1988

Growth, ascorbic acid and iron contents of tissues of young guinea-pigs whose dams received high or low levels of dietary ascorbic acid or Fe during pregnancy and suckling.

1. Guinea-pig dams were fed on purified diets containing high (5 g/kg diet plus 1 g/l drinking water) or moderate (0.5 g/kg diet) levels of ascorbic acid, in combination with high (1 g/kg diet) or moderate (0.043 g/kg diet) levels of iron, during pregnancy and suckling. Their offsprings' diets contained 0.1 g ascorbic acid/kg and 0.04 g Fe/kg. 2. High ascorbic acid intake clearly enhanced both tissue ascorbate and Fe storage in the dams, and high Fe intake increased both the dams' and the pups' tissue Fe stores. 3. In the animals receiving high Fe intake, a co-existing high ascorbate intake by the dams reduced the growth rate of the offspring, but only during the early stages of development, not during the later stages of post-weaning growth. All the pups' tissue ascorbate levels fell after weaning, but those born of the dams receiving the high ascorbic acid diets did not fall to levels lower than those of the other pups. 4. Thus, although certain disadvantages to the offspring resulting from very-high ascorbic acid intake by pregnant guinea-pig dams were detected, these did not include permanently increased ascorbate requirements, and hence a progression to scurvy as the pups grew and matured.

Animals↗