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PubMed1994

Interactions between hepatic ascorbic acid, cytochrome P-450 and lipids in female guinea pigs with different ascorbic acid intake.

Changes in serum and liver lipids, hepatic ascorbic acid (AA) and cytochrome P-450 were investigated in female guinea pigs divided into three groups with different AA intake in drinking water (10, 100 and 1000 mg AA per liter) for 10 weeks. Serum and liver total cholesterol significantly decreased in guinea pigs receiving 100 and 1000 mg AA per liter of drinking water when compared with guinea pigs with suboptimal AA intake (10 mg/l). Similarly, serum triglycerides were decreased in the groups with higher AA intake. Liver AA concentration increased significantly in accordance with rising AA doses. High AA intake (1000 mg/l) for 10 weeks resulted in significant increase of both cytochromes P-450 and cytochrome b5 and total haeme content in liver microsomes when compared to guinea pigs with suboptimal AA intake. A significant positive correlation between hepatic AA concentration and cytochrome P-450 content was observed. A close negative correlation between liver total cholesterol and cytochrome P-450 content in hepatic microsomes was also seen. Long-term suboptimal AA intake may unfavourably alter the blood and liver lipid profile as well as the capacity of hepatic drug metabolizing enzymes in both male and female guinea pigs.

Animals↗
PubMed1984

Type II epithelial cells of the lung. VII. The effect of ascorbic acid and glutathione.

Ascorbic acid and glutathione deficiencies during the isolation of tissue cells could compromise metabolic functions involving their participation. This possibility was assessed by supplementing the medium used in the isolation of rabbit pulmonary type II cells with varying concentrations and combinations of ascorbic acid, glutathione, and glutathione's constituent amino acids, glutamine, cysteine, and glycine. Isolated type II cells were monitored for changes in their biosynthetic capabilities by examination of 3H-choline and 3H-leucine incorporation into phospholipids and proteins. In the presence of glutathione's constituent amino acids and low concentrations of ascorbic acid (0.056 and 0.56 mM) incorporation of radiolabeled choline and leucine by isolated type II cells was decreased by 50% compared with unsupplemented controls. Morphologic examination revealed that type II cells isolated in the presence of glutathione's constituent amino acids had reduced surface membrane blebbing and dilation of endoplasmic reticulum cisternae compared with unsupplemented controls. Intracellular glutathione levels in these cells was also increased by 100% compared with those isolated without the constituent amino acids. Type II cells isolated in the presence of ascorbic acid and the constituent amino acids attached to culture dishes with a 5-fold greater efficiency compared with unsupplemented controls. The supplementation of type II cell's isolation media with ascorbic acid and glutathione's constituent amino acids produces several beneficial affects possibly through reducing intracellular oxidant damage, although other mechanisms of action cannot be ruled out.

Animals↗
PubMed1995

Ascorbic acid and fertility.

Ascorbic acid has long been associated with fertility, but no consistent study of its mechanism of action in reproductive tissues has been made. This article considers how three of ascorbic acid's principal functions, namely its promotion of collagen synthesis, its role in hormone production, and its ability to protect cells from free radicals, may explain its reproductive actions. Data relating to both ovary and testis are reviewed since ascorbate accumulates in both tissues. Both gonads exhibit cycles of tissue remodeling and of peptide and steroid secretion that can be assumed to be ascorbate-dependent. Ascorbic acid may also prevent gametes from damage by free radicals during production and fertilization. Preliminary data on the concentrations of ascorbic acid in serum and follicular fluid from women undergoing in vitro fertilization are presented. They suggest that the supply of ascorbic acid to the ovary might be a limiting factor in the ability of the preovulatory follicle to grow in response to gonadotropin stimulation. It is concluded that ascorbic acid is a key compound in gonadal physiology on which further research is needed and that a reappraisal of its potential clinical value in the treatment of various types of male and female infertility would be timely.

Animals↗
PubMed1989

Participation of urinary Na+, K+, pH, and L-ascorbic acid in the proliferative response of the bladder epithelium after the oral administration of various salts and/or ascorbic acid to rats.

Changes in urinary parameters (particularly electrolyte levels and pH), and DNA synthesis and the morphology of the bladder epithelium were investigated in rats that were fed for 4 or 8 wk on diets containing various Na, K, Mg or Ca carbonate salts, with or without L-ascorbic acid (AsA). [The carbonate salts were fed at a level of 3% in the diet, and AsA or AsA-Na was administered at 5% in the diet. NH4Cl was at 1% in the diet.] The effects of treatment with NH4Cl (used as a urine acidifier), and of combined treatment with sodium ascorbate (AsA-Na) and NH4Cl were also investigated. Urinary pH was significantly elevated in groups given NaHCO3, K2CO3, AsA + NaHCO3, AsA + K2CO3 and AsA-Na, whereas treatment with AsA or NH4Cl alone caused a significant drop in urinary pH. An increase in urinary electrolytes or ascorbic acid was associated with the corresponding dosing regimen. DNA synthesis in the bladder epithelium was increased in groups given NaHCO3, K2CO3, AsA + NaHCO3, AsA + K2CO3 or AsA-Na. Furthermore, all treatments that induced an elevation of DNA synthesis also induced some morphological alterations in the bladder epithelium. The administration of AsA in conjunction with NaHCO3 or K2CO3 induced levels of change greater than those with either salt alone. In contrast, the degree of response in the bladder epithelium of rats given AsA-Na was reduced by the simultaneous administration of NH4Cl. These results suggest that the degree of DNA synthesis and/or morphological alteration in the rat-bladder epithelium after treatment with various bases may depend on changes in urinary concentrations of Na+ or K+ ions and/or pH, and the presence of ascorbic acid in the urine. The results are discussed in relation to the possible promotion by various treatment regimens (salts +/- AsA) of urinary bladder carcinogenesis.

Administration, Oral↗
PubMed2005

Ascorbic acid supplementation and regular consumption of fresh orange juice increase the ascorbic acid content of human milk: studies in European and African lactating women.

BACKGROUND: Little is known about the influence of an increased intake of ascorbic acid (AA) on human milk AA output. OBJECTIVE: We aimed to compare human milk AA content in European and African women and to evaluate the influence of increased AA intake on human milk AA output. DESIGN: Apparently healthy lactating women were recruited. AA was analyzed by titration with 2,6-dichlorophenol-indophenol. RESULTS: Mean human milk AA was approximately 50% lower (P < 0.001) in the African women (31 mg/kg; n = 171) than in the European women (63 mg/kg; n = 142). AA supplementation (1000 mg/d for 10 d) increased mean human milk AA from 19 to 60 mg/kg (P < 0.001) and from 60 to 70 mg/kg (P = 0.03) in 18 African and 10 European women, respectively. In 11 African women, mean human milk AA increased from 17 to 36 mg/kg (P < 0.001) after intake of 100 mg AA/d for 10 d. In African women, intake of 1 serving of orange juice per week had no significant effect, whereas 3 or 5 servings/wk ( approximately 100 mg AA/serving) for 6 wk increased mean human milk AA from 16 to 32 mg/kg (n = 13) and from 21 to 46 mg/kg (n = 13), respectively (P < 0.001). CONCLUSIONS: Human milk AA can be doubled or tripled by increased intake of AA in women with low human milk AA content at baseline. The response to a relatively high dose of AA was modest in European women in contrast with the 3-fold increase in mean human milk AA content in African women. These data indicate that human milk AA content is regulated.

Adolescent↗
PubMed1995

Resolution of the facilitated transport of dehydroascorbic acid from its intracellular accumulation as ascorbic acid.

We performed a detailed kinetic analysis of the uptake of dehydroascorbic acid by HL-60 cells under experimental conditions that enabled the differentiation of dehydroascorbic acid transport from the intracellular reduction/accumulation of ascorbic acid. Immunoblotting and immunolocalization experiments identified GLUT1 as the main glucose transporter expressed in the HL-60 cells. Kinetic analysis allowed the identification of a single functional activity involved in the transport of dehydroascorbic acid in the HL-60 cells. Transport was inhibited in a competitive manner by both 3-O-methyl-D-glucose and 2-deoxy-D-glucose. In turn, dehydroascorbic acid competitively inhibited the transport of both sugars. A second functional component identified in experiments measuring the accumulation of ascorbic acid appears to be associated with the intracellular reduction of dehydroascorbic acid to ascorbic acid and is not directly involved in the transport of dehydroascorbic acid via GLUT1. Transport of dehydroascorbic acid by HL-60 cells was independent of the presence of external Na+, whereas the intracellular accumulation of ascorbic acid was found to be a Na(+)-sensitive process. Thus, the transport of dehydroascorbic acid via glucose transporters is a Na(+)-independent process which is kinetically and biologically separable from the reduction of dehydroascorbic acid to ascorbic acid and its subsequent intracellular accumulation.

3-O-Methylglucose↗
PubMed1989

Inhibition of paraquat accumulation in rabbit kidney cortex slices by ascorbic acid.

Effects of ascorbic acid and Fe2+ on the accumulation of paraquat into rabbit kidney cortical slices were studied. Ascorbic acid showed dose-dependent inhibition of paraquat accumulation. Fe2+ had a more powerful stimulatory effect on the lipid peroxidation of cortical slices than ascorbic acid, but it did not reduce paraquat accumulation. These results suggest that ascorbic acid is able to inhibit the accumulation of paraquat independent of its peroxidative action, and that ascorbic acid may serve as an antidote for the toxicity of paraquat.

Animals↗
PubMed1979

On the possible involvement of ascorbic acid and copper proteins in leukemia. IV. ESR investigations on the interaction between ascorbic acid and some copper proteins.

The interaction between lyophilized samples of ascorbic acid and some copper proteins (ceruloplasmin, cytochrome-c-oxidase, ascorbate-oxidase) has been investigated by means of ESR spectroscopy. The spectra obtained are identical to the one obtained with leukemic blood. The consequences of this for the molecular events occurring in cancer are discussed. The model proposed can explain the experimental findings reported thus far (such as change in spin concentration with the development of cancer, the presence of a high concentration of antioxidants etc.) as well as reconsile the two existing and seemingly contradictory hypothesis. Possible implications for lipid peroxidation and for the respiratory process are discussed.

Ascorbate Oxidase↗