- Human dermal fibroblasts: enhances elastic fiber and collagen deposition via sodium-dependent vitamin C transporters (SVCTs), reduction of intracellular ROS, activation of c-Src kinase, and enhancement of IGF-1 receptor phosphorylation. [1]
- Neuronal T-type calcium channels: selectively inhibits Cav3.2 (α1H) subtype via metal-catalyzed oxidation of histidine 191 in domain I, with no effect on Cav3.1 or Cav3.3. [3]

Sodium ion vitamin C transporter 2 (SVCT-2) is the transporter of L-ascorbic acid and determines its anticancer impact. Based on L-ascorbic acid diet and SVCT-2 expression, L-ascorbic acid (0.1 μM–2 mM) has anticancer effects. The sensitivity of human colorectal cancer cells to L-ascorbic acid varies, primarily based on the degree of SVCT-2 expression [4]. IPSC reprogramming is facilitated by L-ascorbic acid (10 μg) and L-ascorbic acid (50 μg/ml, 5 d) [5]. L-ascorbic acid (50 μg/ml, 9 d) facilitates fibroblast conversion to heart muscle cells[6]. (50 ng/ml, 4-6 d) encourages mice's terminal secretory B cells to develop into totipotent IPS cells[7].

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- Ascorbate (Sodium L-ascorbate) (50–200 μM) significantly stimulated deposition of immuno-detectable elastic fibers and collagen fibers in 72 h cultures of normal human dermal fibroblasts and fat-derived fibroblasts. Higher concentrations (400 μM) did not further stimulate, and 800 μM inhibited elastogenesis. NaCl or a mixture of NaCl and ascorbic acid (AA) had no effect. [1]
- Combination of 100 μM SA with the prolyl hydroxylase inhibitor DMOG inhibited collagen deposition but did not diminish enhanced elastogenesis; 7-day cultures with daily SA showed more elastin, and SA+DMOG further increased elastic fibers and insoluble elastin. [1]
- SA (100 μM) up-regulated tropoelastin mRNA (18 h), intracellular tropoelastin (24 h), and insoluble elastin (72 h). The SVCT inhibitor probenecid (400 μM) eliminated these elastogenic effects. [1]
- SA (100 μM, 2 h) significantly decreased intracellular reactive oxygen species (ROS) levels in fibroblasts, as detected by CM-H₂DCFDA fluorescent probe and flow cytometry. This effect was blocked by probenecid. [1]
- SA enhanced elastogenesis only in cultures with 5% FBS (containing IGF-1). In serum-free medium, SA alone did not induce elastogenesis, but SA enhanced IGF-1-induced tropoelastin synthesis. SA enhanced IGF-1 receptor phosphorylation; this was blocked by c-Src inhibitor PP2 or IGF-1R kinase inhibitor PPP. SA did not enhance insulin receptor phosphorylation. [1]
- In fibroblasts from dermal stretch marks, SA (200 μM) up-regulated collagen and elastic fiber deposition, whereas AA selectively inhibited elastogenesis. [1]
- Ascorbate (ascorbic acid) inhibited native T-type Ca²⁺ currents in acutely dissociated rat dorsal root ganglion (DRG) neurons with an IC₅₀ of 6.5 ± 3.9 μM and maximal inhibition of 70.2 ± 2.1% (Hill coefficient 0.56 ± 0.12). Ascorbate shifted the voltage dependence of activation to more depolarized potentials (V₅₀ from -49.0 to -44.1 mV) and steady-state inactivation to more hyperpolarized potentials (V₅₀ from -75.0 to -80.4 mV), and slowed activation and inactivation kinetics. [3]
- Ascorbate (100–300 μM) reversibly inhibited recombinant human Cav3.2 T-type channels expressed in HEK293 cells, but had no effect on Cav3.1 or Cav3.3 channels. The inhibition was concentration-dependent. [3]
- Site-directed mutagenesis identified histidine 191 (H191) in the extracellular loop between S3 and S4 of domain I as critical for ascorbate sensitivity. Mutations H191Q or H191C abolished ascorbate inhibition. The H191Q mutation also reduced Cu²⁺ sensitivity (>40-fold). [3]
- Ascorbate inhibition was prevented by the metal chelator DTPA, the H₂O₂-decomposing enzyme catalase, and the ROS scavenger c-PTIO. Addition of 300 nM Cu²⁺ increased ascorbate inhibition. [3]

BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. Increased oxidative stress and reduced antioxidant levels are major contributing factors to the development of diabetes and its complications. Therefore, antioxidant supplementation may help control blood glucose levels and delay the onset of diabetic complications. This study aimed to evaluate the effect of L-ascorbic acid (a known antioxidant) on the hypoglycemic activity of tolbutamide in normal and diabetic rats. METHODS: L-ascorbic acid, tolbutamide, or their combination were orally administered to three groups of albino rats of both sexes under normal and diabetic conditions. Diabetes was induced by intraperitoneal injection of alloxan at 100 mg/kg body weight. Blood samples were collected from the retro-orbital plexus at various time intervals, and blood glucose levels were measured using the GOD-POD method. RESULTS: L-ascorbic acid and tolbutamide each produced dose-dependent hypoglycemic effects in both normal and diabetic rats. In the presence of L-ascorbic acid, tolbutamide exhibited an earlier onset of action and a longer duration of effect compared to the tolbutamide-only control group. CONCLUSION: Supplementation with antioxidants such as L-ascorbic acid improves the hypoglycemic response to tolbutamide in normal and diabetic rats. [4]

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The combination of L-ascorbic acid and tolbutamide was designed to cause hypotensive action in both normal (60 mg/kg) and diabetic (40 mg/kg) settings. Tobumide (20 mg/kg) had a longer duration of action and an earlier beginning of action in the presence of L-ascorbic acid when compared to the tolbutamide control [5].

- For elastogenesis studies: Immuno-staining, Western blot, RT-PCR, and quantitative assay of metabolically labeled insoluble elastin using [³H]valine were performed as described. ROS levels were measured using CM-H₂DCFDA fluorescent probe and flow cytometry. [1]
- For T-type calcium channel studies: Whole-cell patch-clamp recordings were performed on acutely dissociated DRG neurons, thalamic slices, and HEK293 cells expressing recombinant channels. External solution contained 10 mM Ba²⁺ as charge carrier. Concentration-response curves were fitted to Hill-Langmuir equation. Voltage dependence of activation and inactivation were fitted to Boltzmann distributions. [3]

- Human dermal fibroblasts and fat-derived fibroblasts (passages 2-4) were cultured in DMEM with 5% FBS. Cells were treated with SA (50–800 μM) for 18–72 h. Immuno-staining for elastin and collagen I, Western blot for tropoelastin, RT-PCR for tropoelastin mRNA, and [³H]valine incorporation for insoluble elastin were performed. [1]
- For ROS measurement, cells were loaded with 10 μM CM-H₂DCFDA for 30 min, then treated with SA (100 μM) for 2 or 24 h, and fluorescence was visualized by microscopy or flow cytometry. [1]
- For IGF-1R phosphorylation studies, cells were lysed and immunoprecipitated with anti-IGF-1R β-subunit antibody, then Western blotted with anti-phosphotyrosine. [1]
- For T-type channel studies: Acutely dissociated rat DRG neurons, thalamic slices, and HEK293 cells transiently expressing Cav3.1, Cav3.2, or Cav3.3 channels were used. Whole-cell voltage-clamp recordings were performed at room temperature. Ascorbate was applied via perfusion. [3]

All animal experiments were performed in accordance with the regulations of the Institutional Animal Ethics Committee. Albino rats of both sexes, weighing 125–175 g, were used in the study. Animals were housed under controlled conditions, 5 per cage, at a temperature of 22±2 °C with a 12-hour light/12-hour dark cycle, and had free access to standard pelleted diet and water. The rats were divided into 3 groups with 5 animals per group. Food was withheld for 18 hours before the experiment, with water available only during this period, and water was withdrawn after the start of the experiment. Blood samples were collected from the retro-orbital plexus of each rat at 0, 0.5, 1, 1.5, 2, 4, and 6 hours after drug administration, and blood glucose levels were determined using the GOD-POD method. Group I received L-ascorbic acid at 60 mg/kg body weight, Group II received tolbutamide at 20 mg/kg body weight, and Group III received L-ascorbic acid at 60 mg/kg body weight prior to tolbutamide administration at 20 mg/kg body weight (normal rats). Since both tolbutamide and vitamin C are administered orally in clinical practice, the oral route was also adopted in this study.[4]

Induction of Diabetes
Albino rats of both sexes weighing 125–175 g were fasted overnight before alloxan injection. Alloxan monohydrate was dissolved in normal saline and injected intraperitoneally at a dose of 100 mg/kg body weight. To counteract early hypoglycemia, animals were orally administered 10% glucose solution. Rats with fasting blood glucose levels above 150 mg/dl were selected for the study. They were divided into 3 groups with 5 animals per group. Group I received L-ascorbic acid at 40 mg/kg body weight, Group II received tolbutamide at 20 mg/kg body weight, and Group III received L-ascorbic acid at 40 mg/kg body weight prior to tolbutamide (20 mg/kg) administration. The dose of L-ascorbic acid was determined based on its hypoglycemic effect producing a response of more than 40%. [4]

Absorption, Distribution and Excretion
70% to 90%
Absorption efficiency depends on the form of the iron salt, the dosage, the administration regimen, and iron reserves. Subjects with normal iron reserves can absorb 10% to 35% of iron supplements. Individuals with iron deficiency can absorb up to 95% of iron supplements.
Ascorbic acid is readily absorbed from the gastrointestinal tract and widely distributed throughout the body. Plasma ascorbic acid concentration increases with increasing intake, reaching a plateau at a daily dose of approximately 90 to 150 mg. Healthy individuals have approximately 1.5 g of ascorbic acid stored in their bodies, but this may be higher with daily intakes exceeding 200 mg. Concentrations in leukocytes and platelets are higher than in erythrocytes and plasma. In deficiency states, the decline in ascorbic acid concentration in leukocytes is later and slower, and is therefore considered a more accurate assessment of ascorbic acid deficiency than plasma concentrations. Ascorbic acid is reversibly oxidized to dehydroascorbic acid; some dehydroascorbic acid is metabolized into inactive ascorbic acid-2-sulfate and oxalic acid, the latter being excreted in urine. Excess ascorbic acid beyond the body's needs is also rapidly excreted unchanged in urine; this usually occurs when daily intake exceeds 100 mg. Ascorbic acid can cross the placenta into breast milk. It can be removed by hemodialysis. The renal threshold for ascorbic acid is approximately 14 μg/mL, but this varies between individuals. When the body reaches ascorbic acid saturation and blood concentration exceeds the threshold, unchanged ascorbic acid is excreted in urine. When tissue saturation and blood ascorbic acid concentration are low, little or no ascorbic acid is excreted in urine after vitamin supplementation. Inactive metabolites of ascorbic acid, such as ascorbic acid-2-sulfate and oxalic acid, are excreted in urine…Ascorbic acid is also excreted in bile, but there is no evidence of enterohepatic circulation…
For more complete data on the absorption, distribution, and excretion of L-ascorbic acid (29 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Hepatic metabolism. Ascorbic acid is reversibly oxidized (by removing hydrogen from the enediol group of ascorbic acid) to dehydroascorbic acid. Both forms present in body fluids are physiologically active. Some ascorbic acid is metabolized into inactive compounds, including ascorbic acid-2-sulfate and oxalic acid.
Ascorbic acid-2-sulfate has been identified as a metabolite of vitamin C in human urine.
Ascorbic acid is oxidized to carbon dioxide in rats and guinea pigs, but the conversion rate is significantly reduced in humans. One metabolic pathway of vitamin C in the human body involves its conversion into oxalic acid, which is ultimately excreted in urine; dehydroascorbic acid may be an intermediate product in this process. Young male guinea pigs were fed diets containing 2 g/kg (18 control animals) or 86 g/kg (29 treatment animals) of ascorbic acid for 275 days. The average weight gain in the control group was significantly higher than that in the treatment group. Eight control animals and eight experimental animals were selected, with similar body weights in both groups. Twenty-four hours before the start of the metabolic study, all animals were fed a diet completely lacking in ascorbic acid. During the metabolic study, 628 g of L-ascorbic acid labeled with 14C was injected intraperitoneally into both the experimental and control groups to study the catabolism and excretion of ascorbic acid. The results showed an increase in the amount of labeled ascorbic acid metabolized into respiratory CO2 in the experimental group guinea pigs. Subsequently, the experimental and control groups were divided into two groups. One group was fed a diet of 3 mg/kg ascorbic acid (chronic deficiency) for 68 days; the other group was fed a diet without ascorbic acid (acute deficiency) for 44 days. Twenty-four hours before the start of the second metabolic study, four control animals and three treatment animals in the chronic deficiency group, and three control animals and four treatment animals in the acute deficiency group, were given a completely ascorbic acid-deficient diet. As described above, (14)C-labeled L-ascorbic acid (628 g) was injected intraperitoneally. Compared with the control animals in the chronic and acute deficiency groups, the treatment animals in the chronic and acute deficiency groups showed an increased amount of labeled ascorbic acid metabolized into respiratory (14)CO2. The levels of radioactive material recovered in urine and feces were similar in both groups, but the excretion of the labeled material in urine was increased in the treatment animals receiving the completely deficient diet. Ascorbic acid storage in tissues was higher in the treatment animals than in the control animals. However, this difference was statistically significant only in the testes. When receiving the completely deficient diet, the treatment animals consumed ascorbic acid at a faster rate than the control animals. Even with vitamin intake below normal levels, the accelerated catabolism could not be reversed… …Hartley guinea pigs, approximately 30 days into gestation, were divided into two groups: a control group receiving 25 mg of ascorbic acid daily, and a treatment group receiving 300 mg/kg of ascorbic acid daily. All animals were fed a diet containing 0.05% ascorbic acid. The two groups were fed their respective diets for 10 days. On day 5 or 10, young mice (both male and female) were randomly selected for metabolic studies. 11-(14)C-ascorbic acid (10 μCurie/mmol) was injected intraperitoneally into the young mice, and they were placed in a metabolic chamber for 5 hours to collect exhaled (14)CO2. From day 11 onwards, all young mice were housed individually and gradually transitioned to a diet containing only trace amounts of ascorbic acid. Animals were checked every three days for signs of scurvy. Once symptoms appeared, animals were examined daily until death. All animals underwent necropsy. Following intraperitoneal injection, the excretion of ¹⁴CO₂ in the treatment group pups increased significantly. The onset of scurvy symptoms in the treatment group pups was 4 days earlier, and death was approximately one week earlier. Correlation analysis between the excretion of labeled carbon dioxide and the date of scurvy symptom onset in both groups revealed a linear correlation, indicating that the earlier onset of scurvy symptoms in the experimental group pups was due to the accelerated rate of ascorbic acid catabolism…
For more complete data on L-ascorbic acid (10 in total), please visit the HSDB record page.
Known human metabolites of ascorbic acid include ascorbic acid-2-sulfate.
Biological half-life
16 days (3.4 hours in individuals with excessive vitamin C levels)
The plasma half-life of ascorbic acid in humans is reported to be 16 days. For individuals with excessive vitamin C levels, the situation is different, with a half-life of 3.4 hours.
The half-life of vitamin C in guinea pigs is 96 hours.
Due to homeostasis, the biological half-life of ascorbic acid varies greatly, ranging from 8 to 40 days, and is inversely proportional to the ascorbic acid content in the body.

Toxicity Summary
Substance Identification: Sources: Ascorbic acid has both natural and synthetic sources. Natural Sources: Ascorbic acid is found in fresh fruits and vegetables. Citrus fruits are excellent sources of ascorbic acid, as are strawberries, acerola cherries, and fresh tea leaves. Ascorbic acid is a colorless, white, or nearly white crystal. It is tasteless or almost tasteless. It has a pleasant sour taste. It is readily soluble in water and slightly soluble in ethanol. It is practically insoluble in ether and chloroform. Human Exposure: Major Risks and Target Organs: The major target organs for toxicity are the gastrointestinal tract, kidneys, and blood system. Clinical Effects Overview: Hemolytic anemia may occur in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency after taking ascorbic acid. Long-term use of high doses may lead to kidney stone formation in individuals prone to kidney stones. In some cases, acute renal failure may occur in both situations. Indications: Prevention and treatment of scurvy. It has been used as a urine acidifier and to correct tyrosinemia caused by a high-protein diet in premature infants. This drug may help treat idiopathic methemoglobinemia. Contraindications: Ascorbic acid is contraindicated in patients with hyperoxaluria and glucose-6-phosphate dehydrogenase deficiency. Route of administration: Oral: Ascorbic acid is usually administered orally in the form of sustained-release capsules, tablets, lozenges, chewable tablets, solutions, and extended-release tablets and capsules. Absorption: Ascorbic acid is readily absorbed after oral administration, but the absorption rate decreases with increasing dose. Gastrointestinal absorption of ascorbic acid may be reduced in patients with diarrhea or gastrointestinal disorders. Distribution by exposure route: The concentration of ascorbic acid in normal plasma is approximately 10 to 20 μg/mL. It is estimated that the total storage of ascorbic acid in the human body is approximately 1.5 g, with a daily turnover of approximately 30 to 45 mg. As the intake dose increases, the plasma concentration of ascorbic acid also increases, reaching a plateau at a daily dose of approximately 90 to 150 mg. Ascorbic acid is widely distributed throughout the body, with higher concentrations in the liver, leukocytes, platelets, glandular tissue, and the lens of the eye. Approximately 25% of ascorbic acid in plasma is bound to proteins. Ascorbic acid can cross the placenta; the concentration in umbilical cord blood is typically 2 to 4 times higher than in maternal blood. Ascorbic acid is also distributed in breast milk. The breast milk of lactating women with a normal diet contains 40 to 70 micrograms per milliliter of ascorbic acid. Biological half-life (by route of exposure): The plasma half-life of ascorbic acid in humans has been reported to be 16 days. However, in individuals with excessively high levels of vitamin C, the half-life is 3.4 hours. Metabolism: Ascorbic acid is reversibly oxidized in the body to dehydroascorbic acid. This reaction occurs by removing a hydrogen atom from the enediol group of ascorbic acid and is part of a hydrogen transfer system. Both forms of ascorbic acid present in bodily fluids are physiologically active. Some ascorbic acid is metabolized into inactive compounds, including ascorbic acid-2-sulfate and oxalate. Excretion (by route of exposure): The renal threshold for ascorbic acid is approximately 14 μg/mL, but this threshold varies from person to person. When the body is saturated with ascorbic acid and the blood concentration exceeds this threshold, unmetabolized ascorbic acid is excreted in the urine. When tissue saturation and blood ascorbic acid concentrations are low, taking this vitamin results in little or no excretion of ascorbic acid in the urine. Inactive metabolites of ascorbic acid, such as ascorbic acid-2-sulfate and oxalate, are excreted in the urine. Ascorbic acid is also excreted via bile, but there is currently no evidence of enterohepatic circulation. Pharmacology and Toxicology: Mechanism of Action: Toxicological Effects: Ascorbic acid intake may lead to hyperoxaluria. Ascorbic acid may cause urine acidification, occasionally resulting in the precipitation of urate, cystine, or oxalate stones or other drugs in the urinary tract. Urinary calcium may increase, and urinary sodium may decrease. Ascorbic acid has been reported to potentially affect glycogenolysis and may have a diabetic effect, but this remains controversial. Pharmacodynamics: In the human body, exogenous ascorbic acid is required for collagen formation and tissue repair. Vitamin C is a cofactor in many biological processes, including the conversion of dopamine to norepinephrine, the hydroxylation step in the synthesis of adrenal steroid hormones, tyrosine metabolism, the conversion of folic acid to folinic acid, carbohydrate metabolism, lipid and protein synthesis, iron metabolism, resistance to infection, and cellular respiration. Vitamin C may act as a free radical scavenger. Toxicity: Human data: Adults: Diarrhea may occur after oral administration of high doses of ascorbic acid. Interactions: Taking more than 200 mg of ascorbic acid with every 300 mg of elemental iron increases gastrointestinal iron absorption. Concomitant use of ascorbic acid and aspirin leads to increased urinary excretion of ascorbic acid and decreased aspirin excretion. Ascorbic acid can prolong the apparent half-life of acetaminophen. It has been reported to interfere with anticoagulation therapy. Carcinogenicity: There is currently no evidence that it is carcinogenic. Some studies suggest that vitamin C may enhance the carcinogenic effects of other substances. L-ascorbic acid can increase the volume of oral cancer induced by dimethylbenzanthracene. Furthermore, butylated hydroxyanisole can induce forestomach cancer in rats. Teratogenicity: There is currently no evidence that it is teratogenic. Mutagenicity: Ascorbic acid has been reported to increase the mutation rate of cultured cells, but this only occurs in cultures with elevated Cu²⁺ or Fe²⁺ concentrations. This effect may be due to the generation of oxygen free radicals induced by ascorbic acid. However, there is currently no evidence that ascorbic acid induces mutations in vivo.

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Effects during pregnancy and lactation
◉ Overview of medication use during lactation
Vitamin C is a normal component of breast milk and an important antioxidant in it. It is recommended that lactating women consume 120 mg of vitamin C daily, and infants aged 6 months and under consume 40 mg daily. Daily intake of high doses of vitamin C, up to 1000 mg, will increase the vitamin C content in breast milk, but this is insufficient to cause health problems for breastfed infants and is not a reason to stop breastfeeding. Breastfeeding women may need vitamin C supplementation to reach the recommended intake or to correct a known vitamin C deficiency. Taking vitamin C during pregnancy at doses at or near the recommended intake will not change the vitamin C content in breast milk. For hospitalized mothers of full-term and premature infants, freezing freshly expressed mature breast milk (at -20°C) for at least 3 months will not change the vitamin C content. After freezing (at -20°C) for 6 to 12 months, the vitamin C content will decrease by 15% to 30%. Storage at -80°C can maintain the vitamin C content for 8 months, after which a 15% loss will occur.
◉ Effects on Breastfed Infants
Sixty healthy lactating women aged 1 to 6 months postpartum who exclusively breastfed their infants received either 500 mg of vitamin C and 100 IU of vitamin E once daily for 30 days, or no supplementation. Infants born to mothers who received vitamin C supplementation showed elevated urinary antioxidant activity biochemical indicators. No clinical outcomes were reported.
Eighteen preterm infants (seven of whom had a gestational age of less than 32 weeks) who were fed mixed, pasteurized donor breast milk starting three days after birth experienced a decrease in mean plasma ascorbic acid concentration from 15.5 mg/L at birth to 5.4 mg/L at 1 week postpartum, and a further decrease to 4.1 mg/L at 3 weeks postpartum. The authors considered the ascorbic acid levels at 1 and 3 weeks to be below therapeutic levels (<6 mg/L), indicating insufficient intake, which may affect postnatal growth and development. Although this study was conducted prior to advancements in parenteral nutrition and enteral fortified milk for preterm infants, contemporary research suggests that insufficient vitamin C intake from mixed pasteurized donor milk may be a potential health problem for preterm infants receiving donor milk.
◉ Effects on lactation and breast milk
No relevant published information found as of the revision date.
Protein binding
25%
Interaction
288 male BALB/c mice were divided into four groups: Group 1 (n=48), control diet; Group 2 (n=48), control diet plus 500 ppm 2-acetaminofluorene (2-AAF); Group 3 (n=96), control diet plus 250 mg/mL ascorbic acid aqueous solution; Group 4 (n=96), control diet, 2-AAF, and ascorbic acid. Food and water consumption was measured weekly. Animals were sacrificed and necropsy performed after 28 days. The addition of ascorbic acid or the interaction between ascorbic acid and 2-AAF did not cause significant differences in relative food consumption. However, the addition of ascorbic acid to drinking water was associated with a significant decrease in relative water intake. The addition of 2-AAF led to a significant increase in relative water intake, and a significant interaction between ascorbic acid and 2-AAF was detected. The main histological changes were limited to the bladder. In the bladders of mice treated with 2-AAF alone or in combination with ascorbic acid, varying degrees of transitional epithelial vacuolation, simple and nodular urothelial hyperplasia, fibrosis, and chronic inflammation of the lamina propria were observed. The lesions were most severe in mice treated with 2-AAF in combination with ascorbic acid. Mice treated with only the control diet and ascorbic acid had normal bladder structure. Chronic inflammation and fibrosis were mainly confined to the bladder base. Increased collagen content, increased angiogenesis, and mononuclear inflammatory cell infiltration were observed in the lamina propria…
Effects of ascorbic acid on metal toxicity.
Table: Effects of Ascorbic Acid on Metal Toxicity [Table #2228]

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Non-human Toxicity Values
Oral LD50 in Rats: 11,900 mg/kg
Oral LD50 in Rats: > 5000 mg/kg body weight / Data from Table/
Subcutaneous LD50 in Rats: 5,000 mg/kg body weight / Data from Table/
Intravenous LD50 in Rats: 1,000 mg/kg body weight / Data from Table/
For more information on the non-human toxicity values (complete data) of L-ascorbic acid (24 items in total), please visit the HSDB record page.

[1]. Aleksander Hinek, et al. Sodium L-ascorbate enhances elastic fibers deposition by fibroblasts from normal and pathologic human skin. J Dermatol Sci. 2014 Sep;75(3):173-82.
[2]. Sungrae Cho, et al. Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression. Sci Rep. 2018 Jul 27;8(1):11372.
[3]. Michael T Nelson, et al. Molecular mechanisms of subtype-specific inhibition of neuronal T-type calcium channels by ascorbate. J Neurosci. 2007 Nov 14;27(46):12577-83.
[4]. Satyanarayana Sreemantula, et al. Influence of antioxidant (L- ascorbic acid) on tolbutamide induced hypoglycaemia/antihyperglycaemia in normal and diabetic rats. BMC Endocr Disord. 2005 Mar 3;5(1):2.
[5]. Sebastian J Padayatty, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003 Feb;22(1):18-35.
[6]. Esteban MA, Wang T, Qin B, et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell. 2010;6(1):71-79. doi:10.1016/j.stem.2009.12.001
[7]. Talkhabi M, Pahlavan S, Aghdami N, Baharvand H. Ascorbic acid promotes the direct conversion of mouse fibroblasts into beating cardiomyocytes. Biochem Biophys Res Commun. 2015;463(4):699-705.
[8]. Stadtfeld M, Apostolou E, Ferrari F, et al. Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells. Nat Genet. 2012;44(4):398-S2.

Therapeutic Uses
Antioxidant; Free radical scavenger. Prevention and treatment of scurvy. In treating patients with thalassemia, 100 to 200 mg of ascorbic acid can be taken daily in combination with deferoxamine to enhance the chelating effect of deferoxamine, thereby increasing iron excretion. In iron-deficient states, ascorbic acid can increase gastrointestinal iron absorption; therefore, some oral iron supplements contain ascorbic acid or ascorbate salts. For more complete data on the therapeutic uses of L-ascorbic acid (30 types), please visit the HSDB record page. Drug Warnings High doses have been reported to cause diarrhea and other gastrointestinal discomfort. High doses of vitamin C have also been reported to potentially lead to hyperoxaluria and the formation of calcium oxalate kidney stones; therefore, vitamin C should be used with caution in patients with hyperoxaluria. Long-term use of high doses of vitamin C may lead to tolerance, resulting in deficiency symptoms when intake is reduced to normal levels. Prolonged or excessive use of chewable vitamin C supplements may cause tooth enamel erosion. High doses of vitamin C can cause hemolysis in patients with G6PD deficiency. Daily intake of 250 mg or more of vitamin C is associated with false-negative results in fecal and gastric occult blood tests. Therefore, to avoid interfering with blood and urine tests, high-dose vitamin C supplements should be discontinued at least two weeks before a physical examination. Vitamin C supplementation may reduce the effectiveness of cancer chemotherapy; its effectiveness in reducing cancer risk and related mortality is unclear. For more complete data on drug warnings for L-ascorbic acid (25 in total), please visit the HSDB records page.

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Pharmacodynamics
Ascorbic acid (vitamin C) is a water-soluble vitamin used to prevent and treat scurvy, as ascorbic acid deficiency leads to scurvy. Collagen structure is primarily affected, and lesions appear in bones and blood vessels. Taking ascorbic acid can completely reverse the symptoms of ascorbic acid deficiency. The main role of iron supplementation is to prevent and treat iron-deficiency anemia. Iron has potential immune-enhancing, anti-cancer, and cognitive-enhancing effects.

C6H8O6

176.12

176.032

C, 40.92; H, 4.58; O, 54.50

50-81-7

L-Ascorbic acid;50-81-7;L-Ascorbic acid sodium salt;134-03-2;L-Ascorbic acid calcium dihydrate;5743-28-2;L-Ascorbic acid;50-81-7

54670067

Crystals (usually plates, sometimes needles, monoclinic system)
White crystals (plates or needles)
White to slightly yellow crystals or powder ... gradually darkens on exposure to light

2.0±0.1 g/cm3

552.7±50.0 °C at 760 mmHg

190-194 °C (dec.)

238.2±23.6 °C

0.0±3.4 mmHg at 25°C

1.711

-2.41

4

6

2

12

232

2

O1C(C(=C([C@@]1([H])[C@]([H])(C([H])([H])O[H])O[H])O[H])O[H])=O

CIWBSHSKHKDKBQ-JLAZNSOCSA-N

InChI=1S/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/t2-,5+/m0/s1

(2R)-2-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2H-furan-5-one

ascorbate; Vitamine C; l-ascorbic acid; ascorbic acid; vitamin C; 50-81-7; L(+)-Ascorbic acid; L-ascorbic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~567.79 mM)
H2O : ≥ 100 mg/mL (~567.79 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)