scholarly journals Decreased expression of the vitamin C transporter SVCT1 by ascorbic acid in a human intestinal epithelial cell line

2002 ◽  
Vol 87 (2) ◽  
pp. 97-100 ◽  
Author(s):  
Lauren MacDonald ◽  
Alfred E. Thumser ◽  
Paul Sharp
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Cell Model ◽  
Human Kidney ◽  
The Body ◽  
Epithelial Cell Line ◽  
High Dose ◽  
Acid Uptake ◽  
Cellular Processes ◽  
High Doses

Vitamin C (ascorbic acid) is an essential nutrient that is involved in a number of cellular processes. However, unlike most mammals, man is unable to synthesize vitamin C and it must therefore be acquired from the diet. Absorption of vitamin C is achieved by two transporters, SVCT1 and SVCT2, recently cloned from rat and human kidney. SVCT1 is thought to be the predominant transporter in the intestine. Vitamin C supplements are increasingly common, thus contributing to an increased dietary load, and therefore the aim of the present study was to investigate the effect of high doses of ascorbic acid on SVCT1 expression. Using the Caco-2 TC7 cell model of small intestinal enterocytes, we measured the effects of ascorbic acid (4·5 mg/ml culture medium) on L-[14C]ascorbic acid uptake and SVCT1 expression (determined by reverse transcription-polymerase chain reaction). Ascorbic acid uptake was decreased significantly in Caco-2 TC7 cells exposed to ascorbate for 24 h (-50 %, P<0·0005). Expression of SVCT1 was also significantly reduced by exposure to elevated levels of ascorbate for 24 h (-77 %, P<0·005). Taken together these results suggest that high-dose supplements might not be the most efficient way of increasing the body pool of vitamin C.

scholarly journals Vitamin C In Neuropsychiatry

2015 ◽  
Vol 16 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Dragan M. Pavlović ◽  
Merdin Š. Markišić ◽  
Aleksandra M. Pavlović
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
The Body ◽  
Adult Brain ◽  
Normal Brain ◽  
Positive Effects ◽  
Normal Brain Function ◽  
High Concentrations ◽  
High Doses ◽  
The Brain

Abstract Vitamins are necessary factors in human development and normal brain function. Vitamin C is a hydrosoluble compound that humans cannot produce; therefore, we are completely dependent on food intake for vitamin C. Ascorbic acid is an important antioxidative agent and is present in high concentrations in neurons and is also crucial for collagen synthesis throughout the body. Ascorbic acid has a role in modulating many essential neurotransmitters, enables neurogenesis in adult brain and protects cells against infection. While SVCT1 enables the absorption of vitamin C in the intestine, SVCT2 is primarily located in the brain. Ascorbate deficiency is classically expressed as scurvy, which is lethal if not treated. However, subclinical deficiencies are probably much more frequent. Potential fields of vitamin C therapy are in neurodegenerative, cerebrovascular and affective diseases, cancer, brain trauma and others. For example, there is some data on its positive effects in Alzheimer’s disease. Various dosing regimes are used, but ascorbate is safe, even in high doses for protracted periods. Better designed studies are needed to elucidate all of the potential therapeutic roles of vitamin C.

scholarly journals Unintended Consequence of High-Dose Vitamin C Therapy for an Oncology Patient: Evaluation of Ascorbic Acid Interference With Three Hospital-Use Glucose Meters

2020 ◽  
pp. 193229682093218
Author(s):  
Brooke M. Katzman ◽  
Brandon R. Kelley ◽  
Gayle R. Deobald ◽  
Nikki K. Myhre ◽  
Sean A. Agger ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
High Dose ◽  
Oncology Patient ◽  
Glucose Meter ◽  
High Doses ◽  
The Impact ◽  
Very High ◽  
High Dose Vitamin ◽  
Hospital Use

The use of high-dose vitamin C in cancer care has offered promising results for some patients. However, the intravenous (IV) doses used for these patients can reach concentrations that interfere with some strip-based glucose meters. We characterized the impact of vitamin C interference, from standard to the very high doses used for some cancer protocols, using three different hospital-use glucose meters. For two of the three devices tested, increasing concentrations of ascorbic acid caused false elevations in the glucose measurements. The third glucose meter did not provide inaccurate results, regardless of the vitamin C concentration present. Rather, above a certain threshold, the device generated error messages and no results could be obtained.

scholarly journals The Effect of High Dose Vitamin C (ascorbic acid) on Proinflammatory Cytokines in COVID-19

2021 ◽  
Vol 5 (1) ◽  
pp. 46-50
Author(s):  
MD Ayu Mira Cyntia Dewi
Keyword(s):  
Free Radicals ◽  
Vitamin C ◽  
Proinflammatory Cytokines ◽  
Viral Infections ◽  
Antiviral Drug ◽  
The Body ◽  
High Dose ◽  
Literature Study ◽  
Inflammatory Reactions ◽  
High Doses

Background: COVID-19 is a new pandemic that has claimed many lives in many countries. This pandemic was caused by the SARSCoV2. Until now, there is no specific antiviral drug or vaccine against Covid-19 for potential therapy in humans. This virus can cause cytokine storms which can worsen symptoms in sufferers due to an imbalance between increased oxidant production and available antioxidants. Vitamin C is an important antioxidant that protects the body from various bad effects of free radicals. At high concentrations vitamin C plays an important role in immunomodulation. This study was conducted to determine the effect of high doses of vitamin C on levels of pro-inflammatory cytokines in Covid-19. Method: This research type is literature study. The population in this study were journals about Covid-19, vitamin C, antioxidants and free radicals, inflammatory reactions due to viral infections with samples taken from indexed journals published from 2015 to 2020. There are also clinical trials of high doses of vitamin C against inflammation in Covid-19 from these journals. Results: The results of the study in a clinical trial conducted on 54 patients enrolled in 3 hospitals given a 1: 1 ratio for high-dose intravenous vitamin C (HDIVC) or placebo administration. The HDIVC group received 12 g of vitamin C / 50 ml every 12 hours for 7 days at a rate of 12 ml / hour, and the placebo group received bacteriostatic water for injection in the same way. HDIVC administration showed a reduction in inflammatory markers compared to placebo. Conclusion: The conclusion of this study shows that high doses of vitamin C play a role in reducing levels of proinflammatory cytokines.

scholarly journals Report of the Pilot Study Done for the Proposed Investigation on the Possible Synergic Effect between High-Dose Ascorbic Acid Application and Oncothermia Treatment

2013 ◽  
Vol 2013 ◽  
pp. 1-2
Author(s):  
Csaba Kovago ◽  
Nora Meggyeshazi ◽  
Gabor Andocs ◽  
Andras Szasz
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Internal Control ◽  
Remission Rate ◽  
Treatment Method ◽  
High Dose ◽  
Main Question ◽  
High Doses ◽  
The Right

According to recent investigations, the parenteral application of ascorbic acid (vitamin C) at high doses has significant antitumor activity in in vitro assays. The goal of our experiment was to determine the possible potentiating effect of application of high dose pH-neutralized ascorbic acid to the normal oncothermia treatment method. The NMRI mice were inoculated with C26 murine colon carcinoma cell line subcutaneously at both of their femoral regions and were kept till the tumors reached symmetrically 10 mm in diameter. We created four experimental groups, containing 5 male and 5 female animals in each. Both vitamin-C and oncothermia treatments were applied once; ascorbic acid was applied intra-peritoneally. Oncothermia treatment was applied only to the right limb tumor; the other side will be used as internal control. After the treatment, the animals were sacrificed, and all tumors were removed and analyzed histopathologically. Our main question centers on the comparison of the cell destruction ratio of the various applied treatment regimes, and studies the possible synergy or additive cross-potentiating of the methods. The results of this experiment turned out to be controversial, since the ascorbic acid did not change the remission rate of the allografts and showed no synergy with oncothermia.

scholarly journals APLICAÇÕES CLÍNICAS DA VITAMINA C: UMA BREVE REVISÃO

2021 ◽  
Vol 9 (209) ◽  
pp. 1-15
Author(s):  
Mylena Rafaelle Maciel Guimarães
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Health Risks ◽  
Antioxidant Effect ◽  
The Body ◽  
Pathological State ◽  
Historical View ◽  
Hormone Biosynthesis ◽  
High Doses ◽  
Contemporary Study

Vitamin C or ascorbic acid (AA) is extremely important for humans, as it is not metabolized by the human body, it is necessary to ingest it through diet and / or supplementation. AA has several functions in the body, such as enzymatic cofactors, hormone biosynthesis and antioxidant effect. However, research reports indicate that ingesting high doses of AA may pose health risks. Therefore, the descriptive effect of the clinical application of AA was analyzed. A bibliographic review was carried out and divided into two aspects: the historical view, which was published between 1753 and 2012, and another contemporary study was carried out between 1990 and 2017. The research was carried out on the Academic Google, PubMed, Scielo, Portal de Periódicos da Capes and books, using the keywords: vitamin C, ascorbic acid, antioxidants and pro-oxidants. AA supplements are controversial and their antioxidant and pro-oxidant effects have been described. Its effectiveness in preventing and treating diabetes and cancer is questionable. Therefore, excessive AA supplementation can cause a transition from a healthy to a pathological state, triggering pro-oxidant activity. In addition, the optimal intake dose and the limit between beneficial and harmful doses are still controversial. Therefore, vitamin C should be supplemented with caution and prescribed and supervised by the medical team.

scholarly journals Vitamin C—Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 615
Author(s):  
Martin Doseděl ◽  
Eduard Jirkovský ◽  
Kateřina Macáková ◽  
Lenka Krčmová ◽  
Lenka Javorská ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Iron Absorption ◽  
Plasma Concentrations ◽  
Physiological Role ◽  
Renal Stones ◽  
Anti Oxidant ◽  
High Doses ◽  
Epigenetic Processes

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence—scurvy. The only clinically well-documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is relatively safe, but caution should be given to the administration of high doses, which can cause overt side effects in some susceptible patients (e.g., oxalate renal stones). Lastly, analytical methods for its determination with advantages and pitfalls are also discussed in this review.

scholarly journals High-dose vitamin C enhances cancer immunotherapy

2020 ◽  
Vol 12 (532) ◽  
pp. eaay8707 ◽  
Author(s):  
Alessandro Magrì ◽  
Giovanni Germano ◽  
Annalisa Lorenzato ◽  
Simona Lamba ◽  
Rosaria Chilà ◽  
...  
Keyword(s):  
Immune System ◽  
Vitamin C ◽  
Clinical Evidence ◽  
High Dose ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Mutational Burden ◽  
Cancer Types ◽  
High Doses ◽  
High Dose Vitamin

Vitamin C (VitC) is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its antitumoral efficacy. In addition, whether and how VitC modulates anticancer immune responses is mostly unknown. Here, we show that a fully competent immune system is required to maximize the antiproliferative effect of VitC in breast, colorectal, melanoma, and pancreatic murine tumors. High-dose VitC modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell–dependent manner. VitC not only enhances the cytotoxic activity of adoptively transferred CD8 T cells but also cooperates with immune checkpoint therapy (ICT) in several cancer types. Combination of VitC and ICT can be curative in models of mismatch repair–deficient tumors with high mutational burden. This work provides a rationale for clinical trials combining ICT with high doses of VitC.

scholarly journals Unrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice

2005 ◽  
Vol 79 (1) ◽  
pp. 214-224 ◽  
Author(s):  
Hiroyuki Nakai ◽  
Sally Fuess ◽  
Theresa A. Storm ◽  
Shin-ichi Muramatsu ◽  
Yuko Nara ◽  
...  
Keyword(s):  
Portal Vein ◽  
Dose Response ◽  
Smooth Muscles ◽  
The Body ◽  
Specific Gene ◽  
High Dose ◽  
Adeno Associated Virus ◽  
Virus Serotype ◽  
High Doses ◽  
Dose Response Study

ABSTRACT Recombinant adeno-associated virus (rAAV) vectors can mediate long-term stable transduction in various target tissues. However, with rAAV serotype 2 (rAAV2) vectors, liver transduction is confined to only a small portion of hepatocytes even after administration of extremely high vector doses. In order to investigate whether rAAV vectors of other serotypes exhibit similar restricted liver transduction, we performed a dose-response study by injecting mice with β-galactosidase-expressing rAAV1 and rAAV8 vectors via the portal vein. The rAAV1 vector showed a blunted dose-response similar to that of rAAV2 at high doses, while the rAAV8 vector dose-response remained unchanged at any dose and ultimately could transduce all the hepatocytes at a dose of 7.2 × 1012 vector genomes/mouse without toxicity. This indicates that all hepatocytes have the ability to process incoming single-stranded vector genomes into duplex DNA. A single tail vein injection of the rAAV8 vector was as efficient as portal vein injection at any dose. In addition, intravascular administration of the rAAV8 vector at a high dose transduced all the skeletal muscles throughout the body, including the diaphragm, the entire cardiac muscle, and substantial numbers of cells in the pancreas, smooth muscles, and brain. Thus, rAAV8 is a robust vector for gene transfer to the liver and provides a promising research tool for delivering genes to various target organs. In addition, the rAAV8 vector may offer a potential therapeutic agent for various diseases affecting nonhepatic tissues, but great caution is required for vector spillover and tight control of tissue-specific gene expression.

scholarly journals Dehydroascorbic acid uptake in a human keratinocyte cell line (HaCaT) is glutathione-independent

2000 ◽  
Vol 345 (3) ◽  
pp. 665-672 ◽  
Author(s):  
Isabella SAVINI ◽  
Sylvie DUFLOT ◽  
Luciana AVIGLIANO
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Reductase Activity ◽  
Thioredoxin Reductase ◽  
Dehydroascorbic Acid ◽  
Reduction Process ◽  
Enzymic Activity ◽  
Glutathione Depletion ◽  
Acid Uptake ◽  
Hacat Cells

Vitamin C plays an important role in neutralizing toxic free radicals formed during oxidative metabolism or UV exposure of human skin. This study was performed to investigate the mechanisms that regulate the homoeostasis of vitamin C in HaCaT cells by identifying the events involved in the transport and in the reduction of dehydroascorbic acid. Dehydroascorbic acid accumulated to a greater extent and faster compared with ascorbic acid; its transport appeared to be mediated by hexose transporters and was entirely distinct from ascorbic acid transport. Dehydroascorbate reductase activity was unaffected by glutathione depletion, although it was sensitive to thiol protein reagents. These observations, as well as the subcellular distribution of this enzymic activity and the cofactor specificity, indicate that thioredoxin reductase and lipoamide dehydrogenase play an important role in this reduction process. HaCaT cells were able to enhance their dehydroascorbic acid reductase activity in response to oxidative stress.

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