Chronic Vitamin C Deficiency Promotes Redox Imbalance in the Brain but Does Not Alter Sodium-Dependent Vitamin C Transporter 2 Expression

Paidi, Maya Devi; Schjoldager, Janne G.; Lykkesfeldt, Jens; Tveden‐Nyborg, Pernille

doi:10.3390/nu6051809

Cited by 6 publications

(5 citation statements)

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“…These findings support the notion that renal SVCT1-mediated resorption is crucial for ASC homeostasis. The action of SVCT1 is dose-dependent, and in several tissues, its expression seems to be modulated by ASC concentrations [26]. Although the mechanisms responsible for ASC efflux to plasma are still unclear, volume-sensitive anion channels are conceivably involved [19].…”

Section: Asc Absorptionmentioning

confidence: 99%

Multiple Effects of Ascorbic Acid against Chronic Diseases: Updated Evidence from Preclinical and Clinical Studies

et al. 2020

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Severe disease commonly manifests as a systemic inflammatory process. Inflammation is associated withthe enhanced production of reactive oxygen and nitrogen species and with a marked reduction in the plasma concentrations of protective antioxidant molecules. This imbalance gives rise to oxidative stress, which is greater in patients with more severe conditions such as sepsis, cancer, cardiovascular disease, acute respiratory distress syndrome, and burns. In these patients, oxidative stress can trigger cell, tissue, and organ damage, thus increasing morbidity and mortality. Ascorbic acid (ASC) is a key nutrient thatserves as an antioxidant and a cofactor for numerous enzymatic reactions. However, humans, unlike most mammals, are unable to synthesize it. Consequently, ASC must be obtained through dietary sources, especially fresh fruit and vegetables. The value of administering exogenous micronutrients, to reestablish antioxidant concentrations in patients with severe disease, has been recognized for decades. Despite the suggestion that ASC supplementation may reduce oxidative stress and prevent several chronic conditions, few large, randomized clinical trials have tested it in patients with severe illness. This article reviews the recent literature on the pharmacological profile of ASC and the role of its supplementation in critically ill patients.

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Section: Asc Absorptionmentioning

confidence: 99%

Multiple Effects of Ascorbic Acid against Chronic Diseases: Updated Evidence from Preclinical and Clinical Studies

et al. 2020

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“…Following a persistently low, but non-scorbutic, intake of vitC (100 mgvitC/kg feed), leading to a plasma concentration of 4–5 μM, the brain maintains levels between 100–150 times higher than plasma, compared to a 15–20-fold increase when plasma concentrations are 70 μM [ 67 , 73 ]. The ability to favor vitC levels even during prolonged states of vitC deficiency in the brain is conserved across age groups from early life to young, mature and old guinea pigs [ 24 , 74 , 77 , 78 , 79 ]. This emphasizes a high prioritization of the brain and supports that vitC is pivotal in the brain through all life phases.…”

Section: Vitamin C Transport To the Brainmentioning

confidence: 99%

“…Cultured hippocampal neurons from svct2 −/− mice display reduced growth compared to controls, supporting the essential role of SVCT2 in neuronal development and function [ 93 ]. Surprisingly, vitC depletion and deficiency in vivo is not reflected by an upregulation of the mRNA expression of the SVCT2 transporter in brain tissue, implying that other mechanisms may be crucial in maintaining brain vitC levels [ 67 , 77 , 79 , 97 ].…”

Section: Vitamin C Transport To the Brainmentioning

confidence: 99%

“…Staining of hippocampal sections at PD10 and PD27 showed reduced cell proliferation in the granular layer, but an increase in proliferating cells in the subgranular zone at PD27, suggesting that postnatal cellular migration in hippocampal subdivisions was delayed due to prenatal vitC deficiency [ 74 ]. In guinea pigs, prenatal exposure to vitC deficiency resulted in reduced hippocampal volume until PD70 even though vitC levels and the brain MDA, GSH and ascorbate oxidation ratios were restored after birth, establishing that induced preperinatal or/and perinatal damage persists at least until reproductive maturity [ 74 , 79 ]. There was no reported effects on locomotion, and contrary to previously observed differences in spatial memory [ 185 ], the animals in this study mainly exhibited a random swim pattern in the Morris water maze irrespective of vitC status [ 74 ].…”

Section: Effects Of Vitamin C Deficiency On Brain Developmentmentioning

confidence: 99%

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Vitamin C Deficiency in the Young Brain—Findings from Experimental Animal Models

Tveden‐Nyborg

2021

Nutrients

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Severe and long-term vitamin C deficiency can lead to fatal scurvy, which is fortunately considered rare today. However, a moderate state of vitamin C (vitC) deficiency (hypovitaminosis C)—defined as a plasma concentration below 23 μM—is estimated to affect up to 10% of the population in the Western world, albeit clinical hallmarks in addition to scurvy have not been linked to vitC deficiency. The brain maintains a high vitC content and uniquely high levels during deficiency, supporting vitC’s importance in the brain. Actions include both antioxidant and co-factor functions, rendering vitamin C deficiency likely to affect several targets in the brain, and it could be particularly significant during development where a high cellular metabolism and an immature antioxidant system might increase sensitivity. However, investigations of a non-scorbutic state of vitC deficiency and effects on the developing young brain are scarce. This narrative review provides a comprehensive overview of the complex mechanisms that regulate vitC homeostasis in vivo and in the brain in particular. Functions of vitC in the brain and the potential consequences of deficiency during brain development are highlighted, based primarily on findings from experimental animal models. Perspectives for future investigations of vitC are outlined.

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“…Imbalances in redox status lead to oxidative stress and many pathophysiological disorders including aging and cancer. 10 Tumors have been known to maintain a reduced microenvironment, consequently oxidized and reduced forms of hyperpolarized 13 C-labeled ascorbic acid (vitamin C) have been used as probes to examine tumor redox status. 11 Therefore, vitamin C determination as analyte presents an interesting biological aspect.…”

Section: Introductionmentioning

confidence: 99%

Novel quinoxaline based chemosensors with selective dual mode of action: nucleophilic addition and host–guest type complex formation

et al. 2016

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§ Shared first author(contributed equally) * AbstractNew quinoxalinium salts 1-5 as chemosensors have been exploited via naked eye, UV-Vis absorption, fluorescence quenching and 1 H NMR experiments. New sensors 1-5 showed dual mode, nucleophilic addition and host-guest type complex towards anion (F¯, AcO¯ and ascorbate) detection. Small anions (F¯/AcO¯) showed nucleophilic addition at C2 position of quinoxalinium cation, while larger anion (ascorbate), revealed the formation of host-guest type complex due to steric hindrance posed by C3 of phenyl ring. Nucleophilic addition of small anions (F¯/AcO¯) leads to de-aromatization of quinoxalinium cation. However in the case of larger anion, ascorbate, host-guest type complex formation induces changes in absorption/fluorescence signals of quinoxalinium moiety. This selective binding has been confirmed on the basis of 1 H NMR spectroscopic technique, whereupon nucleophilic addition of small anions (F¯/AcO¯) was confirmed by monitoring characteristic proton NMR signals of H a and methylene protons (CH 2 ), which were clearly shifted in case of fluoride and acetate ions addition confirming de-aromatization and nucleophilic addition. Whereas no such peak shifting was observed in case of ascorbate ion addition confirming non-covalent addition of ascorbate.Theoretical insight into the selectivity and complexation behavior of ascorbate ion with quinoxaline moiety is gained through density functional theory (DFT) calculations. Moreover, the absorption properties of these complexes are modeled theoretically, and compared with the experimental data. In addition, thermal decomposition of sensor (1 and 2) has been studied by the means of differential scanning calorimetry (DSC), thermogravimetry (TG), and differential thermogravimetry (DTG) to signify their utility at variable temperature.

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Chronic Vitamin C Deficiency Promotes Redox Imbalance in the Brain but Does Not Alter Sodium-Dependent Vitamin C Transporter 2 Expression

Cited by 6 publications

References 50 publications

Multiple Effects of Ascorbic Acid against Chronic Diseases: Updated Evidence from Preclinical and Clinical Studies

Multiple Effects of Ascorbic Acid against Chronic Diseases: Updated Evidence from Preclinical and Clinical Studies

Vitamin C Deficiency in the Young Brain—Findings from Experimental Animal Models

Novel quinoxaline based chemosensors with selective dual mode of action: nucleophilic addition and host–guest type complex formation

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