scholarly journals The Role of Physiological Vitamin C Concentrations on Key Functions of Neutrophils Isolated from Healthy Individuals

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1363 ◽  
Author(s):  
Stephanie M. Bozonet ◽  
Anitra C. Carr
Keyword(s):  
Vitamin C ◽  
Immune Cell ◽  
Dehydroascorbic Acid ◽  
Optimal Level ◽  
Neutrophil Function ◽  
Neutrophil Extracellular Trap ◽  
Healthy Individuals ◽  
Healthy Humans ◽  
Ascorbate Uptake

Vitamin C (ascorbate) is important for neutrophil function and immune health. Studies showing improved immune function have primarily used cells from scorbutic animals or from individuals with infectious conditions or immune cell disorders. Few studies have focused on the requirements of neutrophils from healthy adults. Therefore, we have investigated the role of vitamin C, at concentrations equivalent to those obtained in plasma from oral intakes (i.e., 50–200 µmol/L), on key functions of neutrophils isolated from healthy individuals. Cells were either pre-loaded with dehydroascorbic acid, which is rapidly reduced intracellularly to ascorbate, or the cells were activated in the presence of extracellular ascorbate. We measured the effects of enhanced ascorbate uptake on the essential functions of chemotaxis, oxidant production, programmed cell death and neutrophil extracellular trap (NET) formation. We found that neutrophils isolated from healthy individuals already had replete ascorbate status (0.35 nmol/106 cells), therefore they did not uptake additional ascorbate. However, they readily took up dehydroascorbic acid, thus significantly increasing their intracellular ascorbate concentrations, although this was found to have no additional effect on superoxide production or chemotaxis. Interestingly, extracellular ascorbate appeared to enhance directional mobilityin the presence of the chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP). Stimulation of the cells in the presence of ascorbate significantly increased intracellular ascorbate concentrations and, although this exhibited a non-significant increase in phosphatidylserine exposure, NET formation was significantly attenuated. Our findings demonstrate the ability of neutrophils to regulate their uptake of ascorbate from the plasma of healthy humans to maintain an optimal level within the cell for proper functioning. Higher oral intakes, however, may help reduce tissue damage and inflammatory pathologies associated with NET formation.

scholarly journals Vitamin C and the Role of Citrus Juices as Functional Food

2009 ◽  
Vol 4 (5) ◽  
pp. 1934578X0900400 ◽  
Author(s):  
Nuria Martí ◽  
Pedro Mena ◽  
Jose Antonio Cánovas ◽  
Vicente Micol ◽  
Domingo Saura
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Dehydroascorbic Acid ◽  
Antioxidant Response ◽  
Intestinal Wall ◽  
Processing Temperature ◽  
High Concentration ◽  
Citrus Juices ◽  
Citrus Extract

The literature on the content and stability of vitamin C (ascorbic acid, AA) in citrus juices in relation to industrial practices is reviewed. The role of vitamin C from citrus juices in human diet is also reviewed. Citrus fruits and juices are rich in several types of bioactive compounds. Their antioxidant activity and related benefits derive not only from vitamin C but also from other phytochemicals, mainly flavonoids. During juice processing, temperature and oxygen are the main factors responsible for vitamin C losses. Nonthermal processed juices retain higher levels of vitamin C, but economic factors apparently delay the use of such methods in the citrus industry. Regarding packing material, vitamin C in fruit juice is quite stable when stored in metal or glass containers, whereas juice stored in plastic bottles has a much shorter shelf-life. The limiting step for vitamin C absorption in humans is transcellular active transport across the intestinal wall where AA may be oxidized to dehydroascorbic acid (DHAA), which is easily transported across the cell membrane and immediately reduced back to AA by two major pathways. AA bioavailability in the presence of flavonoids has yielded controversial results. Whereas flavonoids seem to inhibit intestinal absorption of AA, some studies have shown that AA in citrus extract was more available than synthetic ascorbic acid alone. DHAA is reported to possess equivalent biological activity to AA, so recent studies often consider the vitamin C activity in the diet as the sum of AA plus DHAA. However, this claimed equivalence should be carefully reexamined. Humans are one of the few species lacking the enzyme (L-gulonolactone oxidase, GLO) to convert glucose to vitamin C. It has been suggested that this is due to a mutation that provided a survival advantage to early primates, since GLO produces toxic H2O2. Furthermore, the high concentration of AA (and DHAA) in neural tissues could have been the key factor that caused primates (vertebrates with relative big brain) to lose the capacity to synthesize vitamin C. Oxidative damage has many pathological implications in human health, and AA may play a central role in maintaining the metabolic antioxidant response. The abundance of citrus juices in the Mediterranean diet may provide the main dietary source for natural vitamin C.

scholarly journals Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2486
Author(s):  
Ronit Vogt Sionov
Keyword(s):  
Tumor Growth ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Immune Cell ◽  
Neutrophil Function ◽  
The Body ◽  
Cathepsin G ◽  
Metastatic Sites

Neutrophils are the most abundant immune cell in the circulation of human and act as gatekeepers to discard foreign elements that have entered the body. They are essential in initiating immune responses for eliminating invaders, such as microorganisms and alien particles, as well as to act as immune surveyors of cancer cells, especially during the initial stages of carcinogenesis and for eliminating single metastatic cells in the circulation and in the premetastatic organs. Since neutrophils can secrete a whole range of factors stored in their many granules as well as produce reactive oxygen and nitrogen species upon stimulation, neutrophils may directly or indirectly affect carcinogenesis in both the positive and negative directions. An intricate crosstalk between tumor cells, neutrophils, other immune cells and stromal cells in the microenvironment modulates neutrophil function resulting in both anti- and pro-tumor activities. Both the anti-tumor and pro-tumor activities require chemoattraction towards the tumor cells, neutrophil activation and ROS production. Divergence is seen in other neutrophil properties, including differential secretory repertoire and membrane receptor display. Many of the direct effects of neutrophils on tumor growth and metastases are dependent on tight neutrophil–tumor cell interactions. Among them, the neutrophil Mac-1 interaction with tumor ICAM-1 and the neutrophil L-selectin interaction with tumor-cell sialomucins were found to be involved in the neutrophil-mediated capturing of circulating tumor cells resulting in increased metastatic seeding. On the other hand, the anti-tumor function of neutrophils was found to rely on the interaction between tumor-surface-expressed receptor for advanced glycation end products (RAGE) and Cathepsin G expressed on the neutrophil surface. Intriguingly, these two molecules are also involved in the promotion of tumor growth and metastases. RAGE is upregulated during early inflammation-induced carcinogenesis and was found to be important for sustaining tumor growth and homing at metastatic sites. Cathepsin G was found to be essential for neutrophil-supported lung colonization of cancer cells. These data level up the complexity of the dual role of neutrophils in cancer.

Any Role of High-Dose Vitamin C for Septic Shock in 2021?

2021 ◽  
Vol 42 (05) ◽  
pp. 672-682
Author(s):  
Ankita Agarwal ◽  
David N. Hager ◽  
Jonathan E. Sevransky
Keyword(s):  
Septic Shock ◽  
Vitamin C ◽  
Outcome Measures ◽  
Randomized Clinical Trials ◽  
Secondary Outcome ◽  
High Dose ◽  
Healthy Humans ◽  
Vitamin C Supplementation ◽  
High Dose Vitamin

AbstractWhile the use of vitamin C as a therapeutic agent has been investigated since the 1950s, there has been substantial recent interest in the role of vitamin C supplementation in critical illness and particularly, sepsis and septic shock. Humans cannot synthesize vitamin C and rely on exogenous intake to maintain a plasma concentration of approximately 70 to 80 μmol/L. Vitamin C, in healthy humans, is involved with antioxidant function, wound healing, endothelial function, and catecholamine synthesis. Its function in the human body informs the theoretical basis for why vitamin C supplementation may be beneficial in sepsis/septic shock.Critically ill patients can be vitamin C deficient due to low dietary intake, increased metabolic demands, inefficient recycling of vitamin C metabolites, and loss due to renal replacement therapy. Intravenous supplementation is required to achieve supraphysiologic serum levels of vitamin C. While some clinical studies of intravenous vitamin C supplementation in sepsis have shown improvements in secondary outcome measures, none of the randomized clinical trials have shown differences between vitamin C supplementation and standard of care and/or placebo in the primary outcome measures of the trials. There are some ongoing studies of high-dose vitamin C administration in patients with sepsis and coronavirus disease 2019; the majority of evidence so far does not support the routine supplementation of vitamin C in patients with sepsis or septic shock.

scholarly journals Decreased Nuclear Ascorbate Accumulation Accompanied with Altered Genomic Methylation Pattern in Fibroblasts from Arterial Tortuosity Syndrome Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Csilla E. Németh ◽  
Zsófia Nemoda ◽  
Péter Lőw ◽  
Pál Szabó ◽  
Erzsébet Z. Horváth ◽  
...  
Keyword(s):  
Vitamin C ◽  
Epigenetic Regulation ◽  
Dehydroascorbic Acid ◽  
Dna Demethylation ◽  
Nuclear Accumulation ◽  
Specific Gene ◽  
Cultured Fibroblasts ◽  
Arterial Tortuosity ◽  
Arterial Tortuosity Syndrome

Ascorbate requiring Fe2+/2-oxoglutarate-dependent dioxygenases located in the nucleoplasm have been shown to participate in epigenetic regulation of gene expression via histone and DNA demethylation. Transport of dehydroascorbic acid is impaired in the endomembranes of fibroblasts from arterial tortuosity syndrome (ATS) patients, due to the mutation in the gene coding for glucose transporter GLUT10. We hypothesized that altered nuclear ascorbate concentration might be present in ATS fibroblasts, affecting dioxygenase activity and DNA demethylation. Therefore, our aim was to characterize the subcellular distribution of vitamin C, the global and site-specific changes in 5-methylcytosine and 5-hydroxymethylcytosine levels, and the effect of ascorbate supplementation in control and ATS fibroblast cultures. Diminished nuclear accumulation of ascorbate was found in ATS fibroblasts upon ascorbate or dehydroascorbic acid addition. Analyzing DNA samples of cultured fibroblasts from controls and ATS patients, a lower global 5-hydroxymethylcytosine level was found in ATS fibroblasts, which could not be significantly modified by ascorbate addition. Investigation of the (hydroxy)methylation status of specific regions in six candidate genes related to ascorbate metabolism and function showed that ascorbate addition could stimulate hydroxymethylation and active DNA demethylation at the PPAR-γ gene region in control fibroblasts only. The altered DNA hydroxymethylation patterns in patient cells both at the global level and at specific gene regions accompanied with decreased nuclear accumulation of ascorbate suggests the epigenetic role of vitamin C in the pathomechanism of ATS. The present findings represent the first example for the role of vitamin C transport in epigenetic regulation suggesting that ATS is a compartmentalization disease.

scholarly journals The protective role of vitamin C in the management of COVID-19: A Review

2021 ◽  
Vol 96 (1) ◽  
Author(s):  
Mohammad Sarowar Uddin ◽  
Md. Shalahuddin Millat ◽  
Prodip Kumar Baral ◽  
Mahmuda Ferdous ◽  
Md. Giash Uddin ◽  
...  
Keyword(s):  
Vitamin C ◽  
Human Life ◽  
Neutrophil Function ◽  
Protective Role ◽  
Signaling Cascade ◽  
Prevention Strategies ◽  
Main Text ◽  
Oxidative Species ◽  
Potential Therapeutics

Abstract Background The outbreak of coronavirus infectious disease-2019 (COVID-19) is globally deemed a significant threat to human life. Researchers are searching for prevention strategies, mitigation interventions, and potential therapeutics that may reduce the infection’s severity. One such means that is highly being talked in online and in social media is vitamin C. Main text Vitamin C is a robust antioxidant that boosts the immune system of the human body. It helps in normal neutrophil function, scavenging of oxidative species, regeneration of vitamin E, modulation of signaling pathways, activation of pro-inflammatory transcription factors, activation of the signaling cascade, regulation of inflammatory mediators, and phagocytosis and increases neutrophil motility to the site of infection. All of these immunological functions are required for the prevention of COVID-19 infection. Conclusion Considering the role of vitamin C, it would be imperative to administrate vitamin C for the management of severe COVID-19. However, there is no specific clinical data available to confirm the use of vitamin C in the current pandemic.

scholarly journals Role of Lipid, Protein-Derived Toxic Molecules, and Deficiency of Antioxidants behind the Pathogenesis of Diabetic Retinopathy (DR) in Type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Subhasish Pramanik ◽  
Lakshmi Kanta Mondal ◽  
Subhankar Chowdhury ◽  
Chiranjit Bose ◽  
Debgopal Bera ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Vitamin C ◽  
Nadph Oxidase ◽  
Vascular Endothelial ◽  
Healthy Individuals ◽  
Endothelial Growth Factor

To determine the role of NADPH-oxidase mediated formation of different lipid, protein-derived molecules, and depletion of vitamin-C level in vitreous behind the endothelial dysfunction-induced vascular endothelial growth factor secretion and pathogenesis of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Fourteen T2DM patients with mild non-proliferative diabetic retinopathy (MNPDR), 11 patients without diabetic retinopathy (DNR), 17 T2 DM subjects with high-risk proliferative diabetic retinopathy (HRPDR), and 5 healthy individuals without DM underwent vitreous analysis for estimation NADPH oxidase, lipid peroxide like malondialdehyde (MDA), 4-Hydroxy-noneal (HNE) and advanced lipoxidation end product (ALE) like Hexanoyl-lysine (HLY), protein carbonyl compound (PCC), Vitamin-C and concentration of vascular endothelial growth factor (VEGF) secretion following standard spectrophotometric methods and enzyme-linked immunosorbent assay (ELISA). Vitreous concentration of NADPH-oxidase, different protein and lipid-derived molecule, and VEGF were found to be significantly elevated among DNR and of DR subjects with different grades compared to HC subjects whereasthe vitamin-C level was found to be decreased among different DR subjects and DNR subjects in comparison to healthy individuals. Oxidative stress-mediated lipid and protein-derived biomolecules not only add important mediators in the pathogenesis of DR, but also accelerate the progression and severity of microangiopathy.

scholarly journals Vitamin C Recycling Regulates Neurite Growth in Neurospheres Differentiated In Vitro

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1276
Author(s):  
Francisca Espinoza ◽  
Rocío Magdalena ◽  
Natalia Saldivia ◽  
Nery Jara ◽  
Fernando Martínez ◽  
...  
Keyword(s):  
Vitamin C ◽  
Bystander Effect ◽  
High Capacity ◽  
Dehydroascorbic Acid ◽  
Neurite Growth ◽  
Reduced Form ◽  
Incubation Periods ◽  
Neuritic Growth

The reduced form of vitamin C, ascorbic acid (AA), has been related with gene expression and cell differentiation in the cerebral cortex. In neurons, AA is mainly oxidized to dehydroascorbic acid (DHA); however, DHA cannot accumulate intracellularly because it induces metabolic changes and cell death. In this context, it has been proposed that vitamin C recycling via neuron–astrocyte coupling maintains AA levels and prevents DHA parenchymal accumulation. To date, the role of this mechanism during the outgrowth of neurites is unknown. To stimulate neuronal differentiation, adhered neurospheres treated with AA and retinoic acid (RA) were used. Neuritic growth was analyzed by confocal microscopy, and the effect of vitamin C recycling (bystander effect) in vitro was studied using different cells. AA stimulates neuritic growth more efficiently than RA. However, AA is oxidized to DHA in long incubation periods, generating a loss in the formation of neurites. Surprisingly, neurite growth is maintained over time following co-incubation of neurospheres with cells that efficiently capture DHA. In this sense, astrocytes have high capacity to recycle DHA and stimulate the maintenance of neurites. We demonstrated that vitamin C recycling in vitro regulates the morphology of immature neurons during the differentiation and maturation processes.

scholarly journals Neutrophils Isolated from Septic Patients Exhibit Elevated Uptake of Vitamin C and Normal Intracellular Concentrations despite a Low Vitamin C Milieu

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1607
Author(s):  
Anitra C. Carr ◽  
Stephanie Bozonet ◽  
Juliet Pullar ◽  
Emma Spencer ◽  
Patrice Rosengrave ◽  
...  
Keyword(s):  
Vitamin C ◽  
Healthy Volunteers ◽  
Ex Vivo ◽  
Plasma Concentrations ◽  
Dehydroascorbic Acid ◽  
Neutrophil Function ◽  
Healthy Controls ◽  
Lower Plasma ◽  
Circulating Cells ◽  
Plasma Ascorbate

Vitamin C (ascorbate) plays an important role in neutrophil function and is accumulated by the cells either directly via vitamin C transporters (SVCT) or indirectly following oxidation to dehydroascorbic acid. Septic patients are known to have significantly depleted plasma ascorbate status, but little is known about the ascorbate content of their circulating cells. Therefore, we assessed the ascorbate concentrations of plasma, leukocytes and erythrocytes from septic patients and compared these to healthy controls. Non-fasting blood samples were collected from healthy volunteers (n = 20) and critically ill patients with sepsis (n = 18). The ascorbate content of the plasma and isolated neutrophils and erythrocytes was measured using HPLC and plasma myeloperoxidase concentrations were determined using ELISA. Ex vivo uptake of ascorbate and dehydroascorbic acid by neutrophils from septic patients was also assessed. Neutrophils isolated from septic patients had comparable intracellular ascorbate content to healthy volunteers (0.33 vs. 0.35 nmol/106 cells, p > 0.05), despite significantly lower plasma concentrations than the healthy controls (14 vs. 88 µmol/L, p < 0.001). In contrast, erythrocytes from septic patients had significantly lower intracellular ascorbate content than healthy controls (30 vs. 69 µmol/L, p = 0.002), although this was 2.2-fold higher than the matched plasma concentrations in the patients (p = 0.008). Higher concentrations of myeloperoxidase, a source of reactive oxygen species, were observed in the septic patients relative to healthy controls (194 vs. 14 mg/mL, p < 0.0001). In contrast to neutrophils from healthy volunteers, the neutrophils from septic patients demonstrated elevated uptake of extracellular ascorbate. Overall, neutrophils from septic patients exhibited comparable intracellular ascorbate content to those from healthy controls, despite the patients presenting with hypovitaminosis C. The mechanisms involved are currently uncertain, but could include increased generation of dehydroascorbic acid in septic patients, enhanced basal activation of their neutrophils or upregulation of their vitamin C transporters.

Role of vitamin C in gastric cancer

2018 ◽  
Vol 01 (1) ◽  
Author(s):  
Takalkar U Vidyadhar
Keyword(s):  
Gastric Cancer ◽  
Vitamin C ◽  
Gastric Juice ◽  
Oxidative Dna Damage ◽  
Preventive Measure ◽  
Dietary Factors ◽  
Preventive Strategy ◽  
H Pylori

Gastric cancer is a multifactorial disease with complex interplay of environmental and genetic factors. Helicobacter pylori (H. pylori) infestation has been identified as the most important etiological agent in the pathogenesis of gastric cancer. Also, the role of dietary factors that is low consumption of fruits and vegetables have been found to be associated with gastric cancer. Among the dietary factors, antioxidants especially vitamin C has been found to confer the strongest protection against gastric cancer. Its anti-proliferative and pro-apoptotic action has been suggested in vitro. Because of its antioxidant activity, it protects cells against oxidative DNA damage caused by toxic effects of reactive oxygen species. It also inhibits production of carcinogenic N-nitroso compound in the stomach. The person with H. pylori infection has low levels of vitamin C in their gastric juice and levels of vitamin C normalizes on eradication of H. pylori. Vitamin C levels are high in gastric mucosa and gastric juice, sometimes more than that of in plasma. But gastric pathological conditions cause lowered secretion of vitamin C into gastric juice. Effect of H. pylori on vitamin C in gastric juice is reversible and on eradication of H. pylori, it returns to normal level. Hence, eradication of H. pylori and chemoprevention with antioxidant supplementation will be an effective preventive strategy to reduce the incidence of gastric cancer and related mortality. Vitamin C and gastric cancer is an area of potential interest for researchers as a preventive measure. Keywords: Vitamin C, H. pylori, gastric cancer.

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