Mechanism Of Ascorbic Acid Research Articles

Ascorbic acid alleviates rheumatoid arthritis by inhibiting the production of autoantibodies

BackgroundAscorbic acid can regulate the function of the immune system. This study aimed to investigate the underlying mechanisms of ascorbic acid in plasma cell differentiation and rheumatoid arthritis (RA).MethodsMice were intraperitoneally injected with either ascorbic acid or an equivalent volume of phosphate-buffered saline (PBS). To elucidate the effects of ascorbic acid on arthritis, we utilized a collagen induced arthritis mouse model (CIA). To investigate the effects of ascorbic acid on antibody response, mice were immunized with (4-Hydroxy-3-nitrophenylacetyl)-Ficoll (NP-Ficoll) or (4-hydroxy-3-nitrophenyl) acetyl-keyhole limpet hemocyanin (NP-KLH) to elicit a T-cell independent (TI) or T-cell dependent (TD) antibody response. To clarify the ability of ascorbic acid on plasma cell production, we tracked the B cell differentiation fate on the NP-specific B1-8hi BCR transgenic background.ResultsAscorbic acid-injected mice demonstrated significantly delayed disease incidence and decreased disease severity compared to PBS-injected mice. Ascorbic acid can reduce the titers of autoantibodies in both arthritis and lupus mice models. Ascorbic acid can significantly reduce the number of plasma cells and the production of antigen-specific antibodies in TI and TD antibody response. In addition, ascorbic acid can disrupt the antibody affinity maturation. Through B1-8hi adoptive transfer experiments, it has been demonstrated that ascorbic acid restrains B cell differentiation into plasma cells in a cell-intrinsic manner. After in-depth exploration, we found that ascorbic acid can block the cell cycle of B cells and promote cell apoptosis. Mechanistically, ascorbic acid inhibited the production of autoreactive plasma cells by inhibiting the Stat3 signaling pathway.ConclusionOur study demonstrates that ascorbic acid has the ability to suppress the generation of autoreactive plasma cells, diminish the production of autoantibodies, and consequently delay the onset of rheumatoid arthritis.

Inhibitory mechanism of sodium dihydrogen phosphate and ascorbic acid on browning in yellow alkaline noodles

The impacts and mechanisms of ascorbic acid (Vc) and sodium dihydrogen phosphate on the browning of yellow alkaline noodles were investigated. The combination of sodium dihydrogen phosphate and Vc was found to increase the L* value and decreased the number of dark spots, indicating a synergistic anti-browning effect. This combination reduced the activity of polyphenol oxidase (PPO) slightly but deceased the free quinone content significantly (P < 0.05) in noodles. The addition of sodium dihydrogen phosphate also maintained the anti-oxidation stability of Vc, as evidenced by the increased DPPH radical clearance rate in PPO-catechol systems after 24 h of storage. Quantum chemical calculations revealed that sodium dihydrogen phosphate formed hydrogen bonds with ascorbic acid at hydroxyls of carbon-carbon double bond, which protected the ascorbic acid to some degree. This finding suggested that the synergistic anti-browning capacity of sodium dihydrogen phosphate and Vc could be applied to the noodle processing industry.

Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment.

Ascorbic acid has attracted substantial attention for its potential antitumor effects by acting as an antioxidant in vivo and as a cofactor in diverse enzymatic reactions. However, solid proof of its clinical efficacy against cancer and the mechanism behind its effect have not been established. Moreover, cancer forms cancer-specific microenvironments and interacts with various cells, such as cancer-associated fibroblasts (CAFs), to maintain cancer growth and progression; however, the effect of ascorbic acid on the cancer microenvironment is unclear. This review discusses the effects and mechanisms of ascorbic acid on cancer, including the role of ascorbic acid concentration. In addition, we present future perspectives on the effects of ascorbic acid on cancer cells and the CAF microenvironment. Ascorbic acid has a variety of effects, which contributes to the complexity of these effects. Oral administration of ascorbic acid results in low blood concentrations (<0.2 mM) and acts as a cofactor for antioxidant effects, collagen secretion, and HIFα degradation. In contrast, intravenous treatment achieves large blood concentrations (>1 mM) and has oxidative-promoting actions that exert anticancer effects via reactive oxygen species. Therefore, intravenous administration at high concentrations is required to achieve the desired effects on cancer cells during treatment. Partial data on the effect of ascorbic acid on fibroblasts indicate that it may also modulate collagen secretion in CAFs and impart tumor-suppressive effects. Thus, future studies should verify the effect of ascorbic acid on CAFs. The findings of this review can be used to guide further research and clinical trials.

The Anti-Leukemia Effect of Ascorbic Acid: From the Pro-Oxidant Potential to the Epigenetic Role in Acute Myeloid Leukemia.

Data derived from high-throughput sequencing technologies have allowed a deeper understanding of the molecular landscape of Acute Myeloid Leukemia (AML), paving the way for the development of novel therapeutic options, with a higher efficacy and a lower toxicity than conventional chemotherapy. In the antileukemia drug development scenario, ascorbic acid, a natural compound also known as Vitamin C, has emerged for its potential anti-proliferative and pro-apoptotic activities on leukemic cells. However, the role of ascorbic acid (vitamin C) in the treatment of AML has been debated for decades. Mechanistic insight into its role in many biological processes and, especially, in epigenetic regulation has provided the rationale for the use of this agent as a novel anti-leukemia therapy in AML. Acting as a co-factor for 2-oxoglutarate-dependent dioxygenases (2-OGDDs), ascorbic acid is involved in the epigenetic regulations through the control of TET (ten-eleven translocation) enzymes, epigenetic master regulators with a critical role in aberrant hematopoiesis and leukemogenesis. In line with this discovery, great interest has been emerging for the clinical testing of this drug targeting leukemia epigenome. Besides its role in epigenetics, ascorbic acid is also a pivotal regulator of many physiological processes in human, particularly in the antioxidant cellular response, being able to scavenge reactive oxygen species (ROS) to prevent DNA damage and other effects involved in cancer transformation. Thus, for this wide spectrum of biological activities, ascorbic acid possesses some pharmacologic properties attractive for anti-leukemia therapy. The present review outlines the evidence and mechanism of ascorbic acid in leukemogenesis and its therapeutic potential in AML. With the growing evidence derived from the literature on situations in which the use of ascorbate may be beneficial in vitro and in vivo, we will finally discuss how these insights could be included into the rational design of future clinical trials.

Reduction of tellurium (IV) by ascorbic acid in acid perchlorate solutions. A kinetic and mechanistics approach on the nature of electron-transfer process

The kinetics and mechanism of ascorbic acid (AH2) reduction of tellurium (IV) ion in acid perchlorate solutions at a constant ionic strength of 0.1 moldm−3 has been investigated, spectrophotometrically, in terms of the nature of electron-transfer and transition states in the rate-determining step. The experimental observations indicated that the reaction kinetics was of complexity nature. The pseudo-first-order plots were found to be of sigmoidal S-shape nature which indicated the presence of two distinct stages. The initial part of the curves was relatively slow, followed by an increase in the reaction rates at longer time periods. This complicated behavior indicates that the rate-law expression obeys the law-expression (Dt−D∞) = A0e−kst + B0e−kft where ks and kf are corresponding to the observed pseudo-first-order rate constants of the initial induction and final autoacceleration periods, respectively. The experimental results indicated first-order dependence in [AH2] and fractional-first-order kinetics in [Te (IV)] for the initial induction period. The hydrogen ion dependence of the rate constants indicates the oxidation reaction is acid-inhibition with inverse fractional first order in [H+]. A kinetic evidence for formation of 1:1 intermediate complex between the reactants prior to the rate-determining step has been revealed from the Michaelis-Menten relationship. The reaction was found to proceed via free-radical intervention mechanism. The oxidation was found to proceed by one electron-transfer of inner-sphere nature throughout the entire course of reaction. Tellurium (0) of nanoparticle size was synthesized.The ionization constants of tellurium (IV) (H2TeO3) were evaluated at various temperatures, kinetically. The activation parameters and the ionization constant of Te(IV) have been studied at four temperatures. A tentative reaction mechanism consistent with the kinetic data is suggested and discussed.

Ascorbic Acid Promotes the Stemness of Corneal Epithelial Stem/Progenitor Cells and Accelerates Epithelial Wound Healing in the Cornea.

High concentration of ascorbic acid (vitamin C) has been found in corneal epithelium of various species. However, the specific functions and mechanisms of ascorbic acid in the repair of corneal epithelium are not clear. In this study, it was found that ascorbic acid accelerates corneal epithelial wound healing in vivo in mouse. In addition, ascorbic acid enhanced the stemness of cultured mouse corneal epithelial stem/progenitor cells (TKE2) in vitro, as shown by elevated clone formation ability and increased expression of stemness markers (especially p63 and SOX2). The contribution of ascorbic acid on the stemness enhancement was not dependent on the promotion of Akt phosphorylation, as concluded by using Akt inhibitor, nor was the stemness found to be dependent on the regulation of oxidative stress, as seen by the use of two other antioxidants (GMEE and NAC). However, ascorbic acid was found to promote extracellular matrix (ECM) production, and by using two collagen synthesis inhibitors (AzC and CIS), the increased expression of p63 and SOX2 by ascorbic acid was decreased by around 50%, showing that the increased stemness by ascorbic acid can be attributed to its regulation of ECM components. Moreover, the expression of p63 and SOX2 was elevated when TKE2 cells were cultured on collagen I coated plates, a situation that mimics the in vivo situation as collagen I is the main component in the corneal stroma. This study shows direct therapeutic benefits of ascorbic acid on corneal epithelial wound healing and provides new insights into the mechanisms involved. Stem Cells Translational Medicine 2017;6:1356–1365

Ascorbic acid increases demethylation in somatic cell nuclear transfer embryos of the pig (Sus scrofa).

ObjectiveInvestigated the effect and mechanism of ascorbic acid on the development of porcine embryos produced by somatic cell nuclear transfer (SCNT).MethodsPorcine embryos were produced by SCNT and cultured in the presence or absence of ascorbic acid. Ten-eleven translocation 3 (TET3) in oocytes was knocked down by siRNA injection. After ascorbic acid treatment, reprogramming genes were analyzed by realtime reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, relative 5-methylcytosine and 5-hydroxymethylcytosine content in pronucleus were detected by realtime PCR.ResultsAscorbic acid significantly increased the development of porcine embryos produced by SCNT. After SCNT, transcript levels of reprogramming genes, Pou5f1, Sox2, and Klf were significantly increased in blastocysts. Furthermore, ascorbic acid reduced 5-methylcytosine content in pronuclear embryos compared with the control group. Knock down of TET3 in porcine oocytes significantly prevents the demethylation of somatic cell nucleus after SCNT, even if in the presence of ascorbic acid.ConclusionAscorbic acid enhanced the development of porcine SCNT embryos via the increased TET3 mediated demethylation of somatic nucleus.

QSAR Study of the Adsorption Mechanism of Ascorbic Acid towards Iron in Alkaline Media

A significant correlation was obtained between corrosion inhibition efficiency and the molecular structure of ascorbic acid, using the Quantitative Structure Activity Relationship (QSAR) approach based on a multivariate nonlinear regression technique. It is proposed that inhibitor molecules attach to iron surface by means of chemical adsorption. The considerations leading to this assumption were confirmed by ATR FTIR spectroscopy.

Ascorbic acid gives different protective effects in human cells exposed to X-rays and heavy ions

We studied the effects and mechanisms of ascorbic acid as a radiation protector. Cell survival, repair of DNA double strand breaks (DSBs), and sister chromatid exchanges (SCEs) were examined in normal human fibroblasts irradiated with X-rays and heavy ions. Post-irradiation treatment with 5 mM ascorbic acid for 24 h in plateau phase (non-cycling) cells enhanced cell survival and DNA double strand break repair, and reduced SCEs after X-rays irradiation. On the other hand, only reduced SCEs were observed after heavy ion exposure such as to carbon ions. Judging from our data, it is possible that the radioprotective action of ascorbic acid would be effective in non-complex type DNA damage such as induced by X-rays. These findings provide new insight into the mechanism of DNA damage and repair produced by heavy ion irradiation.

Ascorbic Acid in Postoperative Intensive Care Patients - Biochemical Aspects and Clinical Experience

The transport mechanisms of ascorbic acid (AA) are described. The metabolism of AA and its function as an antioxidant are covered in some detail. Subsequently, indications for postoperative substitution are discussed. The supplementation of up to 300 mg of AA per day in postoperative intensive care unit patients during par-/enteral nutrition is recommended to prevent hypovitaminosis. It is not clear if this is the optimal dosage of AA in postoperative/-trauma patients. New aspects for an AA substitution are discussed.

ChemInform Abstract: KINETICS AND MECHANISM OF OXIDATION OF ASCORBIC ACID BY MANGANESE(III) IN AQUEOUS ACIDIC PERCHLORATE MEDIA

The kinetics and mechanism of oxidation of ascorbic acid (H2A) by MnIII in aqueous acidic perchlorate media have been investigated by means of stopped-flow spectrophotometry. The rate law is of the form –½d[MnIII]/dt=(ka+kb[H+]–1)[MnIII][H2A] where the two terms have been assigned to reactions involving the undissociated form of ascorbic acid with Mn3+(aq) and [Mn(OH)]2+(aq) respectively. Comparison with similar reactions involving benzenediols suggests some conclusions on the reduction potentials and the oxidation mechanism of ascorbic acid.