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International Journal of Molecular... May 2020Ascorbic acid (AscH) is one of the most important vitamins found in the human diet, with many biological functions including antioxidant, chelating, and coenzyme...
Ascorbic acid (AscH) is one of the most important vitamins found in the human diet, with many biological functions including antioxidant, chelating, and coenzyme activities. Ascorbic acid is also widely used in a medical practice especially for increasing the iron absorption and as an adjuvant therapeutic in the iron chelation therapy, but its mode of action and implications in the iron metabolism and toxicity are not yet clear. In this study, we used UV-Vis spectrophotometry, NMR spectroscopy, and EPR spin trapping spectroscopy to investigate the antioxidant/pro-oxidant effects of ascorbic acid in reactions involving iron and the iron chelator deferiprone (L1). The experiments were carried out in a weak acidic (pH from 3 to 5) and neutral (pH 7.4) medium. Ascorbic acid exhibits predominantly pro-oxidant activity by reducing Fe to Fe, followed by the formation of dehydroascorbic acid. As a result, ascorbic acid accelerates the redox cycle Fe ↔ Fe in the Fenton reaction, which leads to a significant increase in the yield of toxic hydroxyl radicals. The analysis of the experimental data suggests that despite a much lower stability constant of the iron-ascorbate complex compared to the FeL1 complex, ascorbic acid at high concentrations is able to substitute L1 in the FeL1 chelate complex resulting in the formation of mixed L1AscFe complex. This mixed chelate complex is redox stable at neutral pH = 7.4, but decomposes at pH = 4-5 during several minutes at sub-millimolar concentrations of ascorbic acid. The proposed mechanisms play a significant role in understanding the mechanism of action, pharmacological, therapeutic, and toxic effects of the interaction of ascorbic acid iron, and L1.
Topics: Ascorbic Acid; Chelating Agents; Deferiprone; Electron Spin Resonance Spectroscopy; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxyl Radical; Iron; Iron Chelating Agents; Magnetic Resonance Spectroscopy; Oxidants; Oxidation-Reduction; Oxygen; Reactive Oxygen Species; Spectrophotometry, Ultraviolet
PubMed: 32486511
DOI: 10.3390/ijms21113967 -
Frontiers in Chemistry 2022L-Ascorbic acid (ASC), commonly known as vitamin C, acts as an anti-oxidant in the biological system. It is extensively used as an excipient in pharmaceutical industry,...
L-Ascorbic acid (ASC), commonly known as vitamin C, acts as an anti-oxidant in the biological system. It is extensively used as an excipient in pharmaceutical industry, food supplements in fruit juices, and food materials due to its free radicals scavenging activity. Main drawback of ASC is its poor aqueous stability owing to the presence of lactone moiety that is easily oxidized to dehydroascorbic acid and further degraded. To improve aqueous stability and inhibit oxidative degradation, ASC was co-crystallized to constitute binary eutectic compositions with mono and di-saccharides such as glucose, sucrose, lactose, and mannitol. The eutectics were confirmed by their (single) lower melting endotherm compared to ASC and sugars, although Powder X-ray diffraction (PXRD) and Fourier transform Infrared spectroscopy (FT-IR) data confirmed the characteristics of their physical mixture. Scanning electron microscope (SEM) images of the binary eutectics confirmed their irregular morphology. The ASC eutectics exhibited improved shelf-life by 2-5-fold in weakly acidic (pH 5) and neutral (pH 7) aqueous buffer medium, whereas the eutectic with glucose enhanced shelf-life only by 1.1-1.2-fold in acidic medium (pH 3.3 and 4). Notably, stabilizing effect of the sugar eutectics decreased with increasing acidity of the medium. In addition, higher binding energy of the disaccharide eutectics partially supports the aqueous stability order of ASC in the neutral pH medium due to more number of non-bonded interactions than that of monosaccharides.
PubMed: 35615307
DOI: 10.3389/fchem.2022.754269 -
Dissection of NSY50-Induced Defense in Cucumber Roots against f. sp. by Target Metabolite Profiling.Biology Jul 2022To gain insights into the roles of beneficial PGPR in controlling soil-borne disease, we adopted a metabolomics approach to investigate the beneficial impacts of NSY50...
To gain insights into the roles of beneficial PGPR in controlling soil-borne disease, we adopted a metabolomics approach to investigate the beneficial impacts of NSY50 on cucumber seedling roots under the pathogen of f. sp. (FOC). We found that NSY50 pretreatment (NSY50 + FOC) obviously reduced the production of reactive oxygen species (ROS). Untargeted metabolomic analysis revealed that 106 metabolites responded to NSY50 and/or FOC inoculation. Under FOC stress, the contents of root osmotic adjustment substances, such as proline and betaine were significantly increased, and dehydroascorbic acid and oxidized glutathione (GSH) considerably accumulated. Furthermore, the contents of free amino acids such as tryptophan, phenylalanine, and glutamic acid were also significantly accumulated under FOC stress. Similarly, FOC stress adversely affected glycolysis and the tricarboxylic acid cycles and transferred to the pentose phosphate pathway. Conversely, NSY50 + FOC better promoted the accumulation of α-ketoglutaric acid, ribulose-5-phosphate, and 7-phosphosodiheptanone compared to FOC alone. Furthermore, NSY50 + FOC activated GSH metabolism and increased GSH synthesis and metabolism-related enzyme activity and their encoding gene expressions, which may have improved redox homoeostasis, energy flow, and defense ability. Our results provide a novel perspective to understanding the function of NSY50, accelerating the application of this beneficial PGPR in sustainable agricultural practices.
PubMed: 36101409
DOI: 10.3390/biology11071028 -
Stem Cell Research & Therapy Jan 2024After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to myocardial dysfunction. Direct reprogramming of...
BACKGROUND
After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to myocardial dysfunction. Direct reprogramming of fibroblasts into cardiomyocytes via the forced overexpression of cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) offers a promising strategy for cardiac repair. The limited reprogramming efficiency of this approach, however, remains a significant challenge.
METHODS
We screened seven factors capable of improving direct cardiac reprogramming of both mice and human fibroblasts by evaluating small molecules known to be involved in cardiomyocyte differentiation or promoting human-induced pluripotent stem cell reprogramming.
RESULTS
We found that vitamin C (VitC) significantly increased cardiac reprogramming efficiency when added to GMT-overexpressing fibroblasts from human and mice in 2D and 3D model. We observed a significant increase in reactive oxygen species (ROS) generation in human and mice fibroblasts upon Doxy induction, and ROS generation was subsequently reduced upon VitC treatment, associated with increased reprogramming efficiency. However, upon treatment with dehydroascorbic acid, a structural analog of VitC but lacking antioxidant properties, no difference in reprogramming efficiency was observed, suggesting that the effect of VitC in enhancing cardiac reprogramming is partly dependent of its antioxidant properties.
CONCLUSIONS
Our findings demonstrate that VitC supplementation significantly enhances the efficiency of cardiac reprogramming, partially by suppressing ROS production in the presence of GMT.
Topics: Humans; Mice; Animals; Reactive Oxygen Species; Ascorbic Acid; Antioxidants; Cellular Reprogramming; T-Box Domain Proteins; MEF2 Transcription Factors; Myocytes, Cardiac; Vitamins; Fibroblasts
PubMed: 38229180
DOI: 10.1186/s13287-023-03615-x -
International Journal of Molecular... Nov 2019Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to treat. Meldonium is an anti-ischemic agent that shifts energy production...
Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our results showed that meldonium decreased animal body mass gain, food and water intake, and carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1, causing manganese superoxide dismutase expression and activity to increase, as well as lipid peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex changes in renal lipidomics. Taken together, our results have confirmed that meldonium pre-treatment protects against I/R-induced oxidative stress and apoptosis/necrosis.
Topics: Acute Kidney Injury; Animals; Inflammation; Kidney; Male; Methylhydrazines; Norepinephrine; Oxidative Stress; Phosphorylation; Rats; Rats, Wistar; Reperfusion Injury
PubMed: 31731785
DOI: 10.3390/ijms20225747 -
Advanced Healthcare Materials Jan 2023Due to the deficient catalase, abundant reduced iron and low acidic environment in lysosomes, inducing lysosomal membrane permeabilization (LMP) through Fenton...
Due to the deficient catalase, abundant reduced iron and low acidic environment in lysosomes, inducing lysosomal membrane permeabilization (LMP) through Fenton reaction-based reactive oxygen species (ROS) generation recently attracts increasing attention in cancer therapy. However, the lysosomal membranes are protected by highly glycosylated membrane proteins and several endolysosomal damage-response mechanisms can rapidly repair the injured lysosomes. To produce sufficient ROS and cause complete lysosomal membranes rupture, a lysosome-targeted ROS inducer, N-(3-Aminopropyl) morpholine grafted cross-linked lipoic acid vesicles with vitamin C-loading (VC@ cLAVs), is developed. VC@ cLAVs efficiently accumulate in lysosomes and convert into two redox couples LA/DHLA (dihydrolipoic acid, reduced form of LA) and VC/DHA (dehydroascorbic acid, oxidized form of VC) by the lysosomal glutathione, which can not only produce a large amount of H O by pro-oxidant action but also accelerate iron transformation through the cyclic redox reactions between each other and cause the efficient conversion of the generated H O into highly toxic •OH. Both in vitro and in vivo experiments demonstrate that VC@ cLAVs can effectively enhance ROS production and boost LMP, finally initiation irreversible death of tumor cells via ferroptosis pathway, thus representing a potential anticancer drug for cancer therapy.
Topics: Humans; Reactive Oxygen Species; Ferroptosis; Neoplasms; Lysosomes; Iron
PubMed: 36408929
DOI: 10.1002/adhm.202202150 -
BMC Plant Biology Sep 2023Salt stress is one of the key factors limiting rice production. Alginate oligosaccharides (AOS) enhance plant stress resistance. However, the molecular mechanism...
BACKGROUND
Salt stress is one of the key factors limiting rice production. Alginate oligosaccharides (AOS) enhance plant stress resistance. However, the molecular mechanism underlying salt tolerance in rice induced by AOS remains unclear. FL478, which is a salt-tolerant indica recombinant inbred line and IR29, a salt-sensitive rice cultivar, were used to comprehensively analyze the effects of AOS sprayed on leaves in terms of transcriptomic and metabolite profiles of rice seedlings under salt stress.
RESULTS
In this experiment, exogenous application of AOS increased SOD, CAT and APX activities, as well as GSH and ASA levels to reduce the damage to leaf membrane, increased rice stem diameter, the number of root tips, aboveground and subterranean biomass, and improved rice salt tolerance. Comparative transcriptomic analyses showed that the regulation of AOS combined with salt treatment induced the differential expression of 305 and 1030 genes in FL478 and IR29. The expressed genes enriched in KEGG pathway analysis were associated with antioxidant levels, photosynthesis, cell wall synthesis, and signal transduction. The genes associated with light-trapping proteins and RLCK receptor cytoplasmic kinases, including CBA, LHCB, and Lhcp genes, were fregulated in response to salt stress. Treatment with AOS combined with salt induced the differential expression of 22 and 50 metabolites in FL478 and IR29. These metabolites were mainly related to the metabolism of amino and nucleotide sugars, tryptophan, histidine, and β -alanine. The abundance of metabolites associated with antioxidant activity, such as 6-hydroxymelatonin, wedelolactone and L-histidine increased significantly. Combined transcriptomic and metabolomic analyses revealed that dehydroascorbic acid in the glutathione and ascorbic acid cycles plays a vital role in salt tolerance mediated by AOS.
CONCLUSION
AOS activate signal transduction, regulate photosynthesis, cell wall formation, and multiple antioxidant pathways in response to salt stress. This study provides a molecular basis for the alleviation of salt stress-induced damage by AOS in rice.
Topics: Transcriptome; Seedlings; Antioxidants; Oryza; Salt Stress; Glutathione; Oligosaccharides
PubMed: 37770835
DOI: 10.1186/s12870-023-04470-x -
International Journal of Molecular... Dec 2022is one of the precious tree species in northeast China and has important economic and ecological value. Ascorbic acid (ASA) is a strong antioxidant that can...
is one of the precious tree species in northeast China and has important economic and ecological value. Ascorbic acid (ASA) is a strong antioxidant that can significantly improve plant photosynthetic efficiency and stress resistance and participate widely in plant growth and development. In this study, we investigated the development process of mature zygotic embryos of under different concentrations of ASA and found that 100 mg·L exogenous ASA was the optimal concentration and that the induction rate of somatic embryos (SEs) was the highest at 72.89%, which was 7.13 times higher than that of the control group. The polyphenol content, peroxidase (POD) activity, nitric oxide (NO) content, nitrate reductase (NR) activity, total ascorbic acid (T-ASA) content, ASA content, ASA/Dehydroascorbic acid (DHA) ratio, GSH/GSSG ratio, and ascorbate peroxidase (APX) activity were significantly increased under the application of exogenous ASA in explants, whereas the polyphenol oxidase (PPO) activity, phenylalanine ammonia-lyase (PAL) activity, superoxide dismutase (SOD) activity, and catalase (CAT) activity, malondialdehyde (MDA) content and nitric oxide synthase (NOS) activity were decreased. At the same time, the content of T-ASA and ASA, T-GSH and GSSG, and PAL and SOD had the same change pattern in the control group and the treatment group. These results suggested that high or low concentrations of ASA could not promote the somatic embryogenesis of and that exogenous ASA had significant effects on the physiology of explants. ASA was also highly related to somatic embryogenesis and the explant browning of Our results could provide a reference for further study on the browning mechanism of explants and lay the foundation for optimizing the condition of somatic embryogenesis in
Topics: Ascorbic Acid; Fraxinus; Glutathione Disulfide; Antioxidants; Superoxide Dismutase; Embryonic Development; Glutathione
PubMed: 36613732
DOI: 10.3390/ijms24010289 -
Journal of Separation Science Jul 2020Ascorbic acid is a powerful antioxidant compound involved in many biological functions, and a chronic deficiency is at the origin of scurvy disease. A simple, rapid, and...
Comprehensive and quantitative stability study of ascorbic acid using capillary zone electrophoresis with ultraviolet detection and high-resolution tandem mass spectrometry.
Ascorbic acid is a powerful antioxidant compound involved in many biological functions, and a chronic deficiency is at the origin of scurvy disease. A simple, rapid, and cost-effective capillary electrophoresis method was developed for the separation and simultaneous quantification of ascorbic acid and the major degradation products: dehydroascorbic acid, furfural, and furoic acid. Systematic optimization of the conditions was performed that enabled baseline separation of the compounds in less than 10 min. In addition to simultaneous quantification of ascorbic acid alongside to the degradation products, stability studies demonstrated the possibility using capillary electrophoresis to separate and identify the major degradation products. Thus, high-resolution tandem mass spectrometry experiments were conducted in order to identify an unknown degradation product separated by capillary electrophoresis and significantly present in degraded samples. Comparison of mass spectrometry data and capillary electrophoresis electropherograms allowed to identify unambiguously trihydroxy-keto-valeraldehyde. Finally, capillary electrophoresis was successfully applied to evaluate the composition of different pharmaceutical preparation of ascorbic acid. Results showed the excellent performance of the capillary electrophoresis method due to the separation of excipients from the compounds of interest, which demonstrated the relevance of using an electrophoretic separation in order to perform comprehensive stability studies of ascorbic acid.
Topics: Ascorbic Acid; Electrophoresis, Capillary; Tandem Mass Spectrometry
PubMed: 32384201
DOI: 10.1002/jssc.202000389 -
International Journal of Molecular... Aug 2020Opioids and their antagonists alter vitamin C metabolism. Morphine binds to glutathione (l-γ-glutamyl-l-cysteinyl-glycine), an intracellular ascorbic acid recycling...
Glutathione and Glutathione-Like Sequences of Opioid and Aminergic Receptors Bind Ascorbic Acid, Adrenergic and Opioid Drugs Mediating Antioxidant Function: Relevance for Anesthesia and Abuse.
Opioids and their antagonists alter vitamin C metabolism. Morphine binds to glutathione (l-γ-glutamyl-l-cysteinyl-glycine), an intracellular ascorbic acid recycling molecule with a wide range of additional activities. The morphine metabolite morphinone reacts with glutathione to form a covalent adduct that is then excreted in urine. Morphine also binds to adrenergic and histaminergic receptors in their extracellular loop regions, enhancing aminergic agonist activity. The first and second extracellular loops of adrenergic and histaminergic receptors are, like glutathione, characterized by the presence of cysteines and/or methionines, and recycle ascorbic acid with similar efficiency. Conversely, adrenergic drugs bind to extracellular loops of opioid receptors, enhancing their activity. These observations suggest functional interactions among opioids and amines, their receptors, and glutathione. We therefore explored the relative binding affinities of ascorbic acid, dehydroascorbic acid, opioid and adrenergic compounds, as well as various control compounds, to glutathione and glutathione-like peptides derived from the extracellular loop regions of the human beta 2-adrenergic, dopamine D1, histamine H1, and mu opioid receptors, as well as controls. Some cysteine-containing peptides derived from these receptors do bind ascorbic acid and/or dehydroascorbic acid and the same peptides generally bind opioid compounds. Glutathione binds not only morphine but also naloxone, methadone, and methionine enkephalin. Some adrenergic drugs also bind to glutathione and glutathione-like receptor regions. These sets of interactions provide a novel basis for understanding some ways that adrenergic, opioid and antioxidant systems interact during anesthesia and drug abuse and may have utility for understanding drug interactions.
Topics: Analgesics, Opioid; Ascorbic Acid; Dehydroascorbic Acid; Enkephalin, Methionine; Glutathione; Humans; Hydromorphone; Methadone; Morphine; Naloxone; Peptides; Receptors, Adrenergic, beta-2; Receptors, Dopamine D1; Receptors, Histamine H1; Receptors, Opioid; Receptors, Opioid, mu
PubMed: 32872204
DOI: 10.3390/ijms21176230