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Journal of Cellular Physiology Dec 2020Oxidative stress and inflammation are crucial factors that increase with age. In the progression of multiple age-related diseases, antioxidants and bioactive compounds...
Oxidative stress and inflammation are crucial factors that increase with age. In the progression of multiple age-related diseases, antioxidants and bioactive compounds have been recognized as useful antiaging agents. Oxidized or reduced vitamin C exerts different actions on tissues and has different metabolism and uptake. In this study, we analyzed the antiaging effect of vitamin C, both oxidized and reduced forms, in renal aging using laser microdissection, quantitative reverse-transcription polymerase chain reaction, and immunohistochemical analyses. In the kidneys of old SAM mice (10 months of age), a model of accelerated senescence, vitamin C, especially in the oxidized form (dehydroascorbic acid [DHA]) improves renal histology and function. Serum creatinine levels and microalbuminuria also decrease after treatment with a decline in azotemia. In addition, sodium-vitamin C cotransporter isoform 1 levels, which were increased during aging, are normalized. In contrast, the pattern of glucose transporter 1 expression is not affected by aging or vitamin C treatment. We conclude that oxidized and reduced vitamin C are potent antiaging therapies and that DHA reverses the kidney damage observed in senescence-accelerated prone mouse 8 to a greater degree.
Topics: Aging; Animals; Ascorbic Acid; Dehydroascorbic Acid; Gene Expression Regulation; Glucose Transporter Type 1; Humans; Inflammation; Kidney; Mice; Oxidative Stress; Sodium-Coupled Vitamin C Transporters
PubMed: 32437012
DOI: 10.1002/jcp.29791 -
Frontiers in Microbiology 2023The production of pyocyanin by increases its virulence, fitness and biofilm formation. Pyocyanin is also a redox molecule and we hypothesize that ascorbic acid being an...
The production of pyocyanin by increases its virulence, fitness and biofilm formation. Pyocyanin is also a redox molecule and we hypothesize that ascorbic acid being an antioxidant will interact with pyocyanin. The main objective of this study was to investigate the potential interaction of ascorbic acid with pyocyanin, and also to investigate the impact of ascorbic acid in combination with Furanone-30 on quorum sensing and biofilm formation of . When incubated with ascorbic acid, hyperchromic and hypsochromic shifts in pyocyanin absorbance peaks at 385 nm and 695 nm were observed. In the presence of dehydroascorbic acid and citric acid, these shifts were absent, indicating that the intrinsic antioxidant property of ascorbic acid was probably essential in binding to pyocyanin. NMR spectroscopy showed shifts in H NMR pyocyanin peaks between 8.2 to 5.8 ppm when incubated in the presence of ascorbic acid. Density Functional Theory (DFT) supported potential interactions between the -CHOH or -OH moieties of ascorbic acid with the -C=O moiety of pyocyanin. The pyocyanin-ascorbic acid complex impaired pyocyanin binding to DNA. Ascorbic acid combined with furanone-30 elevated quorum-sensing inhibition in , which was directly associated with significantly reduced virulence, adhesion, aggregation and biofilm formation and enhanced antibiotic-mediated bacterial killing. This study demonstrated that the antioxidant ascorbic acid directly binds to pyocyanin, modulates its structure and results in disruption of biofilm formation and associated tolerance to antibiotics.
PubMed: 37520362
DOI: 10.3389/fmicb.2023.1166607 -
Redox Biology Jan 2020Under physiological conditions, vitamin C is the main antioxidant found in the central nervous system and is found in two states: reduced as ascorbic acid (AA) and...
Under physiological conditions, vitamin C is the main antioxidant found in the central nervous system and is found in two states: reduced as ascorbic acid (AA) and oxidized as dehydroascorbic acid (DHA). However, under pathophysiological conditions, AA is oxidized to DHA. The oxidation of AA and subsequent production of DHA in neurons are associated with a decrease in GSH concentrations, alterations in glucose metabolism and neuronal death. To date, the endogenous molecules that act as intrinsic regulators of neuronal necroptosis under conditions of oxidative stress are unknown. Here, we show that treatment with AA regulates the expression of pro- and antiapoptotic genes. Vitamin C also regulates the expression of RIPK1/MLKL, whereas the oxidation of AA in neurons induces morphological alterations consistent with necroptosis and MLKL activation. The activation of necroptosis by AA oxidation in neurons results in bubble formation, loss of membrane integrity, and ultimately, cellular explosion. These data suggest that necroptosis is a target for cell death induced by vitamin C.
Topics: Ascorbic Acid; Dehydroascorbic Acid; Necroptosis; Neurons; Oxidation-Reduction; Oxidative Stress
PubMed: 31926631
DOI: 10.1016/j.redox.2019.101408 -
Pharmacological Research Sep 2015Exposure of U937 cells to low concentrations of L-ascorbic acid (AA) is associated with a prompt cellular uptake and a further mitochondrial accumulation of the vitamin....
Exposure of U937 cells to low concentrations of L-ascorbic acid (AA) is associated with a prompt cellular uptake and a further mitochondrial accumulation of the vitamin. Under the same conditions, dehydroascorbic acid (DHA) uptake was followed by rapid reduction and accumulation of identical intracellular levels of AA, however, in the absence of significant mitochondrial uptake. This event was instead observed after exposure to remarkably greater concentrations of DHA. Furthermore, experiments performed in isolated mitochondria revealed that DHA transport through hexose transporters and Na(+) -dependent transport of AA were very similar. These results suggest that the different subcellular compartmentalization of the vitamin is mediated by events promoting inhibition of mitochondrial AA transport, possibly triggered by low levels of DHA. We obtained results in line with this notion in intact cells, and more direct evidence in isolated mitochondria. This inhibitory effect was promptly reversible after DHA removal and comparable with that mediated by established inhibitors, as quercetin. The results presented collectively indicate that low intracellular concentrations of DHA, because of its rapid reduction back to AA, are a poor substrate for direct mitochondrial uptake. DHA concentrations, however, appear sufficiently high to mediate inhibition of mitochondrial transport of AA/DHA-derived AA.
Topics: Ascorbic Acid; Biological Transport; Cell Line, Tumor; Dehydroascorbic Acid; Humans; Mitochondria; Sodium; Sodium-Coupled Vitamin C Transporters; U937 Cells
PubMed: 26188149
DOI: 10.1016/j.phrs.2015.07.004 -
Journal of AOAC International Mar 2021The citrus industry has grown exponentially as a result of increasing demand on its consumption, giving it high standing among other fruit crops. Therefore, the citrus...
The citrus industry has grown exponentially as a result of increasing demand on its consumption, giving it high standing among other fruit crops. Therefore, the citrus sector seeks rapid, easy, and non-destructive approaches to evaluate in real time and in situ the external and internal changes in physical and nutritional quality at any stage of fruit development or storage. In particular, vitamin C is among the most important micronutrients for consumers, but its measurement relies on laborious analytical methodologies. In this study, a portable near infrared spectroscopy (NIRS) sensor was used in combination with chemometrics to develop robust and accurate models to study the ripeness of several citrus fruits (oranges, lemons, clementines, tangerines, and Tahiti limes) and their vitamin C content. Ascorbic acid, dehydroascorbic acid, and total vitamin C were determined by HILIC-HPLC-UV, while soluble solids and total acidity were evaluated by standard analytical procedures. Partial least squares regression (PLSR) was used to build regression models which revealed suitable performance regarding the prediction of quality and ripeness parameters in all tested fruits. Models for ascorbic acid, dehydroascorbic acid, total vitamin C, soluble solids, total acidity, and juiciness showed Rcv2 = 0.77-0.87, Rcv2 = 0.29-0.79, Rcv2 = 0.77-0.86, Rcv2 = 0.75-0.97, Rcv2 = 0.24-0.92, and Rcv2 = 0.38-0.75, respectively. Prediction models of oranges and Tahiti limes showed good to excellent performance regarding all tested conditions. The resulting models confirmed that NIRS technology is a time- and cost-effective approach for predicting citrus fruit quality, which can easily be used by the various stakeholders from the citrus industry.
Topics: Ascorbic Acid; Citrus; Fruit; Least-Squares Analysis; Spectroscopy, Near-Infrared
PubMed: 33351939
DOI: 10.1093/jaoacint/qsaa115 -
Medical Hypotheses Apr 2016In animal models of acute ischemic stroke, intravenous dehydroascorbic acid (DHAA), unlike ascorbic acid (AA), readily enters brain and is converted in both normal and...
In animal models of acute ischemic stroke, intravenous dehydroascorbic acid (DHAA), unlike ascorbic acid (AA), readily enters brain and is converted in both normal and ischemic brain into protective ascorbic acid. When given parenterally DHAA minimizes infarct volume and facilitates functional recovery. I hypothesize the same effect will occur in humans with acute ischemic stroke. Efficacy in reducing infarct volume is demonstrable in mice and rats even when DHAA is infused three hours after the experimental infarct. Moreover, there is fivefold mechanistic rational for DHA beside excellent pharmacokinetics and rapid penetration of brain and conversion to protective AA: (1) in ischemic brain, there is a precipitous decline in AA which can be reversed by intravenous DHAA; (2) after reduction of DHAA to AA in both normal and ischemic brain, AA can reduce oxidized vitamin E and glutathione, other protectors of brain against damaging reactive oxygen species which build up in ischemic brain; (3) AA itself can protect brain against damaging reactive oxygen species; (4) AA is an essential cofactor for several enzymes in brain including ten-eleven translocase-2 which upregulates production of protective molecules like brain-derived neurotrophic factor; and (5) DHAA after conversion to AA prevents both lipid oxidation and presumably oxidation of other labile substances (e.g., dopamine) in ischemic brain. In terms of safety, based on all available animal information, DHAA is safe in the proposed dosing regimen. For human clinical trials, the methodology for conducting the proposed animal safety, clinical pharmacology and phase II efficacy studies is straightforward. Finally, if DHAA preserved brain substance and function in humans, it could be employed in pre-hospital stroke patients.
Topics: Animals; Ascorbic Acid; Brain; Dehydroascorbic Acid; Evidence-Based Medicine; Humans; Models, Neurological; Stroke; Treatment Outcome; Vitamins
PubMed: 26968905
DOI: 10.1016/j.mehy.2016.01.021 -
Archives of Biochemistry and Biophysics Jul 2019Recent development in electronics has enabled the use of non-thermal plasma (NTP) to strictly direct oxidative stress in a defined location at near-physiological...
Recent development in electronics has enabled the use of non-thermal plasma (NTP) to strictly direct oxidative stress in a defined location at near-physiological temperature. In preclinical studies or human clinical trials, NTP promotes blood coagulation, wound healing with disinfection, and selective killing of cancer cells. Although these biological effects of NTP have been widely explored, the stoichiometric quantitation of free radicals in liquid phase has not been performed in the presence of biocompatible reducing agents, which may modify the final biological effects of NTP. Here we quantitated hydroxyl radicals, a major reactive oxygen species generated after NTP exposure, by electron paramagnetic resonance (EPR) spectroscopy using two distinct spin-trapping probes, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (M4PO), in the presence of thiols or antioxidants. l-Ascorbic acid (AsA) at 25-50 μM concentrations (physiological concentration in the serum) significantly scavenged these hydroxyl radicals, whereas dithiothreitol (DTT), reduced glutathione (GSH), and N-acetyl-cysteine (NAC) as thiols were required in millimolar concentrations to perform scavenging activities. l-Dehydroascorbic acid (DHA), an oxidized form of AsA, necessitated the presence of 25-50 μM DTT or sub-millimolar concentrations of GSH and NAC for the scavenging of hydroxyl radicals and failed to scavenge hydroxyl radicals by itself. These results suggest that the redox cycling of AsA/DHA via thiols and cellular AsA metabolism are important processes to be considered while applying NTP to cells and tissues. Further studies are warranted to elucidate the interaction between other reactive species generated by NTP and biomolecules to promote biological and medical applications of NTP.
Topics: Acetylcysteine; Ascorbic Acid; Cyclic N-Oxides; Dehydroascorbic Acid; Dithiothreitol; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Glutathione; Hydroxyl Radical; Plasma Gases; Spin Labels
PubMed: 31153952
DOI: 10.1016/j.abb.2019.05.019 -
Archives of Biochemistry and Biophysics Mar 2021Non-thermal plasma (NTP) devices generate reactive oxygen species (ROS) and reactive nitrogen species, such as singlet oxygen (O), superoxide (O), hydroxyl radical (OH),...
Non-thermal plasma (NTP) devices generate reactive oxygen species (ROS) and reactive nitrogen species, such as singlet oxygen (O), superoxide (O), hydroxyl radical (OH), hydrogen peroxide (HO), ozone, and nitric oxide at near-physiological temperature. In preclinical studies, NTP promotes blood coagulation, wound healing with disinfection, and selective killing of cancer cells. Although these biological effects of NTP have been widely explored, the stoichiometric quantitation of ROS in the liquid phase has not been performed in the presence of biocompatible reducing agents, which may modify the final biological effects of NTP. Here, we utilized electron paramagnetic resonance spectroscopy to quantitate OH, using a spin-trapping probe 5,5-dimethyl-1-pyrroline-N-oxide; O, using a fluorescent probe; and O and HO, using luminescent probes, after NTP exposure in the presence of antioxidants. l-ascorbate (Asc) at 50 μM concentration (physiological concentration in serum) significantly scavenged OH, whereas (-)-epigallocatechin gallate (EGCG) and α-tocopherol were also effective at performing scavenging activities at 250 μM concentrations. Asc significantly scavenged O and HO at 100 μM. l-Dehydroascorbate (DHA), an oxidized form of Asc, degraded HO, whereas it did not quench OH or O, which are sources of HO. Furthermore, EGCG efficiently scavenged NTP-induced O, O, and HO in Chelex-treated water. These results indicate that the redox cycling of Asc/DHA and metabolites of DHA are important to be considered when applying NTP to cells and tissues. Additionally, ROS-reducing compounds, such as EGCG, affect the outcome. Further studies are warranted to elucidate the interaction between ROS and biomolecules to promote the medical applications of NTP.
Topics: Dehydroascorbic Acid; Hydrogen Peroxide; Oxidation-Reduction; Plasma Gases
PubMed: 33482147
DOI: 10.1016/j.abb.2021.108762 -
Spectrochimica Acta. Part A, Molecular... Nov 2022Ascorbate oxidase (AAO) and ascorbic acid (AA) play an important role in delaying lives senescence and metabolism. In this study, a sensitive ratiometric fluorescence...
Modulation of inner filter effect between persistent luminescent particles and 2, 3-diaminophenazine for ratiometric fluorescent assay of ascorbic acid and ascorbate oxidase activity.
Ascorbate oxidase (AAO) and ascorbic acid (AA) play an important role in delaying lives senescence and metabolism. In this study, a sensitive ratiometric fluorescence sensing system based on the inner filter effect (IFE) between persistent luminescent particles (PLPs) and 2, 3-diaminophenazine (DAP), was designed for the detection of AA and AAO activity. Wherein, PLPs emit blue fluorescence at 475 nm with an excitation wavelength of 370 nm. CoOOH nanosheets with oxidase-like activity can oxidize o-phenylenediamine (OPD) to produce 2, 3-diaminophenazine (DAP) with orange fluorescence at 558 nm. The generated DAP quenched the fluorescence of PLPs by an inner filter effect (IFE). When AA was introduced to the system, CoOOH nanosheets were destroyed and reduced to Co, thereby inhibiting the oxidization of OPD and effectively preserving the blue fluorescence of PLPs at 475 nm. Besides, AAO can catalyse AA to produce the oxided dehydroascorbic acid (DHA). The dissipative AA can recover orange fluorescence of DAP with weakening the blue fluorescence of PLPs. Therefore, a sensitive ratio fluorescence sensing strategy was established by using PLPs as the reference signal and DAP as a reported signal for the detection of AA and AAO activity. Under optimal conditions, the obtained linear ranges were 1-45 μM and 1-20 mU/mL, and detection limits were 0.2 μM and 0.25 mU/mL, respectively. Finally, this proposed ratiometric fluorescent analytical strategy was used to detect AA in real samples (lemon, orange, tomato), which exhibited satisfactory results comparing with commercial kit.
Topics: Ascorbate Oxidase; Ascorbic Acid; Coloring Agents; Limit of Detection; Spectrometry, Fluorescence
PubMed: 35797885
DOI: 10.1016/j.saa.2022.121564 -
Acta Pharmaceutica Sinica. B Jul 2019Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation,...
Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them. The purpose of this work is to construct a self-assembled glutathione (GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription (RCT) method. GSH-responsive cationic polymer polyethyleneimine (pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid (DHA), a targeting molecule, which is a substrate of glucose transporter 1 (GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.
PubMed: 31384542
DOI: 10.1016/j.apsb.2019.01.012