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Antioxidants, Volume 10, Issue 3 (March 2021) – 166 articles

Cover Story (view full-size image): In the current study, we investigated exercise-induced atrial alterations using a small animal model, where balanced swim training protocol resulted in left ventricular physiological hypertrophy and functional improvement. A detailed investigation of atrial function and structure showed physiological myocardial hypertrophy with increased capillary density, lack of pathological processes, such as profibrotic and inflammatory response, and a balance between oxidative stress and antioxidant mechanisms. A decreased expression of potassium channels and connexin-43 might contribute to prolonged atrial effective refractory period. The lack of arrhythmia inducibility suggests benign electrical remodeling. Our results point out that a balanced intense training program—without excessive exercise episodes or usage of performance-enhancing drugs—is associated with benign, physiological atrial [...] Read more.
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Article
Comprehensive Phenolic and Free Amino Acid Analysis of Rosemary Infusions: Influence on the Antioxidant Potential
Antioxidants 2021, 10(3), 500; https://doi.org/10.3390/antiox10030500 - 23 Mar 2021
Cited by 4 | Viewed by 1166
Abstract
The phenolics profile, free amino acids composition, and antioxidant potential of rosemary infusions were studied. Forty-four compounds belonging to nine different groups (hydroxybenzoic acids, hydroxycinnamic acids, flavan-3-ols, flavanones, flavones, phenolic diterpenes, hydroxybenzaldehydes, coumarins, and pyranochromanones) were identified by UHPLC-ESI-Q-TOF-MS. Of these, seven were [...] Read more.
The phenolics profile, free amino acids composition, and antioxidant potential of rosemary infusions were studied. Forty-four compounds belonging to nine different groups (hydroxybenzoic acids, hydroxycinnamic acids, flavan-3-ols, flavanones, flavones, phenolic diterpenes, hydroxybenzaldehydes, coumarins, and pyranochromanones) were identified by UHPLC-ESI-Q-TOF-MS. Of these, seven were firstly described in rosemary infusions: a rosmanol derivative, two dihydroxycoumarin hexosides, a hydroxybenzaldehyde, a dihydroxybenzoic acid hexoside, coumaric acid hexoside, and isocalolongic acid. The free amino acid profile of the beverages was also reported by the first time with seven amino acids found (asparagine, threonine, alanine, tyrosine, phenylalanine, isoleucine, and proline). Furthermore, DPPH scavenging ability, Ferric Reducing Antioxidant Power and Oxygen Radical Absorbance Capacity, as well as total phenolics and flavonoids contents, were assessed. Overall, rosemary infusions showed to be a very good source of antioxidants. A 200 mL cup of this infusion contributes to the ingestion of ~30 mg of phenolic compounds and about 0.5–1.1 μg of free amino acids. This type of beverages may present a positive impact on the maintenance of the body antioxidant status and contribute to the prevention of oxidative stress related diseases. Full article
(This article belongs to the Special Issue Dietary Antioxidants in Mediterranean Diet)
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Review
Stoichiometric Thiol Redox Proteomics for Quantifying Cellular Responses to Perturbations
Antioxidants 2021, 10(3), 499; https://doi.org/10.3390/antiox10030499 - 23 Mar 2021
Cited by 7 | Viewed by 1427
Abstract
Post-translational modifications regulate the structure and function of proteins that can result in changes to the activity of different pathways. These include modifications altering the redox state of thiol groups on protein cysteine residues, which are sensitive to oxidative environments. While mass spectrometry [...] Read more.
Post-translational modifications regulate the structure and function of proteins that can result in changes to the activity of different pathways. These include modifications altering the redox state of thiol groups on protein cysteine residues, which are sensitive to oxidative environments. While mass spectrometry has advanced the identification of protein thiol modifications and expanded our knowledge of redox-sensitive pathways, the quantitative aspect of this technique is critical for the field of redox proteomics. In this review, we describe how mass spectrometry-based redox proteomics has enabled researchers to accurately quantify the stoichiometry of reversible oxidative modifications on specific cysteine residues of proteins. We will describe advancements in the methodology that allow for the absolute quantitation of thiol modifications, as well as recent reports that have implemented this approach. We will also highlight the significance and application of such measurements and why they are informative for the field of redox biology. Full article
(This article belongs to the Special Issue Modifications of Cysteine Proteins Redox Status in Cell Signalling)
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Article
Characterization of NADPH Oxidase Expression and Activity in Acute Myeloid Leukemia Cell Lines: A Correlation with the Differentiation Status
Antioxidants 2021, 10(3), 498; https://doi.org/10.3390/antiox10030498 - 23 Mar 2021
Cited by 4 | Viewed by 1062
Abstract
In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the [...] Read more.
In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the oxidants, NADPH oxidases (NOX) generate ROS as a physiological function. Although it has been reported in AML initiation and development, the contribution of NOX to the ROS production in AML remains to be clarified. The aim of this study was to investigate the NOX expression and function in AML, and to examine the role of NOX in blast proliferation and differentiation. First, we interrogated the NOX expression in primary cells from public datasets, and investigated their association with prognostic markers. Next, we explored the NOX expression and activity in AML cell lines, and studied the impact of NOX knockdown on cell proliferation and differentiation. We found that NOX2 is ubiquitously expressed in AML blasts, and particularly in cells from the myelomonocytic (M4) and monocytic (M5) stages; however, it is less expressed in LSCs and in relapsed AML. This is consistent with an increased expression throughout normal hematopoietic differentiation, and is reflected in AML cell lines. Nevertheless, no endogenous NOX activity could be detected in the absence of PMA stimulation. Furthermore, CYBB knockdown, although hampering induced NOX2 activity, did not affect the proliferation and differentiation of THP-1 and HL-60 cells. In summary, our data suggest that NOX2 is a marker of AML blast differentiation, while AML cell lines lack any NOX2 endogenous activity. Full article
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Article
Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors
Antioxidants 2021, 10(3), 497; https://doi.org/10.3390/antiox10030497 - 23 Mar 2021
Cited by 4 | Viewed by 1152
Abstract
Background: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors. Objectives: To establish whether PDI and [...] Read more.
Background: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors. Objectives: To establish whether PDI and Nox-1 cooperate to control platelet function. Methods: Immunofluorescence microscopy was utilised to determine expression and localisation of PDI and Nox-1. Platelet aggregation, fibrinogen binding, P-selectin exposure, spreading and calcium mobilization were measured as markers of platelet function. A cross-sectional population study (n = 136) was conducted to assess the relationship between platelet PDI and Nox-1 levels and cardiometabolic risk factors. Results: PDI and Nox-1 co-localized upon activation induced by the collagen receptor GPVI. Co-inhibition of PDI and Nox-1 led to additive inhibition of GPVI-mediated platelet aggregation, activation and calcium flux. This was confirmed in murine Nox-1−/− platelets treated with PDI inhibitor bepristat, without affecting bleeding. PDI and Nox-1 together contributed to GPVI signalling that involved the phosphorylation of p38 MAPK, p47phox, PKC and Akt. Platelet PDI and Nox-1 levels were upregulated in obesity, with platelet Nox-1 also elevated in hypertensive individuals. Conclusions: We show that PDI and Nox-1 cooperate to control platelet function and are associated with cardiometabolic risk factors. Full article
(This article belongs to the Special Issue Redox-Dependent Regulation of Haemostasis in Health and Disease)
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Article
Cyclooxygenase-2 Glycosylation Is Affected by Peroxynitrite in Endothelial Cells: Impact on Enzyme Activity and Degradation
Antioxidants 2021, 10(3), 496; https://doi.org/10.3390/antiox10030496 - 23 Mar 2021
Cited by 2 | Viewed by 872
Abstract
The exposure of human endothelial cells to 3-morpholinosydnonimine (SIN-1) induced the expression of cyclooxygenase-2 (COX-2) in a dose- and time-dependent manner. Interestingly, after a prolonged incubation (>8 h) several proteoforms were visualized by Western blot, corresponding to different states of glycosylation of the [...] Read more.
The exposure of human endothelial cells to 3-morpholinosydnonimine (SIN-1) induced the expression of cyclooxygenase-2 (COX-2) in a dose- and time-dependent manner. Interestingly, after a prolonged incubation (>8 h) several proteoforms were visualized by Western blot, corresponding to different states of glycosylation of the protein. This effect was specific for SIN-1 that generates peroxynitrite and it was not detected with other nitric oxide-donors. Metabolic labeling experiments using 35S or cycloheximide suggested that the formation of hypoglycosylated COX-2 was dependent on de novo synthesis of the protein rather than the deglycosylation of the native protein. Moreover, SIN-1 reduced the activity of the hexokinase, the enzyme responsible for the first step of glycolysis. The hypoglycosylated COX-2 induced by SIN-1 showed a reduced capacity to generate prostaglandins and the activity was only partially recovered after immunoprecipitation. Finally, hypoglycosylated COX-2 showed a more rapid rate of degradation compared to COX-2 induced by IL-1α and an alteration in the localization with an accumulation mainly detected in the nuclear membrane. Our results have important implication to understand the effect of peroxynitrite on COX-2 expression and activity, and they may help to identify new pharmacological tools direct to increase COX-2 degradation or to inhibit its activity. Full article
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Article
The Nutraceutical Properties of “Pizza Napoletana Marinara TSG” a Traditional Food Rich in Bioaccessible Antioxidants
Antioxidants 2021, 10(3), 495; https://doi.org/10.3390/antiox10030495 - 22 Mar 2021
Cited by 5 | Viewed by 1910
Abstract
Italian gastronomy experiences have ever-enhancing fame around the world. It is due to the linkage between taste and salubriousness commonly related to Mediterranean foods. The market proposes many types of pizza to suit all palates. The antioxidant potential of the “Pizza Napoletana marinara” [...] Read more.
Italian gastronomy experiences have ever-enhancing fame around the world. It is due to the linkage between taste and salubriousness commonly related to Mediterranean foods. The market proposes many types of pizza to suit all palates. The antioxidant potential of the “Pizza Napoletana marinara” included in the register of traditional specialties guaranteed (TSG) was determined in this work. ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) method evaluated the antioxidant activity of the pizza homogenized. In vitro digestion models estimated the intestinal and gastric bioaccessibility of the main antioxidant compounds (lycopene and phenolics). To our knowledge, this is the first study to provide the content, antioxidant potential, and bioaccessibility of the antioxidants (polyphenols and lycopene) contained in the traditional pizza “marinara TSG”. Our results showed that the “Pizza Napoletana marinara” had polyphenols concentration, lycopene level, antioxidant activity, and bioaccessibility of phenolic compounds and lycopene better than other similar pizzas. They confirmed the nutritional importance of traditional preparations and established the nutraceutical potential of “pizza marinara TSG” as a food rich in bio-accessible antioxidants. Full article
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Article
Aesculetin Inhibits Airway Thickening and Mucus Overproduction Induced by Urban Particulate Matter through Blocking Inflammation and Oxidative Stress Involving TLR4 and EGFR
Antioxidants 2021, 10(3), 494; https://doi.org/10.3390/antiox10030494 - 22 Mar 2021
Cited by 4 | Viewed by 1128
Abstract
Particulate matter (PM) is a mixture of solid and liquid air pollutant particles suspended in the air, varying in composition, size, and physical features. PM is the most harmful form of air pollution due to its ability to penetrate deep into the lungs [...] Read more.
Particulate matter (PM) is a mixture of solid and liquid air pollutant particles suspended in the air, varying in composition, size, and physical features. PM is the most harmful form of air pollution due to its ability to penetrate deep into the lungs and blood streams, causing diverse respiratory diseases. Aesculetin, a coumarin derivative present in the Sancho tree and chicory, is known to have antioxidant and anti-inflammatory effects in the vascular and immune system. However, its effect on PM-induced airway thickening and mucus hypersecretion is poorly understood. The current study examined whether naturally-occurring aesculetin inhibited airway thickening and mucus hypersecretion caused by urban PM10 (uPM10, particles less than 10 μm). Mice were orally administrated with 10 mg/kg aesculetin and exposed to 6 μg/mL uPM10 for 8 weeks. To further explore the mechanism(s) involved in inhibition of uPM10-induced mucus hypersecretion by aesculetin, bronchial epithelial BEAS-2B cells were treated with 1–20 µM aesculetin in the presence of 2 μg/mL uPM10. Oral administration of aesculetin attenuated collagen accumulation and mucus hypersecretion in the small airways inflamed by uPM10. In addition, aesculetin inhibited uPM10-evoked inflammation and oxidant production in lung tissues. Further, aesculetin accompanied the inhibition of induction of bronchial epithelial toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EFGR) elevated by uPM10. The inhibition of TLR4 and EGFR accompanied bronchial mucus hypersecretion in the presence of uPM10. Oxidative stress was responsible for the epithelial induction of TLR4 and EGFR, which was disrupted by aesculetin. These results demonstrated that aesculetin ameliorated airway thickening and mucus hypersecretion by uPM10 inhalation by inhibiting pulmonary inflammation via oxidative stress-stimulated TLR4 and EGFR. Therefore, aesculetin may be a promising agent for treating airway mucosa-associated disorders elicited by urban coarse particulates. Full article
(This article belongs to the Special Issue Antioxidants and Lung Diseases)
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Article
The Impact of Early Pregnancy and Exposure to Tobacco Smoke on Blood Antioxidant Status and Copper, Zinc, Cadmium Concentration—A Pilot Study
Antioxidants 2021, 10(3), 493; https://doi.org/10.3390/antiox10030493 - 22 Mar 2021
Cited by 3 | Viewed by 862
Abstract
The aim of the study was to evaluate the impact of early pregnancy and exposure to tobacco smoke on antioxidant status and copper, zinc, and cadmium concentrations in the blood of non-smoking and smoking, as well as non-pregnant or pregnant women. The study [...] Read more.
The aim of the study was to evaluate the impact of early pregnancy and exposure to tobacco smoke on antioxidant status and copper, zinc, and cadmium concentrations in the blood of non-smoking and smoking, as well as non-pregnant or pregnant women. The study included 213 women. More specifically, 150 women in first trimester of pregnancy and 63 non-pregnant women. Women were divided into subgroups according to exposure to tobacco smoke. Pregnancy significant influences higher copper and lower zinc concentration in the serum, whereas exposure to tobacco smoke during pregnancy is mainly associated with an elevation in cadmium and zinc concentration. It seems that metallothionein, superoxide dismutase, and glutathione peroxidase are the important antioxidants during early pregnancy, when exposure to tobacco smoke occurs, whereas the pregnancy itself is associated with a higher concentration of metallothionein and activity of catalase. Both pregnancy in the first trimester and exposure to tobacco smoke decrease glutathione concentration. In addition, active and passive maternal smoking have a similarly negative effect on antioxidant status in the first trimester. Early pregnancy as well as exposure to tobacco smoke is associated with significant alteration in antioxidant status and copper, zinc, and cadmium concentration. Due to a small number of smoking subjects (11 cases of non-pregnant, active smokers and 14 pregnant active smokers), the obtained results should be treated as a pilot, and this should be considered for future studies. Full article
(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development)
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Review
Pterostilbene in Cancer Therapy
Antioxidants 2021, 10(3), 492; https://doi.org/10.3390/antiox10030492 - 21 Mar 2021
Cited by 11 | Viewed by 1472
Abstract
Natural polyphenols are organic chemicals which contain phenol units in their structures and possess antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene; PT) is a phytoalexin originally isolated from the heartwood of [...] Read more.
Natural polyphenols are organic chemicals which contain phenol units in their structures and possess antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene; PT) is a phytoalexin originally isolated from the heartwood of red sandalwood. As recently reported by our group, PT was shown to be effective in the treatment of melanoma. Counterintuitively, PT is not effective (cytotoxic) against melanoma in vitro, and only under in vivo conditions does PT display its anticancer activity. This study elucidated that PT can be effective against melanoma through the inhibition of adrenocorticotropic hormone production in the brain of a mouse, which weakens the Nrf2-dependent antioxidant defenses of melanoma and also pancreatic cancers. This results in both the inhibition of tumor growth and sensitization of the tumor to oxidative stress. Moreover, PT can promote cancer cell death via a mechanism involving lysosomal membrane permeabilization. Different grades of susceptibility were observed among the different cancer cells depending on their lysosomal heat shock protein 70 content, a known stabilizer of lysosomal membranes. In addition, the safety of PT administered i.v. has been evaluated in mice. PT was found to be pharmacologically safe because it showed no organ-specific or systemic toxicity (including tissue histopathologic examination and regular hematology and clinical chemistry data) even when administered i.v. at a high dose (30 mg/kg per day × 23 days). Moreover, new pharmacological advances are being developed to increase its bioavailability and, thereby, its bioefficacy. Therefore, although applications of PT in cancer therapy are just beginning to be explored, it represents a potential (and effective) adjuvant/sensitizing therapy which may improve the results of various oncotherapies. The aim of this review is to present and discuss the results that in our opinion best support the usefulness of PT in cancer therapy, making special emphasis on the in vivo evidence. Full article
(This article belongs to the Special Issue Antioxidants and Cancer)
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Review
Implication of Dietary Iron-Chelating Bioactive Compounds in Molecular Mechanisms of Oxidative Stress-Induced Cell Ageing
Antioxidants 2021, 10(3), 491; https://doi.org/10.3390/antiox10030491 - 21 Mar 2021
Cited by 3 | Viewed by 1197
Abstract
One of the prevailing perceptions regarding the ageing of cells and organisms is the intracellular gradual accumulation of oxidatively damaged macromolecules, leading to the decline of cell and organ function (free radical theory of ageing). This chemically undefined material known as “lipofuscin,” “ceroid,” [...] Read more.
One of the prevailing perceptions regarding the ageing of cells and organisms is the intracellular gradual accumulation of oxidatively damaged macromolecules, leading to the decline of cell and organ function (free radical theory of ageing). This chemically undefined material known as “lipofuscin,” “ceroid,” or “age pigment” is mainly formed through unregulated and nonspecific oxidative modifications of cellular macromolecules that are induced by highly reactive free radicals. A necessary precondition for reactive free radical generation and lipofuscin formation is the intracellular availability of ferrous iron (Fe2+) (“labile iron”), catalyzing the conversion of weak oxidants such as peroxides, to extremely reactive ones like hydroxyl (HO) or alcoxyl (RO) radicals. If the oxidized materials remain unrepaired for extended periods of time, they can be further oxidized to generate ultimate over-oxidized products that are unable to be repaired, degraded, or exocytosed by the relevant cellular systems. Additionally, over-oxidized materials might inactivate cellular protection and repair mechanisms, thus allowing for futile cycles of increasingly rapid lipofuscin accumulation. In this review paper, we present evidence that the modulation of the labile iron pool distribution by nutritional or pharmacological means represents a hitherto unappreciated target for hampering lipofuscin accumulation and cellular ageing. Full article
(This article belongs to the Special Issue Dietary Antioxidants in Mediterranean Diet)
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Article
Development of Water-Insoluble Vehicle Comprising Natural Cyclodextrin—Vitamin E Complex
Antioxidants 2021, 10(3), 490; https://doi.org/10.3390/antiox10030490 - 20 Mar 2021
Cited by 2 | Viewed by 1036
Abstract
Development of a novel antioxidant-delivery vehicle exerting biosafety has been attracting a great deal of interest. In this study, a vehicle comprising a natural composite consisting of vitamin E (α-tocopherol; Toc) and cyclodextrin (CD) additives was developed, directed toward aqua-related biological applications. Not [...] Read more.
Development of a novel antioxidant-delivery vehicle exerting biosafety has been attracting a great deal of interest. In this study, a vehicle comprising a natural composite consisting of vitamin E (α-tocopherol; Toc) and cyclodextrin (CD) additives was developed, directed toward aqua-related biological applications. Not only β-CD, but also γ-CD, tended to form a water-insoluble aggregate with Toc in aqueous media. The aggregated vehicle, in particular the γ-CD-added system, showed a remarkable sustained effect because of slow dynamics. Furthermore, a prominent cytoprotective effect by the γ-CD–Toc vehicle under the oxidative stress condition was confirmed. Thus, the novel vitamin E vehicle motif using γ-CD as a stabilizer was proposed, widening the usability of Toc for biological applications. Full article
(This article belongs to the Collection Advances in Antioxidant Ingredients from Natural Products)
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Article
NAC and Vitamin D Restore CNS Glutathione in Endotoxin-Sensitized Neonatal Hypoxic-Ischemic Rats
Antioxidants 2021, 10(3), 489; https://doi.org/10.3390/antiox10030489 - 20 Mar 2021
Cited by 3 | Viewed by 1143
Abstract
Therapeutic hypothermia does not improve outcomes in neonatal hypoxia ischemia (HI) complicated by perinatal infection, due to well-described, pre-existing oxidative stress and neuroinflammation that shorten the therapeutic window. For effective neuroprotection post-injury, we must first define and then target CNS metabolomic changes immediately [...] Read more.
Therapeutic hypothermia does not improve outcomes in neonatal hypoxia ischemia (HI) complicated by perinatal infection, due to well-described, pre-existing oxidative stress and neuroinflammation that shorten the therapeutic window. For effective neuroprotection post-injury, we must first define and then target CNS metabolomic changes immediately after endotoxin-sensitized HI (LPS-HI). We hypothesized that LPS-HI would acutely deplete reduced glutathione (GSH), indicating overwhelming oxidative stress in spite of hypothermia treatment in neonatal rats. Post-natal day 7 rats were randomized to sham ligation, or severe LPS-HI (0.5 mg/kg 4 h before right carotid artery ligation, 90 min 8% O2), followed by hypothermia alone or with N-acetylcysteine (25 mg/kg) and vitamin D (1,25(OH)2D3, 0.05 μg/kg) (NVD). We quantified in vivo CNS metabolites by serial 7T MR Spectroscopy before, immediately after LPS-HI, and after treatment, along with terminal plasma drug concentrations. GSH was significantly decreased in all LPS-HI rats compared with baseline and sham controls. Two hours of hypothermia alone did not improve GSH and allowed glutamate + glutamine (GLX) to increase. Within 1 h of administration, NVD increased GSH close to baseline and suppressed GLX. The combination of NVD with hypothermia rapidly improved cellular redox status after LPS-HI, potentially inhibiting important secondary injury cascades and allowing more time for hypothermic neuroprotection. Full article
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Article
To Synthesize Hydroxyapatite by Modified Low Temperature Method Loaded with Bletilla striata Polysaccharide as Antioxidant for the Prevention of Sarcopenia by Intramuscular Administration
Antioxidants 2021, 10(3), 488; https://doi.org/10.3390/antiox10030488 - 20 Mar 2021
Cited by 4 | Viewed by 1061
Abstract
Oxidative stress has been suggested as an important factor in the progress of sarcopenia. The current treatments for sarcopenia have the disadvantages of insufficient effect or daily administration. Therefore, an alternative for effective, safety and long-term treatment may be a solution for unmet [...] Read more.
Oxidative stress has been suggested as an important factor in the progress of sarcopenia. The current treatments for sarcopenia have the disadvantages of insufficient effect or daily administration. Therefore, an alternative for effective, safety and long-term treatment may be a solution for unmet needs. Bletilla striata polysaccharide has been reported to have anti­oxidative and anti-inflammatory properties. In this study, we used Bletilla striata polysaccharide (BSP) combined with hydroxyapatite, a carrier. We hypothesized that the resulting combination (BSP-HAP) is a good formula for the controlled release of BSP via intramuscular (IM) administration, so as to prevent the worsening of presarcopenia or even recover from the early stage of the illness. In this research, BSP-HAP was synthesized by a modified low temperature co-precipitation process that would be beneficial for BSP loading. By conducting DCFDA, WST-1 and the Live/Dead assay, BSP-HAP is shown to be a biocompatible material which may release BSP by cells through the endocytosis pathway. Animal studies revealed that the rats treated with BSP-HAP could effectively recover muscle endurance, grip strength or fat/lean mass ratio from lipopolysaccharide (LPS)-induced sarcopenia. This study shows BSP delivered by BSP-HAP system has potential for application in the treatment and prevention of sarcopenia in the future. Full article
(This article belongs to the Special Issue Oxidative Stress in Skeletal Muscle)
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Article
Fructose Removal from the Diet Reverses Inflammation, Mitochondrial Dysfunction, and Oxidative Stress in Hippocampus
Antioxidants 2021, 10(3), 487; https://doi.org/10.3390/antiox10030487 - 20 Mar 2021
Cited by 3 | Viewed by 1560
Abstract
Young age is often characterized by high consumption of processed foods and fruit juices rich in fructose, which, besides inducing a tendency to become overweight, can promote alterations in brain function. The aim of this study was therefore to (a) clarify brain effects [...] Read more.
Young age is often characterized by high consumption of processed foods and fruit juices rich in fructose, which, besides inducing a tendency to become overweight, can promote alterations in brain function. The aim of this study was therefore to (a) clarify brain effects resulting from fructose consumption in juvenile age, a critical phase for brain development, and (b) verify whether these alterations can be rescued after removing fructose from the diet. Young rats were fed a fructose-rich or control diet for 3 weeks. Fructose-fed rats were then fed a control diet for a further 3 weeks. We evaluated mitochondrial bioenergetics by high-resolution respirometry in the hippocampus, a brain area that is critically involved in learning and memory. Glucose transporter-5, fructose and uric acid levels, oxidative status, and inflammatory and synaptic markers were investigated by Western blotting and spectrophotometric or enzyme-linked immunosorbent assays. A short-term fructose-rich diet induced mitochondrial dysfunction and oxidative stress, associated with an increased concentration of inflammatory markers and decreased Neurofilament-M and post-synaptic density protein 95. These alterations, except for increases in haptoglobin and nitrotyrosine, were recovered by returning to a control diet. Overall, our results point to the dangerous effects of excessive consumption of fructose in young age but also highlight the effect of partial recovery by switching back to a control diet. Full article
(This article belongs to the Special Issue Oxidative Stress, Neuroinflammation and Neurodegeneration)
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Review
Endothelium as a Source and Target of H2S to Improve Its Trophism and Function
Antioxidants 2021, 10(3), 486; https://doi.org/10.3390/antiox10030486 - 19 Mar 2021
Cited by 9 | Viewed by 1272
Abstract
The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood [...] Read more.
The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood flow homeostasis and fulfill tissue metabolic demands by furnishing oxygen and nutrients. The endothelium regulates the proper functioning of vessels and microcirculation, in terms of tone control, blood fluidity, and fine tuning of inflammatory and redox reactions within the vessel wall and in surrounding tissues. This multiplicity of effects is due to the ability of ECs to produce, process, and release key modulators. Among these, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H2S) are very active molecules constitutively produced by endotheliocytes for the maintenance and control of vascular physiological functions, while their impairment is responsible for endothelial dysfunction and cardiovascular disorders such as hypertension, atherosclerosis, and impaired wound healing and vascularization due to diabetes, infections, and ischemia. Upregulation of H2S producing enzymes and administration of H2S donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease progression. This review will focus on the beneficial autocrine/paracrine properties of H2S on ECs and the state of the art on H2S potentiating drugs and tools. Full article
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Review
Hydrogen Sulfide as a Potential Therapy for Heart Failure—Past, Present, and Future
Antioxidants 2021, 10(3), 485; https://doi.org/10.3390/antiox10030485 - 19 Mar 2021
Cited by 5 | Viewed by 997
Abstract
Hydrogen sulfide (H2S) is an endogenous, gaseous signaling molecule that plays a critical role in cardiac and vascular biology. H2S regulates vascular tone and oxidant defenses and exerts cytoprotective effects in the heart and circulation. Recent studies indicate that [...] Read more.
Hydrogen sulfide (H2S) is an endogenous, gaseous signaling molecule that plays a critical role in cardiac and vascular biology. H2S regulates vascular tone and oxidant defenses and exerts cytoprotective effects in the heart and circulation. Recent studies indicate that H2S modulates various components of metabolic syndrome, including obesity and glucose metabolism. This review will discuss studies exhibiting H2S -derived cardioprotective signaling in heart failure with reduced ejection fraction (HFrEF). We will also discuss the role of H2S in metabolic syndrome and heart failure with preserved ejection fraction (HFpEF). Full article
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Editorial
Lipid Peroxidation in Neurodegeneration
Antioxidants 2021, 10(3), 484; https://doi.org/10.3390/antiox10030484 - 19 Mar 2021
Cited by 2 | Viewed by 666
Abstract
Neurodegenerative diseases have multiple social and economic impacts on society, and they are the cause of millions of deaths every year [...] Full article
(This article belongs to the Special Issue Lipid Peroxidation in Neurodegeneration)
Article
CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis
Antioxidants 2021, 10(3), 483; https://doi.org/10.3390/antiox10030483 - 19 Mar 2021
Cited by 4 | Viewed by 1305
Abstract
Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed [...] Read more.
Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy. Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years (p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L (p < 0.01). Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF. Full article
(This article belongs to the Special Issue Commemorative Issue of Antioxidants Dedicated to Peter Eckl)
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Perspective
Potentials of Raspberry Ketone as a Natural Antioxidant
Antioxidants 2021, 10(3), 482; https://doi.org/10.3390/antiox10030482 - 18 Mar 2021
Cited by 2 | Viewed by 1451
Abstract
Oxidative stress is closely linked to various diseases, and many studies have been conducted to determine how to reduce this stress. In particular, efforts are being made to find potential antioxidants from natural products. Studies have shown that raspberry ketone (RK; 4-(4-hydroxyphenyl)-2-butanone) has [...] Read more.
Oxidative stress is closely linked to various diseases, and many studies have been conducted to determine how to reduce this stress. In particular, efforts are being made to find potential antioxidants from natural products. Studies have shown that raspberry ketone (RK; 4-(4-hydroxyphenyl)-2-butanone) has various pharmacological activities. This review summarizes the antioxidant activities of RK and their underlying mechanisms. In several experimental models, it was proven that RK exhibits antioxidant properties through increasing total antioxidant capacity (TAC); upregulating antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT); and improving lipid peroxidation. In conclusion, research about RK’s antioxidant activities is directly or indirectly related to its other various physiological activities. Further studies at the clinical level will be able to verify the value of RK as an effective antioxidant, functional health food, and therapeutic agent. Full article
(This article belongs to the Special Issue Antioxidants in Foods II)
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Article
Induction of AML Preleukemic Fusion Genes in HSPCs and DNA Damage Response in Preleukemic Fusion Gene Positive Samples
Antioxidants 2021, 10(3), 481; https://doi.org/10.3390/antiox10030481 - 18 Mar 2021
Cited by 2 | Viewed by 925
Abstract
Preleukemic fusion genes (PFGs) occurring after DNA damage in hematopoietic stem progenitor cells (HSPCs) in utero often represent the initial event in the development of childhood leukemia. While the incidence of PFGs characteristic for acute lymphoblastic leukemia (ALL) was relatively well examined by [...] Read more.
Preleukemic fusion genes (PFGs) occurring after DNA damage in hematopoietic stem progenitor cells (HSPCs) in utero often represent the initial event in the development of childhood leukemia. While the incidence of PFGs characteristic for acute lymphoblastic leukemia (ALL) was relatively well examined by several research groups and estimated to be 1–5% in umbilical cord blood (UCB) of healthy newborns, PFGs that are relevant to acute myeloid leukemia (AML) were poorly investigated. Therefore, this study is focused on the estimation of the incidence of the most frequent AML PFGs in newborns. For the first time, this study considered the inducibility of AML PFGs in different subsets of UCB HSPCs by low-dose γ-rays and also compared endogenous DNA damage, apoptosis, and reactive oxygen species (ROS) level between UCB samples containing or lacking AML PFGs. We found that: (i) the incidence of AML PFGs in UCB was 3.19% for RUNX1-RUNX1T1, 3.19% for PML-RARα, and 1.17% for KMT2A-MLLT3, (ii) 50 cGy of γ-rays did not induce RUNX1-RUNX1T1, PML-RARα, or KMT2A-MLLT3 PFGs in different subsets of sorted and expanded HSPCs, and (iii) the AML PFG+ samples accumulated the same level of endogenous DNA damage, as measured by the γH2AX/53BP1 focus formation, and also the same ROS level, and apoptosis as compared to PFG controls. Our study provides critical insights into the prevalence of AML PFGs in UCB of newborns, without the evidence of a specific HSPC population more susceptible for PFG formation after irradiation to low-dose γ-rays or increased amount of ROS, apoptosis and DNA damage. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS), Haematopoiesis and Leukaemia)
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Review
The Influence of Plant Extracts and Phytoconstituents on Antioxidant Enzymes Activity and Gene Expression in the Prevention and Treatment of Impaired Glucose Homeostasis and Diabetes Complications
Antioxidants 2021, 10(3), 480; https://doi.org/10.3390/antiox10030480 - 18 Mar 2021
Cited by 2 | Viewed by 1873
Abstract
Diabetes is a complex metabolic disorder resulting either from insulin resistance or an impaired insulin secretion. Prolonged elevated blood glucose concentration, the key clinical sign of diabetes, initiates an enhancement of reactive oxygen species derived from glucose autoxidation and glycosylation of proteins. Consequently, [...] Read more.
Diabetes is a complex metabolic disorder resulting either from insulin resistance or an impaired insulin secretion. Prolonged elevated blood glucose concentration, the key clinical sign of diabetes, initiates an enhancement of reactive oxygen species derived from glucose autoxidation and glycosylation of proteins. Consequently, chronic oxidative stress overwhelms cellular endogenous antioxidant defenses and leads to the acute and long-standing structural and functional changes of macromolecules resulting in impaired cellular functioning, cell death and organ dysfunction. The oxidative stress provoked chain of pathological events over time cause diabetic complications such as nephropathy, peripheral neuropathy, cardiomyopathy, retinopathy, hypertension, and liver disease. Under diabetic conditions, accompanying genome/epigenome and metabolite markers alterations may also affect glucose homeostasis, pancreatic β-cells, muscle, liver, and adipose tissue. By providing deeper genetic/epigenetic insight of direct or indirect dietary effects, nutrigenomics offers a promising opportunity to improve the quality of life of diabetic patients. Natural plant extracts, or their naturally occurring compounds, were shown to be very proficient in the prevention and treatment of different pathologies associated with oxidative stress including diabetes and its complications. Considering that food intake is one of the crucial components in diabetes’ prevalence, progression and complications, this review summarizes the effect of the major plant secondary metabolite and phytoconstituents on the antioxidant enzymes activity and gene expression under diabetic conditions. Full article
(This article belongs to the Special Issue Nutrigenomics and Antioxidant Components of Diet)
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Article
Protective Effects of Taurine Chloramine on Experimentally Induced Colitis: NFκB, STAT3, and Nrf2 as Potential Targets
Antioxidants 2021, 10(3), 479; https://doi.org/10.3390/antiox10030479 - 18 Mar 2021
Cited by 3 | Viewed by 1469
Abstract
Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory [...] Read more.
Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory mediators, such as chemokines and cytokines in many different types of cells. In the present study, we investigated the protective effects of TauCl on experimentally induced colon inflammation. Oral administration of TauCl protected against mouse colitis caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TauCl administration attenuated apoptosis in the colonic mucosa of TNBS-treated mice. This was accompanied by reduced expression of an oxidative stress marker, 4-hydroxy-2-nonenal and proinflammatory molecules including tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 in mouse colon. TauCl also inhibited activation of NFκB and STAT3, two key transcription factors mediating proinflammatory signaling. Notably, the protective effect of TauCl on oxidative stress and inflammation in the colon of TNBS-treated mice was associated with elevated activation of Nrf2 and upregulation of its target genes encoding heme oxygenase-1, NAD(P)H:quinone oxidoreductase, glutamate cysteine ligase catalytic subunit, and glutathione S-transferase. Taken together, these results suggest that TauCl exerts the protective effect against colitis through upregulation of Nrf2-dependent cytoprotective gene expression while blocking the proinflammatory signaling mediated by NFκB and STAT3. Full article
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Article
Effect of Maternal Dietary Redox Levels on Antioxidative Status and Immunity of the Suckling Off-Spring
Antioxidants 2021, 10(3), 478; https://doi.org/10.3390/antiox10030478 - 17 Mar 2021
Cited by 3 | Viewed by 871
Abstract
This study investigates two levels of dietary selenium (Se) and vitamin E in combination on their status in sows and their progeny, and influence on antioxidant status and immunological responses of the piglets at weaning. Female pigs (n = 6) were provided [...] Read more.
This study investigates two levels of dietary selenium (Se) and vitamin E in combination on their status in sows and their progeny, and influence on antioxidant status and immunological responses of the piglets at weaning. Female pigs (n = 6) were provided LOW or HIGH antioxidant nutrition (Se and vitamin E) from mating until weaning of their off-spring. The HIGH treatment elevated the concentration of Se (p = 0.015) and α-tocopherol (p = 0.023) in plasma of piglets compared with piglets of the LOW treatment. Treatments also affected the concentrations of milk and sow plasma immunoglobulins. Piglets from sows on the HIGH treatment had increased (p < 0.001) activity of glutathione peroxidase, lower serum levels of C-reactive protein (p = 0.005), haptoglobin (p = 0.05) and albumin (p = 0.05), and the number of white blood cells (p = 0.023) and the ratio of NEU to LYM was lower (p = 0.025) than in piglets from sows on the LOW group. Furthermore, the dietary antioxidant level influenced responses of cytokines (interleukine (IL) 6 (p = 0.007), 12 (p = 0.01) and 18 (p = 0.01)) in piglets’ plasma. In conclusion, improved antioxidant status via dietary maternal provision improves the robustness of the offspring via immunomodulatory mechanisms. Full article
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Article
NOX4 Mediates Pseudomonas aeruginosa-Induced Nuclear Reactive Oxygen Species Generation and Chromatin Remodeling in Lung Epithelium
Antioxidants 2021, 10(3), 477; https://doi.org/10.3390/antiox10030477 - 17 Mar 2021
Cited by 9 | Viewed by 1241
Abstract
Pseudomonas aeruginosa (PA) infection increases reactive oxygen species (ROS), and earlier, we have shown a role for NADPH oxidase-derived ROS in PA-mediated lung inflammation and injury. Here, we show a role for the lung epithelial cell (LEpC) NOX4 in PA [...] Read more.
Pseudomonas aeruginosa (PA) infection increases reactive oxygen species (ROS), and earlier, we have shown a role for NADPH oxidase-derived ROS in PA-mediated lung inflammation and injury. Here, we show a role for the lung epithelial cell (LEpC) NOX4 in PA-mediated chromatin remodeling and lung inflammation. Intratracheal administration of PA to Nox4flox/flox mice for 24 h caused lung inflammatory injury; however, epithelial cell-deleted Nox4 mice exhibited reduced lung inflammatory injury, oxidative stress, secretion of pro-inflammatory cytokines, and decreased histone acetylation. In LEpCs, NOX4 was localized both in the cytoplasmic and nuclear fractions, and PA stimulation increased the nuclear NOX4 expression and ROS production. Downregulation or inhibition of NOX4 and PKC δ attenuated the PA-induced nuclear ROS. PA-induced histone acetylation was attenuated by Nox4-specific siRNA, unlike Nox2. PA stimulation increased HDAC1/2 oxidation and reduced HDAC1/2 activity. The PA-induced oxidation of HDAC2 was attenuated by N-acetyl-L-cysteine and siRNA specific for Pkc δ, Sphk2, and Nox4. PA stimulated RAC1 activation in the nucleus and enhanced the association between HDAC2 and RAC1, p-PKC δ, and NOX4 in LEpCs. Our results revealed a critical role for the alveolar epithelial NOX4 in mediating PA-induced lung inflammatory injury via nuclear ROS generation, HDAC1/2 oxidation, and chromatin remodeling. Full article
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Article
Curcumin Ameliorated Oxidative Stress and Inflammation-Related Muscle Disorders in C2C12 Myoblast Cells
Antioxidants 2021, 10(3), 476; https://doi.org/10.3390/antiox10030476 - 17 Mar 2021
Cited by 4 | Viewed by 1190
Abstract
The purpose of the current study was to investigate antioxidant and anti-inflammatory effects of spray dry powder containing 40% curcumin (CM-SD) in C2C12 myoblast cells. CM-SD increased DPPH radical scavenging activity in a dose-dependent manner, and up to 30 μg/mL of CM-SD did [...] Read more.
The purpose of the current study was to investigate antioxidant and anti-inflammatory effects of spray dry powder containing 40% curcumin (CM-SD) in C2C12 myoblast cells. CM-SD increased DPPH radical scavenging activity in a dose-dependent manner, and up to 30 μg/mL of CM-SD did not express cytotoxicity in C2C12 cells. Exposure to hydrogen peroxide (H2O2) drastically decreased the viability of C2C12 cells, but pre-treatment of CM-SD significantly increased the cell viability (p < 0.01). CM-SD significantly transactivated the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent luciferase activity in a dose-dependent manner and enhanced the levels of heme oxygenase (HO)-1, glutamate cysteine ligase catalytic subunit (GCLC), and NAD(P)H-dependent quinone oxidoreductase (NQO)-1. CM-SD also significantly reduced reactive oxygen species (ROS) production and lipid peroxidation and restored glutathione (GSH) depletion in H2O2-treated C2C12 cells. Moreover, CM-SD significantly reduced lipopolysaccharides (LPS)-mediated interleukin (IL)-6 production in the conditioned medium. Results from the current study suggest that CM-SD could be a useful candidate against oxidative stress and inflammation-related muscle disorders. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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Article
Auraptene Enhances Junction Assembly in Cerebrovascular Endothelial Cells by Promoting Resilience to Mitochondrial Stress through Activation of Antioxidant Enzymes and mtUPR
Antioxidants 2021, 10(3), 475; https://doi.org/10.3390/antiox10030475 - 17 Mar 2021
Cited by 1 | Viewed by 1064
Abstract
Junctional proteins in cerebrovascular endothelial cells are essential for maintaining the barrier function of the blood-brain barrier (BBB), thus protecting the brain from the infiltration of pathogens. The present study showed that the potential therapeutic natural compound auraptene (AUR) enhances junction assembly in [...] Read more.
Junctional proteins in cerebrovascular endothelial cells are essential for maintaining the barrier function of the blood-brain barrier (BBB), thus protecting the brain from the infiltration of pathogens. The present study showed that the potential therapeutic natural compound auraptene (AUR) enhances junction assembly in cerebrovascular endothelial cells by inducing antioxidant enzymes and the mitochondrial unfolded protein response (mtUPR). Treatment of mouse cerebrovascular endothelial cells with AUR enhanced the expression of junctional proteins, such as occludin, zonula occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin), by increasing the levels of mRNA encoding antioxidant enzymes. AUR treatment also resulted in the depolarization of mitochondrial membrane potential and activation of mtUPR. The ability of AUR to protect against ischemic conditions was further assessed using cells deprived of oxygen and glucose. Pretreatment of these cells with AUR protected against damage to junctional proteins, including occludin, claudin-5, ZO-1 and VE-cadherin, accompanied by a stress resilience response regulated by levels of ATF5, LONP1 and HSP60 mRNAs. Collectively, these results indicate that AUR promotes resilience against oxidative stress and improves junction assembly, suggesting that AUR may help maintain intact barriers in cerebrovascular endothelial cells. Full article
(This article belongs to the Special Issue Natural Antioxidant in Cardiovascular and Cerebrovascular Diseases)
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Article
Allysine and α-Aminoadipic Acid as Markers of the Glyco-Oxidative Damage to Human Serum Albumin under Pathological Glucose Concentrations
Antioxidants 2021, 10(3), 474; https://doi.org/10.3390/antiox10030474 - 17 Mar 2021
Cited by 3 | Viewed by 1008
Abstract
Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such [...] Read more.
Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such as diabetes. Allysine as well as its oxidation product, the α-amino adipic acid (α-AA) have been found to be markers of diabetes risk whereas little is known about the chemistry involved in its formation under hyperglycemic conditions. To provide insight into this issue, human serum albumin was incubated in the presence of FeCl3 (25 μM) and increasing glucose concentrations for 32 h at 37 °C. These concentrations were selected to simulate (i) physiological fasting plasma concentration (4 mM), (ii) pathological pre-diabetes fasting plasma concentration (8 mM), and pathological diabetes fasting plasma concentration (12 mM) of glucose. While both allysine and α-AA were found to increase with increasing glucose concentrations, the carboxylic acid was only detected at pathological glucose concentrations and appeared to be a more reliable indicator of glyco-oxidative stress. The underlying chemical mechanisms of lysine glycation as well as of the depletion of tryptophan and formation of fluorescent and colored advanced glycation products are discussed. Full article
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Article
High Fruit and Vegetable Consumption and Moderate Fat Intake Are Associated with Higher Carotenoid Concentration in Human Plasma
Antioxidants 2021, 10(3), 473; https://doi.org/10.3390/antiox10030473 - 17 Mar 2021
Cited by 2 | Viewed by 2337
Abstract
Carotenoids are pigments contained mainly in fruit and vegetables (F&V) that have beneficial effects on cardiometabolic health. Due to their lipophilic nature, co-ingestion of fat appears to increase their bioavailability via facilitating transfer to the aqueous micellar phase during digestion. However, the extent [...] Read more.
Carotenoids are pigments contained mainly in fruit and vegetables (F&V) that have beneficial effects on cardiometabolic health. Due to their lipophilic nature, co-ingestion of fat appears to increase their bioavailability via facilitating transfer to the aqueous micellar phase during digestion. However, the extent to which high fat intake may contribute to increased carotenoid plasma concentrations is still unclear. The objective was to examine the degree to which the consumption of different amounts of both carotenoid-rich foods and fats is associated with plasma carotenoid concentrations within a Mediterranean lifestyle context (subsample from the PREDIMED-Plus study baseline) where consumption of F&V and fat is high. The study population was categorized into four groups according to their self-reported consumption of F&V and fat. Carotenoids were extracted from plasma samples and analyzed by HPLC-UV-VIS-QqQ-MS/MS. Carotenoid systemic concentrations were greater in high consumers of F&V than in low consumers of these foods (+3.04 μmol/L (95% CI: 0.90, 5.17), p-value = 0.005), but circulating concentrations seemed to decrease when total fat intake was very high (−2.69 μmol/L (−5.54; 0.16), p-value = 0.064). High consumption of F&V is associated with greater systemic levels of total carotenoids, in particular when fat intake is low-to-moderate rather than very high. Full article
(This article belongs to the Special Issue Dietary Antioxidants in Mediterranean Diet)
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Article
Chemical Properties of Vitis Vinifera Carménère Pomace Extracts Obtained by Hot Pressurized Liquid Extraction, and Their Inhibitory Effect on Type 2 Diabetes Mellitus Related Enzymes
Antioxidants 2021, 10(3), 472; https://doi.org/10.3390/antiox10030472 - 17 Mar 2021
Cited by 6 | Viewed by 1577
Abstract
Grape pomace polyphenols inhibit Type 2 Diabetes Mellitus (T2DM)-related enzymes, reinforcing their sustainable recovery to be used as an alternative to the synthetic drug acarbose. Protic co-solvents (ethanol 15% and glycerol 15%) were evaluated in the hot pressurized liquid extraction (HPLE) of Carménère [...] Read more.
Grape pomace polyphenols inhibit Type 2 Diabetes Mellitus (T2DM)-related enzymes, reinforcing their sustainable recovery to be used as an alternative to the synthetic drug acarbose. Protic co-solvents (ethanol 15% and glycerol 15%) were evaluated in the hot pressurized liquid extraction (HPLE) of Carménère pomace at 90, 120, and 150 °C in order to obtain extracts rich in monomers and oligomers of procyanidins with high antioxidant capacities and inhibitory effects on α-amylase and α-glucosidase. The higher the HPLE temperature (from 90 °C to 150 °C) the higher the total polyphenol content (~79%, ~83%, and ~143% for water-ethanol, water-glycerol and pure water, respectively) and antioxidant capacity of the extracts (Oxygen Radical Absorbance Capacity, ORAC), increased by ~26%, 27% and 13%, while the half maximal inhibitory concentration (IC50) decreased by ~65%, 67%, and 59% for water-ethanol, water-glycerol, and pure water extracts, respectively). Water-glycerol HPLE at 150 and 120 °C recovered the highest amounts of monomers (99, 421, and 112 µg/g dw of phenolic acids, flavanols, and flavonols, respectively) and dimers of procyanidins (65 and 87 µg/g dw of B1 and B2, respectively). At 90 °C, the water-ethanol mixture extracted the highest amounts of procyanidin trimers (13 and 49 µg/g dw of C1 and B2, respectively) and procyanidin tetramers of B2 di-O-gallate (13 µg/g dw). Among the Carménère pomace extracts analyzed in this study, 1000 µg/mL of the water-ethanol extract obtained, at 90 °C, reduced differentially the α-amylase (56%) and α-glucosidase (98%) activities. At the same concentration, acarbose inhibited 56% of α-amylase and 73% of α-glucosidase activities; thus, our grape HPLE extracts can be considered a good inhibitor compared to the synthetic drug. Full article
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Article
Deletion of Superoxide Dismutase 1 Blunted Inflammatory Aortic Remodeling in Hypertensive Mice under Angiotensin II Infusion
Antioxidants 2021, 10(3), 471; https://doi.org/10.3390/antiox10030471 - 16 Mar 2021
Cited by 2 | Viewed by 770
Abstract
Superoxide dismutase (SOD) is an enzyme that catalyzes the dismutation of two superoxide anions (O2·−) into hydrogen peroxide (H2O2) and oxygen (O2) and is generally known to protect against oxidative stress. Angiotensin II (AngII) [...] Read more.
Superoxide dismutase (SOD) is an enzyme that catalyzes the dismutation of two superoxide anions (O2·−) into hydrogen peroxide (H2O2) and oxygen (O2) and is generally known to protect against oxidative stress. Angiotensin II (AngII) causes vascular hypertrophic remodeling which is associated with H2O2 generation. The aim of this study is to investigate the role of cytosolic SOD (SOD1) in AngII-induced vascular hypertrophy. We employed C57/BL6 mice (WT) and SOD1 deficient mice (SOD1−/−) with the same background. They received a continuous infusion of saline or AngII (3.2 mg/kg/day) for seven days. The blood pressures were equally elevated at 1.5 times with AngII, however, vascular hypertrophy was blunted in SOD1−/− mice compared to WT mice (WT mice 91.9 ± 1.13 µm versus SOD1−/− mice 68.4 ± 1.41 µm p < 0.001). The elevation of aortic interleukin 6 (IL-6) and phosphorylation of pro-inflammatory STAT3 due to AngII were also blunted in SOD1−/− mice’s aortas. In cultured rat vascular smooth muscle cells (VSMCs), reducing expression of SOD1 with siRNA decreased AngII induced IL-6 release as well as phosphorylation of STAT3. Pre-incubation with polyethylene glycol (PEG)-catalase also attenuated phosphorylation of STAT3 due to AngII. These results indicate that SOD1 in VSMCs plays a role in vascular hypertrophy due to increased inflammation caused by AngII, probably via the production of cytosolic H2O2. Full article
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