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Antioxidants, Volume 10, Issue 1 (January 2021) – 138 articles

Cover Story (view full-size image): The enzyme CYP1A2 is responsible for the metabolism of caffeine into paraxanthine. Both molecules are known for their antioxidant and pro-oxidant characteristics, and the paraxanthine-to-caffeine molar ratio is a widely accepted metric for CYP1A2 phenotyping for optimizing dose–response effects in individual patients. This work presents the simultaneous quantification of caffeine and paraxanthine in spiked human saliva samples by differential pulse voltammetry using an anodically pretreated glassy carbon electrode. Potential applicability of the sensing platform was demonstrated by running a small-scale trial on five healthy volunteers. The results were validated by ultra-high-pressure liquid chromatography and shown to have a high correlation factor (r = 0.994). View this paper
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Open AccessArticle
Microdose Lithium Protects against Pancreatic Islet Destruction and Renal Impairment in Streptozotocin-Elicited Diabetes
Antioxidants 2021, 10(1), 138; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010138 - 19 Jan 2021
Viewed by 594
Abstract
Psychiatric use of lithium has been associated with hypoglycemic effects, but its effect on type 1 diabetes mellitus (T1D) is unknown. In streptozotocin (STZ) induced murine models of T1D, microdose lithium therapy improved hyperglycemia, attenuated body weight loss and prevented early signs of [...] Read more.
Psychiatric use of lithium has been associated with hypoglycemic effects, but its effect on type 1 diabetes mellitus (T1D) is unknown. In streptozotocin (STZ) induced murine models of T1D, microdose lithium therapy improved hyperglycemia, attenuated body weight loss and prevented early signs of diabetic kidney injury. This beneficial effect was associated with preservation of pancreatic islet histology and β-cell production of insulin as well as mitigated oxidative damage of islets. Mechanistically, lithium in islets cells induced inhibitory phosphorylation of glycogen synthase kinase 3β (GSK3β), the major molecular target of lithium that has been recently implicated in non-canonical regulation of Nrf2 activity. In turn, Nrf2 antioxidant response was potentiated in islets, marked by nuclear translocation of Nrf2 and augmented expression of its target antioxidant enzyme heme oxygenase 1 (HO-1). Conversely, cotreatment with trigonelline, a selective blockade of Nrf2, offset the lithium enhanced Nrf2 antioxidant response in islets, blunted the protective effect of lithium on pancreatic islets and β-cells, and abolished the hypoglycemic activity of lithium in STZ-injured mice. Collectively, our findings suggest that microdose lithium confers a protective effect on islet β-cells via targeting the GSK3β-regulated Nrf2 antioxidant response and thereby ameliorates T1D and its related kidney impairment. Full article
(This article belongs to the Special Issue Role of Natural Antioxidants in Free Radical Biology and Human Health)
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Open AccessArticle
Assessment of the Telomere Length and Its Effect on the Symptomatology of Parkinson’s Disease
Antioxidants 2021, 10(1), 137; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010137 - 19 Jan 2021
Viewed by 451
Abstract
Telomeres, which are repetitive sequences that cap the end of the chromosomes, shorten with each cell division. Besides cellular aging, there are several other factors that influence telomere length (TL), in particular, oxidative stress and inflammation, which play an important role in the [...] Read more.
Telomeres, which are repetitive sequences that cap the end of the chromosomes, shorten with each cell division. Besides cellular aging, there are several other factors that influence telomere length (TL), in particular, oxidative stress and inflammation, which play an important role in the pathogenesis of neurodegenerative brain diseases including Parkinson’s disease (PD). So far, the majority of studies have not demonstrated a significant difference in TL between PD patients and healthy individuals. However, studies investigating the effect of TL on the symptomatology and disease progression of PD are scarce, and thus, warranted. We analyzed TL of peripheral blood cells in a sample of 204 PD patients without concomitant autoimmune diseases and analyzed its association with several PD related phenotypes. Monochrome multiplex quantitative PCR (mmqPCR) was used to determine relative TL given as a ratio of the amount of DNA between the telomere and albumin as the housekeeping gene. We found a significant difference in the relative TL between PD patients with and without dementia, where shorter TL presented higher risk for dementia (p = 0.024). However, the correlation was not significant after adjustment for clinical factors (p = 0.509). We found no correlations between TLs and the dose of dopaminergic therapy when the analysis was adjusted for genetic variability in inflammatory or oxidative factors. In addition, TL influenced time to onset of motor complications after levodopa treatment initiation (p = 0.0134), but the association did not remain significant after adjustment for age at inclusion and disease duration (p = 0.0781). Based on the results of our study we conclude that TL contributes to certain PD-related phenotypes, although it may not have a major role in directing the course of the disease. Nevertheless, this expends currently limited knowledge regarding the association of the telomere attrition and the disease severity or motor complications in Parkinson’s disease. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in the Nervous System)
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Open AccessArticle
Vacuole and Mitochondria Patch (vCLAMP) Protein Vam6 Is Involved in Maintenance of Mitochondrial and Vacuolar Functions under Oxidative Stress in Candida albicans
Antioxidants 2021, 10(1), 136; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010136 - 19 Jan 2021
Viewed by 435
Abstract
Candida albicans is one of the most common opportunistic fungal pathogens in human beings. When infecting host cells, C. albicans is often exposed to oxidative stress from the host immune defense system. Maintenance of mitochondrial and vacuolar functions is crucial for its resistance [...] Read more.
Candida albicans is one of the most common opportunistic fungal pathogens in human beings. When infecting host cells, C. albicans is often exposed to oxidative stress from the host immune defense system. Maintenance of mitochondrial and vacuolar functions is crucial for its resistance to oxidative stress. However, the role of vacuole and mitochondria patchs (vCLAMPs) in cellular oxidative stress resistance and in the maintenance of organelle functions remains to be elucidated. Herein, the function of the vCLAMP protein Vam6 in response to oxidative stress was explored. The results showed that the vam6∆/∆ mutant exhibited obvious mitochondrial swelling, mtDNA damage, reduced activity of antioxidant enzymes, and abnormal vacuolar morphology under H2O2 treatment, indicating its important role in maintaining the structures and functions of both mitochondria and vacuoles under oxidative stress. Further studies showed that deletion of VAM6 attenuated hyphal development under oxidative stress. Moreover, loss of Vam6 obviously affected host tissue invasion and virulence of C. albicans. Taken together, this paper reveals the critical role of vCLAMPs in response to oxidative stress in C. albicans. Full article
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Open AccessArticle
The Positive Allosteric Modulation of alpha7-Nicotinic Cholinergic Receptors by GAT107 Increases Bacterial Lung Clearance in Hyperoxic Mice by Decreasing Oxidative Stress in Macrophages
Antioxidants 2021, 10(1), 135; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010135 - 19 Jan 2021
Viewed by 414
Abstract
Supplemental oxygen therapy with supraphysiological concentrations of oxygen (hyperoxia; >21% O2) is a life-saving intervention for patients experiencing respiratory distress. However, prolonged exposure to hyperoxia can compromise bacterial clearance processes, due to oxidative stress-mediated impairment of macrophages, contributing to the increased [...] Read more.
Supplemental oxygen therapy with supraphysiological concentrations of oxygen (hyperoxia; >21% O2) is a life-saving intervention for patients experiencing respiratory distress. However, prolonged exposure to hyperoxia can compromise bacterial clearance processes, due to oxidative stress-mediated impairment of macrophages, contributing to the increased susceptibility to pulmonary infections. This study reports that the activation of the α7 nicotinic acetylcholine receptor (α7nAChR) with the delete allosteric agonistic-positive allosteric modulator, GAT107, decreases the bacterial burden in mouse lungs by improving hyperoxia-induced lung redox imbalance. The incubation of RAW 264.7 cells with GAT107 (3.3 µM) rescues hyperoxia-compromised phagocytic functions in cultured macrophages, RAW 264.7 cells, and primary bone marrow-derived macrophages. Similarly, GAT107 (3.3 µM) also attenuated oxidative stress in hyperoxia-exposed macrophages, which prevents oxidation and hyper-polymerization of phagosome filamentous actin (F-actin) from oxidation. Furthermore, GAT107 (3.3 µM) increases the (1) activity of superoxide dismutase 1; (2) activation of Nrf2 and (3) the expression of heme oxygenase-1 (HO-1) in macrophages exposed to hyperoxia. Overall, these data suggest that the novel α7nAChR compound, GAT107, could be used to improve host defense functions in patients, such as those with COVID-19, who are exposed to prolonged periods of hyperoxia. Full article
(This article belongs to the Special Issue Antioxidants and Lung Diseases)
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Open AccessArticle
Pro-Resolving FPR2 Agonists Regulate NADPH Oxidase-Dependent Phosphorylation of HSP27, OSR1, and MARCKS and Activation of the Respective Upstream Kinases
Antioxidants 2021, 10(1), 134; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010134 - 19 Jan 2021
Viewed by 369
Abstract
Background: Formyl peptide receptor 2 (FPR2) is involved in the pathogenesis of chronic inflammatory diseases, being activated either by pro-resolving or proinflammatory ligands. FPR2-associated signal transduction pathways result in phosphorylation of several proteins and in NADPH oxidase activation. We, herein, investigated molecular mechanisms [...] Read more.
Background: Formyl peptide receptor 2 (FPR2) is involved in the pathogenesis of chronic inflammatory diseases, being activated either by pro-resolving or proinflammatory ligands. FPR2-associated signal transduction pathways result in phosphorylation of several proteins and in NADPH oxidase activation. We, herein, investigated molecular mechanisms underlying phosphorylation of heat shock protein 27 (HSP27), oxidative stress responsive kinase 1 (OSR1), and myristolated alanine-rich C-kinase substrate (MARCKS) elicited by the pro-resolving FPR2 agonists WKYMVm and annexin A1 (ANXA1). Methods: CaLu-6 cells or p22phoxCrispr/Cas9 double nickase CaLu-6 cells were incubated for 5 min with WKYMVm or ANXA1, in the presence or absence of NADPH oxidase inhibitors. Phosphorylation at specific serine residues of HSP27, OSR1, and MARCKS, as well as the respective upstream kinases activated by FPR2 stimulation was analysed. Results: Blockade of NADPH oxidase functions prevents WKYMVm- and ANXA1-induced HSP-27(Ser82), OSR1(Ser339) and MARCKS(Ser170) phosphorylation. Moreover, NADPH oxidase inhibitors prevent WKYMVm- and ANXA1-dependent activation of p38MAPK, PI3K and PKCδ, the kinases upstream to HSP-27, OSR1 and MARCKS, respectively. The same results were obtained in p22phoxCrispr/Cas9 cells. Conclusions: FPR2 shows an immunomodulatory role by regulating proinflammatory and anti-inflammatory activities and NADPH oxidase is a key regulator of inflammatory pathways. The activation of NADPH oxidase-dependent pro-resolving downstream signals suggests that FPR2 signalling and NADPH oxidase could represent novel targets for inflammation therapeutic intervention. Full article
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Open AccessArticle
(−)-Epicatechin—An Important Contributor to the Antioxidant Activity of Japanese Knotweed Rhizome Bark Extract as Determined by Antioxidant Activity-Guided Fractionation
Antioxidants 2021, 10(1), 133; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010133 - 18 Jan 2021
Cited by 1 | Viewed by 540
Abstract
The antioxidant activities of Japanese knotweed rhizome bark extracts, prepared with eight different solvents or solvent mixtures (water, methanol, 80% methanol(aq), acetone, 70% acetone(aq), ethanol, 70% ethanol(aq), and 90% ethyl acetate(aq)), were determined using a [...] Read more.
The antioxidant activities of Japanese knotweed rhizome bark extracts, prepared with eight different solvents or solvent mixtures (water, methanol, 80% methanol(aq), acetone, 70% acetone(aq), ethanol, 70% ethanol(aq), and 90% ethyl acetate(aq)), were determined using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay. Low half maximal inhibitory concentration (IC50) values (2.632–3.720 µg mL−1) for all the extracts were in the range of the IC50 value of the known antioxidant ascorbic acid at t0 (3.115 µg mL−1). Due to the highest extraction yield (~44%), 70% ethanol(aq) was selected for the preparation of the extract for further investigations. The IC50 value calculated for its antioxidant activity remained stable for at least 14 days, while the IC50 of ascorbic acid increased over time. The stability study showed that the container material was of great importance for the light-protected storage of the ascorbic acid(aq) solution in a refrigerator. Size exclusion–high-performance liquid chromatography (SEC-HPLC)–UV and reversed phase (RP)-HPLC-UV coupled with multistage mass spectrometry (MSn) were developed for fractionation of the 70% ethanol(aq) extract and for further compound identification, respectively. In the most potent antioxidant SEC fraction, determined using an on-line post-column SEC-HPLC-DPPH assay, epicatechin, resveratrol malonyl hexoside, and its in-source fragments (resveratrol and resveratrol acetyl hexoside) were tentatively identified by RP-HPLC-MSn. Moreover, epicatechin was additionally confirmed by two orthogonal methods, SEC-HPLC-UV and high-performance thin-layer chromatography (HPTLC) coupled with densitometry. Finally, the latter technique enabled the identification of (−)-epicatechin. (−)-Epicatechin demonstrated potent and stable time-dependent antioxidant activity (IC50 value ~1.5 µg mL−1) for at least 14 days. Full article
(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection)
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Open AccessArticle
Oxidised LDL and Anti-Oxidised LDL Antibodies Are Reduced by Lipoprotein Apheresis in a Randomised Controlled Trial on Patients with Refractory Angina and Elevated Lipoprotein(a)
Antioxidants 2021, 10(1), 132; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010132 - 18 Jan 2021
Viewed by 462
Abstract
Aims: An abundance of epidemiological evidence demonstrates that elevated lipoprotein(a) (Lp(a)) represents a significant contributing risk factor towards the development of cardiovascular disease. In particular, raised Lp(a) may play a mechanistic role in patients with refractory angina. Studies have also shown a correlation [...] Read more.
Aims: An abundance of epidemiological evidence demonstrates that elevated lipoprotein(a) (Lp(a)) represents a significant contributing risk factor towards the development of cardiovascular disease. In particular, raised Lp(a) may play a mechanistic role in patients with refractory angina. Studies have also shown a correlation between oxidised LDL (oxLDL) levels and atherosclerotic burden as well as rates of cardiovascular events. Antibodies against oxLDL (anti-oxLDL) are involved in the removal of oxLDL. Lipoprotein apheresis (LA), which removes lipoproteins using extra-corporeal processes, is an established means of reducing Lp(a), and thereby reduces cardiovascular events. The aim of this study was to investigate the effect of LA on oxLDL and anti-oxLDL levels amongst those with refractory angina in the context of raised Lp(a). Methods: We performed a sub-study within a randomised controlled crossover trial involving 20 patients with refractory angina and raised Lp(a) > 500 mg/L, comparing the effect of three months of blinded weekly LA or sham, followed by crossover to the opposite study arm. We utilized enzyme-linked immunosorbent assays (ELISA) to quantify oxLDL and IgG/ IgM anti-oxLDL antibody levels at baseline and following three months of active LA or sham sessions. Results: Following three months of LA, there was a 30% reduction in oxLDL from 0.37 ± 0.06 to 0.26 ± 0.04 with a mean drop of −0.11 units (U) (95% CI −0.13, −0.09) compared to no significant change with sham therapy (p < 0.0001 between treatment arms). LA also led to a 22% reduction in levels of IgG and IgM anti-oxLDL, again with no significant change demonstrated during sham (p = 0.0036 and p = 0.012, respectively, between treatment arms). Conclusion: Amongst patients with refractory angina in the context of elevated Lp(a), LA significantly lowers levels of oxLDL and anti-oxLDL antibodies, representing potential mechanisms by which LA yields symptomatic and prognostic benefits in this patient cohort. Full article
(This article belongs to the Special Issue Role of Lipoprotein Oxidation in Various Diseases)
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Open AccessFeature PaperArticle
Preharvest Methyl Jasmonate Treatment Increased the Antioxidant Activity and Glucosinolate Contents of Hydroponically Grown Pak Choi
Antioxidants 2021, 10(1), 131; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010131 - 18 Jan 2021
Viewed by 526
Abstract
Vertical hydroponics farming has emerged as an alternative solution to feed the continuously growing world population. Additionally, recent studies reported that the exogenous treatments of jasmonic acid influence the phytochemical composition of Brassicaceae. We conducted this study to determine the effect of preharvest [...] Read more.
Vertical hydroponics farming has emerged as an alternative solution to feed the continuously growing world population. Additionally, recent studies reported that the exogenous treatments of jasmonic acid influence the phytochemical composition of Brassicaceae. We conducted this study to determine the effect of preharvest methyl jasmonate (MeJA) treatment on the phytochemical composition and antioxidant activities of soil- and hydroponically grown pak choi. An aqueous solution of 0.5-mM MeJA was sprayed to saturation on the aerial plant part three days before harvest. The harvested pak choi was freeze-dried and then powdered to measure the antioxidant activity and the contents of chlorophylls (Chls), total phenolics and flavonoids, and glucosinolates (GSLs). The overall results revealed that pak choi grown in vertical hydroponics had higher total Chls and total phenolics than those grown in soil in the greenhouse, regardless of MeJA treatment. Nevertheless, the GSLs content and total flavonoids increased significantly due to MeJA treatment in both growing systems, and the highest values were recorded in hydroponically grown MeJA-treated pak choi. Similarly, the 2, 2-di-phenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, Trolox-equivalent antioxidant capacity (ABTS), oxygen radical absorbance capacity (ORAC), and ferric-reducing antioxidant power (FRAP) were highest in hydroponically grown MeJA-treated pak choi. Taken together, the preharvest foliar treatment of MeJA can be used to improve the phytochemical composition of pak choi grown in both growing systems. Interestingly, the results strongly support the use of MeJA treatment in the vertical hydroponics growing system compared to the conventional growing system in the soil. This indicates that supplementing the vertical hydroponic growing system with preharvest MeJA treatment could be the best option to improve both the yield per square meter and the quality of pak choi. Besides, MeJA-treated pak choi could be used as a value-added horticultural commodity, as its antioxidant activity increased after treatment. Moreover, after further studies, MeJA could also be applied to other Brassica vegetables to improve their GSL contents and antioxidant properties. Full article
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Open AccessReview
Catalytic Antioxidants in the Kidney
Antioxidants 2021, 10(1), 130; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010130 - 18 Jan 2021
Viewed by 418
Abstract
Reactive oxygen species and reactive nitrogen species are highly implicated in kidney injuries that include acute kidney injury, chronic kidney disease, hypertensive nephropathy, and diabetic nephropathy. Therefore, antioxidant agents are promising therapeutic strategies for kidney diseases. Catalytic antioxidants are defined as small molecular [...] Read more.
Reactive oxygen species and reactive nitrogen species are highly implicated in kidney injuries that include acute kidney injury, chronic kidney disease, hypertensive nephropathy, and diabetic nephropathy. Therefore, antioxidant agents are promising therapeutic strategies for kidney diseases. Catalytic antioxidants are defined as small molecular mimics of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and some of them function as potent detoxifiers of lipid peroxides and peroxynitrite. Several catalytic antioxidants have been demonstrated to be effective in a variety of in vitro and in vivo disease models that are associated with oxidative stress, including kidney diseases. This review summarizes the evidence for the role of antioxidant enzymes in kidney diseases, the classifications of catalytic antioxidants, and their current applications to kidney diseases. Full article
(This article belongs to the Special Issue Catalytic Antioxidants)
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Open AccessArticle
The Influence of a Conjugated Pneumococcal Vaccination on Plasma Antibody Levels against Oxidized Low-Density Lipoprotein in Metabolic Disease Patients: A Single-Arm Pilot Clinical Trial
Antioxidants 2021, 10(1), 129; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010129 - 18 Jan 2021
Cited by 1 | Viewed by 413
Abstract
As a mediator between lipid metabolism dysfunction, oxidative stress and inflammation, oxidized low-density lipoprotein (oxLDL) is a promising therapeutical target in a wide range of metabolic diseases. In mice, pneumococcal immunization increases anti-phosphorylcholine and oxLDL antibody levels, and reduces atherosclerosis, non-alcoholic steatohepatitis and [...] Read more.
As a mediator between lipid metabolism dysfunction, oxidative stress and inflammation, oxidized low-density lipoprotein (oxLDL) is a promising therapeutical target in a wide range of metabolic diseases. In mice, pneumococcal immunization increases anti-phosphorylcholine and oxLDL antibody levels, and reduces atherosclerosis, non-alcoholic steatohepatitis and Niemann–Pick disease burden. These findings suggest that pneumococcal vaccination may be a useful preventive and therapeutical strategy in metabolic disease patients. In this pilot clinical trial, our aim was to determine whether the administration of a pneumococcal vaccine increases anti-phosphorylcholine and anti-oxLDL antibody levels in metabolic disease patients. The following patients were enrolled: four patients with familial partial lipodystrophy (all women, mean age 32 years old); three familial hypercholesterolemia patients (one girl, two boys; mean age 13 years); and two Niemann–Pick type B (NP-B) patients (two men, mean age 37.5 years old). Participants received one active dose of a 13-valent conjugated pneumococcal vaccine (Prevenar 13) and were followed-up for four weeks. Four weeks after Prevenar 13 vaccination, no differences were observed in patients’ levels of anti-oxLDL IgM or IgG antibodies. In addition, we observed a reduction in anti-phosphorylcholine (anti-PC) IgM antibody levels, whereas no differences were observed in anti-PC IgG antibody titers. These findings indicate that Prevenar 13 vaccination does not induce an immune response against oxLDL in patients with metabolic diseases. Therefore, Prevenar 13 is not suited to target the metabolic disruptor and pro-inflammatory mediator oxLDL in patients. Full article
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Open AccessReview
Comprehensive Review of Methodology to Detect Reactive Oxygen Species (ROS) in Mammalian Species and Establish Its Relationship with Antioxidants and Cancer
Antioxidants 2021, 10(1), 128; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010128 - 18 Jan 2021
Viewed by 612
Abstract
Evidence suggests that reactive oxygen species (ROS) mediate tissue homeostasis, cellular signaling, differentiation, and survival. ROS and antioxidants exert both beneficial and harmful effects on cancer. ROS at different concentrations exhibit different functions. This creates necessity to understand the relation between ROS, antioxidants, [...] Read more.
Evidence suggests that reactive oxygen species (ROS) mediate tissue homeostasis, cellular signaling, differentiation, and survival. ROS and antioxidants exert both beneficial and harmful effects on cancer. ROS at different concentrations exhibit different functions. This creates necessity to understand the relation between ROS, antioxidants, and cancer, and methods for detection of ROS. This review highlights various sources and types of ROS, their tumorigenic and tumor prevention effects; types of antioxidants, their tumorigenic and tumor prevention effects; and abnormal ROS detoxification in cancer; and methods to measure ROS. We conclude that improving genetic screening methods and bringing higher clarity in determination of enzymatic pathways and scale-up in cancer models profiling, using omics technology, would support in-depth understanding of antioxidant pathways and ROS complexities. Although numerous methods for ROS detection are developing very rapidly, yet further modifications are required to minimize the limitations associated with currently available methods. Full article
(This article belongs to the Special Issue Antioxidants and Cancer)
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Open AccessArticle
Antioxidant and Cytoprotective Potential of the Essential Oil Pistacia lentiscus var. chia and Its Major Components Myrcene and α-Pinene
Antioxidants 2021, 10(1), 127; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010127 - 18 Jan 2021
Viewed by 845
Abstract
The antioxidant, cytoprotective, and wound-healing potential of the essential oil from the resin of Pistacia lentiscus var. chia (mastic oil) was evaluated, along with that of its major components, myrcene and α-pinene. Antioxidant potential was monitored as: (i) direct antioxidant activity as [...] Read more.
The antioxidant, cytoprotective, and wound-healing potential of the essential oil from the resin of Pistacia lentiscus var. chia (mastic oil) was evaluated, along with that of its major components, myrcene and α-pinene. Antioxidant potential was monitored as: (i) direct antioxidant activity as assessed by 2,2-di-phenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and ABTS assays; (ii) DNA damage protection activity; and (iii) cytoprotective activity as assessed via induction of transcription of genes related to the antioxidant response in human keratinocyte cells (HaCaT). The cytoprotective potential of the test substances was further evaluated against ultraviolet radiation B (UVB)- or H2O2-induced oxidative damage, whereas their regenerative capability was accessed by monitoring the wound closure rate in HaCaT. Μastic oil and major components did not show significant direct antioxidant activity, however they increased the mRNA levels of antioxidant response genes, suggesting indirect antioxidant activity. Treatment of HaCaT with the test substances before and after UVB irradiation resulted in increased cell viability in the cases of pre-treatment with mastic oil or post-treatment with myrcene. Increased cytoprotection was also observed in the case of cell treatment with mastic oil or its major components prior to H2O2 exposure. Finally, mastic oil and myrcene demonstrated a favorable dose-dependent effect for cell migration and wound closure. Collectively, mastic essential oil may exert its promising cytoprotective properties through indirect antioxidant mechanisms. Full article
(This article belongs to the Special Issue Feature Papers in Antioxidants in 2020)
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Open AccessReview
The Multifaced Actions of Curcumin in Pregnancy Outcome
Antioxidants 2021, 10(1), 126; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010126 - 17 Jan 2021
Viewed by 553
Abstract
Curcumin, also known as diferuloylmethane, is the main polyphenolic substance present in the rhizomes of Curcuma longa L. This plant showed many beneficial effects and has been used since ancient times for both food and pharmaceutical purposes. Due to its pleiotropic functions, [...] Read more.
Curcumin, also known as diferuloylmethane, is the main polyphenolic substance present in the rhizomes of Curcuma longa L. This plant showed many beneficial effects and has been used since ancient times for both food and pharmaceutical purposes. Due to its pleiotropic functions, curcumin consumption in the human diet has become very common thanks also to the fact that this natural compound is considered quite safe as it does not have serious side effects. Its functions as an anti-inflammatory, anti-oxidant, neuroprotective, immunomodulatory, anti-toxicant, anti-apoptotic, and anti-diabetic compound are already known and widely demonstrated. There are numerous studies concerning its effects on various human pathologies including cancer, diabetes and arthritis while the studies on curcumin during pregnancy have been performed only in animal models. Data concerning the role of curcumin as anti-inflammatory compound suggest a possible use of curcumin in managing pregnancy complications such as Preeclampsia (PE), Gestational Diabetes Mellitus (GDM), Fetal Growth Restriction (FGR), PreTerm Birth (PTB), and exposure to toxic agents and pathogens. The aim of this review is to present data to support the possible use of curcumin in clinical trials on human gestation complications. Full article
(This article belongs to the Special Issue Lipophilic Derivative as Antioxidants)
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Open AccessArticle
Antioxidative Effects of Curcumin on the Hepatotoxicity Induced by Ochratoxin A in Rats
Antioxidants 2021, 10(1), 125; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010125 - 17 Jan 2021
Cited by 1 | Viewed by 547
Abstract
Ochratoxin A (OTA) is a powerful mycotoxin found in various foods and feedstuff, responsible for subchronic and chronic toxicity, such as nephrotoxicity, hepatotoxicity, teratogenicity, and immunotoxicity to both humans and several animal species. The severity of the liver damage caused depends on both [...] Read more.
Ochratoxin A (OTA) is a powerful mycotoxin found in various foods and feedstuff, responsible for subchronic and chronic toxicity, such as nephrotoxicity, hepatotoxicity, teratogenicity, and immunotoxicity to both humans and several animal species. The severity of the liver damage caused depends on both dose and duration of exposure. Several studies have suggested that oxidative stress might contribute to increasing the hepatotoxicity of OTA, and several antioxidants, including curcumin (CURC), have been tested to counteract the toxic hepatic action of OTA in various classes of animals. Therefore, the present study was designed to evaluate the protective effect of CURC, a bioactive compound with different therapeutic properties on hepatic injuries caused by OTA in rat animal models. CURC effects were examined in Sprague Dawley rats treated with CURC (100 mg/kg), alone or in combination with OTA (0.5 mg/kg), by gavage daily for 14 days. At the end of the experiment, rats treated with OTA showed alterations in biochemical parameters and oxidative stress in the liver. CURC dosing significantly attenuated oxidative stress and lipid peroxidation versus the OTA group. Furthermore, liver histological tests showed that CURC reduced the multifocal lymphoplasmacellular hepatitis, the periportal fibrosis, and the necrosis observed in the OTA group. This study provides evidence that CURC can preserve OTA-induced oxidative damage in the liver of rats. Full article
(This article belongs to the Special Issue Antioxidants in Veterinary Medicine)
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Open AccessReview
The Neuromelanin Paradox and Its Dual Role in Oxidative Stress and Neurodegeneration
Antioxidants 2021, 10(1), 124; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010124 - 16 Jan 2021
Viewed by 380
Abstract
Aging is associated with an increasing dysfunction of key brain homeostasis mechanisms and represents the main risk factor across most neurodegenerative disorders. However, the degree of dysregulation and the affectation of specific pathways set apart normal aging from neurodegenerative disorders. In particular, the [...] Read more.
Aging is associated with an increasing dysfunction of key brain homeostasis mechanisms and represents the main risk factor across most neurodegenerative disorders. However, the degree of dysregulation and the affectation of specific pathways set apart normal aging from neurodegenerative disorders. In particular, the neuronal metabolism of catecholaminergic neurotransmitters appears to be a specifically sensitive pathway that is affected in different neurodegenerations. In humans, catecholaminergic neurons are characterized by an age-related accumulation of neuromelanin (NM), rendering the soma of the neurons black. This intracellular NM appears to serve as a very efficient quencher for toxic molecules. However, when a neuron degenerates, NM is released together with its load (many undegraded cellular components, transition metals, lipids, xenobiotics) contributing to initiate and worsen an eventual immune response, exacerbating the oxidative stress, ultimately leading to the neurodegenerative process. This review focuses on the analysis of the role of NM in normal aging and neurodegeneration related to its capabilities as an antioxidant and scavenging of harmful molecules, versus its involvement in oxidative stress and aberrant immune response, depending on NM saturation state and its extracellular release. Full article
(This article belongs to the Special Issue Lipid Peroxidation in Neurodegeneration)
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Open AccessReview
Modulation of Autophagy in Cancer Cells by Dietary Polyphenols
Antioxidants 2021, 10(1), 123; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010123 - 16 Jan 2021
Viewed by 544
Abstract
The role of autophagy is to degrade damaged or unnecessary cellular structures. Both in vivo and in vitro studies suggest a dual role of autophagy in cancer—it may promote the development of neoplasms, but it may also play a tumor protective function. The [...] Read more.
The role of autophagy is to degrade damaged or unnecessary cellular structures. Both in vivo and in vitro studies suggest a dual role of autophagy in cancer—it may promote the development of neoplasms, but it may also play a tumor protective function. The mechanism of autophagy depends on the genetic context, tumor stage and type, tumor microenvironment, or clinical therapy used. Autophagy also plays an important role in cell death as well as in the induction of chemoresistance of cancer cells. The following review describes the extensive autophagic cell death in relation to dietary polyphenols and cancer disease. The review documents increasing use of polyphenolic compounds in cancer prevention, or as agents supporting oncological treatment. Polyphenols are organic chemicals that exhibit antioxidant, anti-inflammatory, anti-angiogenic, and immunomodulating properties, and can also initiate the process of apoptosis. In addition, polyphenols reduce oxidative stress and protect against reactive oxygen species. This review presents in vitro and in vivo studies in animal models with the use of polyphenolic compounds such as epigallocatechin-3-gallate (EGCG), oleuropein, punicalgin, apigenin, resveratrol, pterostilbene, or curcumin and their importance in the modulation of autophagy-induced death of cancer cells. Full article
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Open AccessArticle
Novel Antioxidant, Deethylated Ethoxyquin, Protects against Carbon Tetrachloride Induced Hepatotoxicity in Rats by Inhibiting NLRP3 Inflammasome Activation and Apoptosis
Antioxidants 2021, 10(1), 122; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010122 - 15 Jan 2021
Viewed by 482
Abstract
Inflammation and an increase in antioxidant responses mediated by oxidative stress play an important role in the pathogenesis of acute liver injury (ALI). We utilized in silico prediction of biological activity spectra for substances (PASS) analysis to estimate the potential biological activity profile [...] Read more.
Inflammation and an increase in antioxidant responses mediated by oxidative stress play an important role in the pathogenesis of acute liver injury (ALI). We utilized in silico prediction of biological activity spectra for substances (PASS) analysis to estimate the potential biological activity profile of deethylated ethoxyquin (DEQ) and hypothesized that DEQ exhibits antioxidant and anti-inflammatory effects in a rat model of carbon tetrachloride (CCl4)-induced ALI. Our results demonstrate that DEQ improved liver function which was indicated by the reduction of histopathological liver changes. Treatment with DEQ reduced CCl4-induced elevation of gene expression, and the activity of antioxidant enzymes (AEs), as well as the expression of transcription factors Nfe2l2 and Nfkb2. Furthermore, DEQ treatment inhibited apoptosis, downregulated gene expression of pro-inflammatory cytokines (Tnf and Il6), cyclooxygenase 2 (Ptgs2), decreased glutathione (GSH) level and myeloperoxidase (MPO) activity in rats with ALI. Notably, DEQ treatment led to an inhibition of CCl4-induced NLRP3-inflammasome activation which was indicated by the reduced protein expression of IL-1β, caspase-1, and NLRP3 in the liver. Our data suggest that DEQ has a hepatoprotective effect mediated by redox-homeostasis regulation, NLRP3 inflammasome, and apoptosis inhibition, which makes that compound a promising candidate for future clinical studies. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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Open AccessArticle
Mitochondrial Metabolism as Target of the Neuroprotective Role of Erythropoietin in Parkinson’s Disease
Antioxidants 2021, 10(1), 121; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010121 - 15 Jan 2021
Viewed by 473
Abstract
Existing therapies for Parkinson’s disease (PD) are only symptomatic. As erythropoietin (EPO) is emerging for its benefits in neurodegenerative diseases, here, we test the protective effect driven by EPO in in vitro (SH-SY5Y cells challenged by MPP+) and in vivo (C57BL/6J [...] Read more.
Existing therapies for Parkinson’s disease (PD) are only symptomatic. As erythropoietin (EPO) is emerging for its benefits in neurodegenerative diseases, here, we test the protective effect driven by EPO in in vitro (SH-SY5Y cells challenged by MPP+) and in vivo (C57BL/6J mice administered with MPTP) PD models. EPO restores cell viability in both protective and restorative layouts, enhancing the dopaminergic recovery. Specifically, EPO rescues the PD-induced damage to mitochondria, as shown by transmission electron microscopy, Mitotracker assay and PINK1 expression. Moreover, EPO promotes a rescue of mitochondrial respiration while markedly enhancing the glycolytic rate, as shown by the augmented extracellular acidification rate, contributing to elevated ATP levels in MPP+-challenged cells. In PD mice, EPO intrastriatal infusion markedly improves the outcome of behavioral tests. This is associated with the rescue of dopaminergic markers and decreased neuroinflammation. This study demonstrates cellular and functional recovery following EPO treatment, likely mediated by the 37 Kda isoform of the EPO-receptor. We report for the first time, that EPO-neuroprotection is exerted through restoring ATP levels by accelerating the glycolytic rate. In conclusion, the redox imbalance and neuroinflammation associated with PD may be successfully treated by EPO. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegenerative Disease)
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Open AccessArticle
Propagation of Mitochondria-Derived Reactive Oxygen Species within the Dipodascus magnusii Cells
Antioxidants 2021, 10(1), 120; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010120 - 15 Jan 2021
Viewed by 392
Abstract
Mitochondria are considered to be the main source of reactive oxygen species (ROS) in the cell. It was shown that in cardiac myocytes exposed to excessive oxidative stress, ROS-induced ROS release is triggered. However, cardiac myocytes have a network of densely packed organelles [...] Read more.
Mitochondria are considered to be the main source of reactive oxygen species (ROS) in the cell. It was shown that in cardiac myocytes exposed to excessive oxidative stress, ROS-induced ROS release is triggered. However, cardiac myocytes have a network of densely packed organelles that do not move, which is not typical for the majority of eukaryotic cells. The purpose of this study was to trace the spatiotemporal development (propagation) of prooxidant-induced oxidative stress and its interplay with mitochondrial dynamics. We used Dipodascus magnusii yeast cells as a model, as they have advantages over other models, including a uniquely large size, mitochondria that are easy to visualize and freely moving, an ability to vigorously grow on well-defined low-cost substrates, and high responsibility. It was shown that prooxidant-induced oxidative stress was initiated in mitochondria, far preceding the appearance of generalized oxidative stress in the whole cell. For yeasts, these findings were obtained for the first time. Preincubation of yeast cells with SkQ1, a mitochondria-addressed antioxidant, substantially diminished production of mitochondrial ROS, while only slightly alleviating the generalized oxidative stress. This was expected, but had not yet been shown. Importantly, mitochondrial fragmentation was found to be primarily induced by mitochondrial ROS preceding the generalized oxidative stress development. Full article
(This article belongs to the Special Issue Mitochondrial Reactive Oxygen Species)
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Open AccessArticle
Antitussive, Antioxidant, and Anti-Inflammatory Effects of a Walnut (Juglans regia L.) Septum Extract Rich in Bioactive Compounds
Antioxidants 2021, 10(1), 119; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010119 - 15 Jan 2021
Viewed by 551
Abstract
The antitussive, antioxidant, and anti-inflammatory effects of a walnut (Juglans regia L.) septum extract (WSE), rich in bioactive compounds were investigated using the citric acid aerosol-induced cough experimental model in rodents. Wistar male rats were treated orally for three days with distilled [...] Read more.
The antitussive, antioxidant, and anti-inflammatory effects of a walnut (Juglans regia L.) septum extract (WSE), rich in bioactive compounds were investigated using the citric acid aerosol-induced cough experimental model in rodents. Wistar male rats were treated orally for three days with distilled water (control), codeine (reference), and WSE in graded doses. On the third day, all rats were exposed to citric acid aerosols, the number of coughs being recorded. Each animal was sacrificed after exposure, and blood and lung tissue samples were collected for histopathological analysis and the assessment of oxidative stress and inflammatory biomarkers. The results of the experiment showed a significant antitussive effect of WSE, superior to codeine. This activity could be due to cellular protective effect and anti-inflammatory effect via the stimulation of the antioxidant enzyme system and the decrease of IL-6 and CXC-R1 concentration in the lung tissue of WSE-treated animals. The antioxidant and anti-inflammatory effects of WSE were confirmed by biochemical assays and histopathological analysis. This is the first scientific study reporting the antitussive effect of walnut septum, a new potential source of non-opioid antitussive drug candidates, and a valuable bioactive by-product that could be used in the treatment of respiratory diseases. Full article
(This article belongs to the Special Issue The Potential of Dietary Antioxidants)
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Open AccessArticle
Extra Virgin Olive Oil Phenolic Extract on Human Hepatic HepG2 and Intestinal Caco-2 Cells: Assessment of the Antioxidant Activity and Intestinal Trans-Epithelial Transport
Antioxidants 2021, 10(1), 118; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010118 - 15 Jan 2021
Viewed by 572
Abstract
In the framework of research aimed at promoting the nutraceutical properties of the phenolic extract (BUO) obtained from an extra virgin olive oil of the Frantoio cultivar cultivated in Tuscany (Italy), with a high total phenols content, this study provides a comprehensive characterization [...] Read more.
In the framework of research aimed at promoting the nutraceutical properties of the phenolic extract (BUO) obtained from an extra virgin olive oil of the Frantoio cultivar cultivated in Tuscany (Italy), with a high total phenols content, this study provides a comprehensive characterization of its antioxidant properties, both in vitro by Trolox equivalent antioxidant capacity, oxygen radical absorbance capacity, ferric reducing antioxidant power, and 2,2-diphenyl-1-picrylhydrazyl assays, and at the cellular level in human hepatic HepG2 and human intestinal Caco-2 cells. Notably, in both cell systems, after H2O2 induced oxidative stress, the BUO extract reduced reactive oxygen species, lipid peroxidation, and NO overproduction via modulation of inducible nitric oxide synthase protein levels. In parallel, the intestinal transport of the different phenolic components of the BUO phytocomplex was assayed on differentiated Caco-2 cells, a well-established model of mature enterocytes. The novelty of our study lies in having investigated the antioxidant effects of a complex pool of phenolic compounds in an extra virgin olive oil (EVOO) extract, using either in vitro assays or liver and intestinal cell models, rather than the effects of single phenols, such as hydroxytyrosol or oleuropein. Finally, the selective trans-epithelial transport of some oleuropein derivatives was observed for the first time in differentiated Caco-2 cells. Full article
(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)
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Open AccessArticle
Effect-Directed Profiling of Powdered Tea Extracts for Catechins, Theaflavins, Flavonols and Caffeine
Antioxidants 2021, 10(1), 117; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010117 - 15 Jan 2021
Cited by 1 | Viewed by 418
Abstract
The antioxidative activity of Camelia sinensis tea and especially powdered tea extracts on the market, among others used as added value in functional foods, can considerably vary due to not only natural variance, but also adulteration and falsification. Thus, an effect-directed profiling was [...] Read more.
The antioxidative activity of Camelia sinensis tea and especially powdered tea extracts on the market, among others used as added value in functional foods, can considerably vary due to not only natural variance, but also adulteration and falsification. Thus, an effect-directed profiling was developed to prove the functional effects or health-promoting claims. It took 3–12 min per sample, depending on the assay incubation time, for 21 separations in parallel. Used as a fast product quality control, it can detect known and unknown bioactive compounds. Twenty tea extracts and a reference mixture of 11-bioactive compounds were investigated in parallel under the same chromatographic conditions by a newly developed reversed phase high-performance thin-layer chromatographic method. In eight planar on-surface assays, effect-directed tea profiles were revealed. Catechins and theaflavins turned out to be not only highly active, but also multi-potent compounds, able to act in a broad range of metabolic pathways. The flavan-3-ols acted as radical scavengers (DPPH assay), antibacterials against Gram-positive Bacillus subtilis bacteria, and inhibitors of tyrosinase, α-glucosidase, β-glucosidase, and acetylcholinesterase. Further effects against Gram-negative Aliivibrio fischeri bacteria and β-glucuronidase were assigned to other components in the powdered tea extracts. According to their specifications, the activity responses of the powdered tea extracts were higher than in mere leaf extracts of green, white and black tea. The multi-imaging and effect-directed profiling was not only able to identify known functional food ingredients, but also to detect unknown bioactive compounds (including bioactive contaminants, residues or adulterations). Full article
(This article belongs to the Special Issue Dietary Antioxidants for Modulating the Aging Processes)
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Open AccessArticle
Effects of Fruit and Vegetable-Based Nutraceutical on Cognitive Function in a Healthy Population: Placebo-Controlled, Double-Blind, and Randomized Clinical Trial
Antioxidants 2021, 10(1), 116; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010116 - 15 Jan 2021
Viewed by 353
Abstract
There is scientific evidence of the positive effect of polyphenols from plant foods on cognition, but not enough is known about the synergistic effect when multiple polyphenols are consumed and even less in a healthy non-elderly population. The aim of the present study [...] Read more.
There is scientific evidence of the positive effect of polyphenols from plant foods on cognition, but not enough is known about the synergistic effect when multiple polyphenols are consumed and even less in a healthy non-elderly population. The aim of the present study is to investigate the possible effects of improvements in cognitive function in healthy people as a preparation based on micronized fruit and vegetables consumed. One hundred and eight subjects were selected, stratified by sex in the control intervention group (n = 53) and placebo (n = 55). Volunteers completed the study after two 16-week periods of consumption with a 4-week wash period between each phase. At the beginning and the end of each phase, volunteers performed the Stroop, TESEN, and RIST tests for the measurement of different cognitive function patterns. The results revealed statistically significant differences in all the variables of the tests carried out, especially compared with the placebo. Specially, the results obtained in the Stroop and TESEN test, in addition to the processing speed even with semantic interferences, were markedly better after the treatment with the product under study. Moreover, the consumption of the product under study clearly improves short-term memory, verbal and non-verbal, according to the results obtained in the RIST test. The results showed an improvement in executive function in terms of short-term memory, working memory, selective and sustained attention, and speed of processing. Full article
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Open AccessArticle
Phenolic Profiles, Antioxidant Activity and Phenotypic Characterization of Lonicera caerulea L. Berries, Cultivated in Lithuania
Antioxidants 2021, 10(1), 115; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010115 - 15 Jan 2021
Viewed by 390
Abstract
Lonicera caerulea L. is an early fruit-bearing plant that originates from harsh environments. Raw materials contain a body of different phenolic origin compounds that determine the multidirectional antioxidant and pharmacological activities. The aim of this study was to comprehensively evaluate the phenolic composition, [...] Read more.
Lonicera caerulea L. is an early fruit-bearing plant that originates from harsh environments. Raw materials contain a body of different phenolic origin compounds that determine the multidirectional antioxidant and pharmacological activities. The aim of this study was to comprehensively evaluate the phenolic composition, antioxidant capacities, vegetative, pomological, and sensory properties and their interrelations of selected L. caerulea cultivars, namely ‘Amphora’, ‘Wojtek’, ‘Iga’, ’Leningradskij Velikan’, ‘Nimfa’, ‘Indigo Gem’, ‘Tundra’, ‘Tola’, and fruit powders. Combined chromatographic systems were applied for the qualitative and quantitative profiling of 23 constituents belonging to the classes of anthocyanins, flavonols, flavones, proanthocyanidins, and phenolic acids. The determined markers of phytochemical profiles were cyanidin-3-glucoside, rutin, chlorogenic, and 3,5-dicaffeoylquinic acid. Anthocyanins and the predominant compound, cyanidin-3-glucoside, were the determinants of antioxidant activity. Cultivars ‘Amphora’, ‘Indigo Gem’, and ‘Tundra’ contained the greatest total amounts of identified phenolic compounds. Phenotypic characterization revealed the superiority of cultivars ‘Wojtek’ and ’Tundra’ compared to other cultivars, although ’Wojtek’ had low phenolic content and antioxidant activity and ’Tundra’ got lower sensory evaluation scores. Coupling the results of phenotypic and phytochemical characterization, cultivar ‘Tundra’ could be suitable for commercial plantations. Full article
(This article belongs to the Special Issue Phenolics as Antioxidant Agents)
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Open AccessArticle
Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers
Antioxidants 2021, 10(1), 114; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010114 - 15 Jan 2021
Viewed by 408
Abstract
Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in [...] Read more.
Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9% for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus. Full article
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Open AccessArticle
Astaxanthin-, β-Carotene-, and Resveratrol-Rich Foods Support Resistance Training-Induced Adaptation
Antioxidants 2021, 10(1), 113; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010113 - 14 Jan 2021
Viewed by 632
Abstract
Resistance training adaptively increases the muscle strength associated with protein anabolism. Previously, we showed that the combined intake of astaxanthin, β-carotene, and resveratrol can accelerate protein anabolism in the skeletal muscle of mice. The purpose of this study was to investigate the effect [...] Read more.
Resistance training adaptively increases the muscle strength associated with protein anabolism. Previously, we showed that the combined intake of astaxanthin, β-carotene, and resveratrol can accelerate protein anabolism in the skeletal muscle of mice. The purpose of this study was to investigate the effect of anabolic nutrient-rich foods on muscle adaptation induced by resistance training. Twenty-six healthy men were divided into control and intervention groups. All participants underwent a resistance training program twice a week for 10 weeks. Astaxanthin-, β-carotene-, and resveratrol-rich foods were provided to the intervention group. Body composition, nutrient intake, maximal voluntary contraction of leg extension, oxygen consumption, and serum carbonylated protein level were measured before and after training. The skeletal muscle mass was higher after training than before training in both groups (p < 0.05). Maximal voluntary contraction was increased after training in the intervention group (p < 0.05), but not significantly increased in the control group. Resting oxygen consumption was higher after training in the intervention group only (p < 0.05). As an oxidative stress marker, serum carbonylated protein level tended to be lower immediately after exercise than before exercise in the intervention group only (p = 0.056). Intake of astaxanthin-, β-carotene-, and resveratrol-rich foods supported resistance training-induced strength and metabolic adaptations. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Exercise Training and Sports)
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Open AccessArticle
Antioxidant Effects of Turmeric Leaf Extract against Hydrogen Peroxide-Induced Oxidative Stress In Vitro in Vero Cells and In Vivo in Zebrafish
Antioxidants 2021, 10(1), 112; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010112 - 14 Jan 2021
Viewed by 390
Abstract
Oxidative stress, caused by the excessive production of reactive oxygen species (ROS), results in cellular damage. Therefore, functional materials with antioxidant properties are necessary to maintain redox balance. Turmeric leaves (Curcuma longa L. leaves; TL) are known to have antioxidant properties, including [...] Read more.
Oxidative stress, caused by the excessive production of reactive oxygen species (ROS), results in cellular damage. Therefore, functional materials with antioxidant properties are necessary to maintain redox balance. Turmeric leaves (Curcuma longa L. leaves; TL) are known to have antioxidant properties, including 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2′-Azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS), and Hydrogen peroxide (H2O2) radical scavenging activity in several studies. The antioxidant effects of TL come from distinct bioactive compounds, such as curcumin, total phenolic compounds, and flavonoids. Therefore, in this study, the antioxidant effects of a water extract of TL (TLE) against H2O2 treatment were assessed in vitro Vero cells and in vivo zebrafish models. The intracellular ROS generation and the proportion of sub-G1 phase cells were evaluated in H2O2- or/and TLE-treated Vero cells to measure the antioxidant activity of TLE. TLE showed outstanding intracellular ROS scavenging activity and significantly decreased the proportion of cells in the sub-G1 phase in a dose-dependent manner. Furthermore, cell death, ROS generation, and lipid peroxidation in the H2O2-treated zebrafish model were attenuated as a consequence of TLE treatment. Collectively, the results from this study suggested that TLE may be an alternative material to relieve ROS generation through its antioxidant properties or a suitable material for the application in a functional food industry. Full article
(This article belongs to the Special Issue Antioxidant and Biological Properties of Plant Extracts)
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Open AccessArticle
Qualitative Differences in Protection of PTP1B Activity by the Reductive Trx1 or TRP14 Enzyme Systems upon Oxidative Challenges with Polysulfides or H2O2 Together with Bicarbonate
Antioxidants 2021, 10(1), 111; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010111 - 14 Jan 2021
Viewed by 316
Abstract
Protein tyrosine phosphatases (PTPs) can be regulated by several redox-dependent mechanisms and control growth factor-activated receptor tyrosine kinase phosphorylation cascades. Reversible oxidation of PTPs is counteracted by reductive enzymes, including thioredoxin (Trx) and Trx-related protein of 14 kDa (TRP14), keeping PTPs in their [...] Read more.
Protein tyrosine phosphatases (PTPs) can be regulated by several redox-dependent mechanisms and control growth factor-activated receptor tyrosine kinase phosphorylation cascades. Reversible oxidation of PTPs is counteracted by reductive enzymes, including thioredoxin (Trx) and Trx-related protein of 14 kDa (TRP14), keeping PTPs in their reduced active states. Different modes of oxidative inactivation of PTPs concomitant with assessment of activating reduction have been little studied in direct comparative analyses. Determining PTP1B activities, we here compared the potency of inactivation by bicarbonate-assisted oxidation using H2O2 with that of polysulfide-mediated inactivation. Inactivation of pure PTP1B was about three times more efficient with polysulfides as compared to the combination of bicarbonate and H2O2. Bicarbonate alone had no effect on PTP1B, neither with nor without a combination with polysulfides, thus strengthening the notion that bicarbonate-assisted H2O2-mediated inactivation of PTP1B involves formation of peroxymonocarbonate. Furthermore, PTP1B was potently protected from polysulfide-mediated inactivation by either TRP14 or Trx1, in contrast to the inactivation by bicarbonate and H2O2. Comparing reductive activation of polysulfide-inactivated PTP1B with that of bicarbonate- and H2O2-treated enzyme, we found Trx1 to be more potent in reactivation than TRP14. Altogether we conclude that inactivation of PTP1B by polysulfides displays striking qualitative differences compared to that by H2O2 together with bicarbonate, also with regard to maintenance of PTP1B activity by either Trx1 or TRP14. Full article
(This article belongs to the Special Issue Cellular Redox Homeostasis)
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Open AccessArticle
Potential Antioxidant Properties of Enzymatic Hydrolysates from Stichopus japonicus against Hydrogen Peroxide-Induced Oxidative Stress
Antioxidants 2021, 10(1), 110; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010110 - 14 Jan 2021
Viewed by 486
Abstract
A comprehensive antioxidant evaluation was performed on enzymatic hydrolysates of Stichopusjaponicus (S. japonicus) using Vero cells and zebrafish models for in vitro and in vivo studies, respectively. S. japonicus was hydrolyzed with food-grade enzymes (alcalase, α-chymotrypsin, flavourzyme, kojizyme, neutrase, papain, [...] Read more.
A comprehensive antioxidant evaluation was performed on enzymatic hydrolysates of Stichopusjaponicus (S. japonicus) using Vero cells and zebrafish models for in vitro and in vivo studies, respectively. S. japonicus was hydrolyzed with food-grade enzymes (alcalase, α-chymotrypsin, flavourzyme, kojizyme, neutrase, papain, pepsin, protamex, and trypsin), and the free radical scavenging activities were screened via electron spin resonance (ESR) spectroscopy. According to the results, the enzymatic hydrolysates contained high protein and relatively low polysaccharide and sulfate contents. Among these hydrolysates, the α-chymotrypsin assisted hydrolysate from S. japonicus (α-chy) showed high yield and protein content, and strong hydroxyl radical scavenging activity. Therefore, α-chy was chosen for further purification. The α-chy was fractionated by ultrafiltration into three ultrafiltration (UF) fractions based on their molecular weight: >10 kDa (α-chy-I), 5–10 kDa (α-chy-II), and <5 kDa (α-chy-III), and we evaluated their antioxidant properties in H2O2 exposed Vero cells. The α-chy and its UF fractions significantly decreased the intracellular reactive oxygen species (ROS) generation and increased cell viability in H2O2 exposed Vero cells. Among them, α-chy-III effectively declined the intracellular ROS levels and increased cell viability and exhibited protection against H2O2 induced apoptotic damage. Furthermore, α-chy-III remarkably attenuated the cell death, intracellular ROS and lipid peroxidation in H2O2 exposed zebrafish embryos. Altogether, our findings demonstrated that α-chy and its α-chy-III from S. japonicus possess strong antioxidant activities that could be utilized as a bioactive ingredient for functional food industries. Full article
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Open AccessArticle
Investigations into the Role of Metabolism in the Inflammatory Response of BV2 Microglial Cells
Antioxidants 2021, 10(1), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010109 - 14 Jan 2021
Viewed by 395
Abstract
Although the hallmarks of Alzheimer’s disease (AD) are amyloid beta plaques and neurofibrillary tangles, there is growing evidence that neuroinflammation, mitochondrial dysfunction and oxidative stress play important roles in disease development and progression. A major risk factor for the development of AD is [...] Read more.
Although the hallmarks of Alzheimer’s disease (AD) are amyloid beta plaques and neurofibrillary tangles, there is growing evidence that neuroinflammation, mitochondrial dysfunction and oxidative stress play important roles in disease development and progression. A major risk factor for the development of AD is diabetes, which is also characterized by oxidative stress and mitochondrial dysfunction along with chronic, low-grade inflammation. Increasing evidence indicates that in immune cells, the induction of a pro-inflammatory phenotype is associated with a shift from oxidative phosphorylation (OXPHOS) to glycolysis. However, whether hyperglycemia also contributes to this shift is not clear. Several different approaches including culturing BV2 microglial cells in different carbon sources, using enzyme inhibitors and knocking down key pathway elements were used in conjunction with bacterial lipopolysaccharide (LPS) activation to address this question. The results indicate that while high glucose favors NO production, pro-inflammatory cytokine production is highest in the presence of carbon sources that drive OXPHOS. In addition, among the carbon sources that drive OXPHOS, glutamine is a very potent inducer of IL6 production. This effect is dampened in the presence of glucose. Together, these results may provide new prospects for the therapeutic manipulation of neuroinflammation in the context of diabetes and AD. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in the Nervous System)
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