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Antioxidants, Volume 9, Issue 12 (December 2020) – 143 articles

Cover Story (view full-size image): The present review deals with reactive oxygen and nitrogen species, as they have emerged over the past centuries. It describes their discovery in biological systems, their metabolic fate, their role in host defense, their pathogenic potential, and their physiological role in redox regulation and signaling. The article ends with a critical discussion of the inflationary use of poorly defined terms such as ROS, NOS, antioxidants, and stress. View this paper
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Article
Effect of Cooking Methods on the Antioxidant Capacity of Plant Foods Submitted to In Vitro Digestion–Fermentation
Antioxidants 2020, 9(12), 1312; https://doi.org/10.3390/antiox9121312 - 21 Dec 2020
Cited by 2 | Viewed by 1103
Abstract
The antioxidant capacity of foods is essential to complement the body’s own endogenous antioxidant systems. The main antioxidant foods in the regular diet are those of plant origin. Although every kind of food has a different antioxidant capacity, thermal processing or cooking methods [...] Read more.
The antioxidant capacity of foods is essential to complement the body’s own endogenous antioxidant systems. The main antioxidant foods in the regular diet are those of plant origin. Although every kind of food has a different antioxidant capacity, thermal processing or cooking methods also play a role. In this work, the antioxidant capacity of 42 foods of vegetable origin was evaluated after in vitro digestion and fermentation. All foods were studied both raw and after different thermal processing methods, such as boiling, grilling roasting, frying, toasting and brewing. The cooking methods had an impact on the antioxidant capacity of the digested and fermented fractions, allowing the release and transformation of antioxidant compounds. In general, the fermented fraction accounted for up to 80–98% of the total antioxidant capacity. The most antioxidant foods were cocoa and legumes, which contributed to 20% of the daily antioxidant capacity intake. Finally, it was found that the antioxidant capacity of the studied foods was much higher than those reported by other authors since digestion–fermentation pretreatment allows for a higher extraction of antioxidant compounds and their transformation by the gut microbiota. Full article
(This article belongs to the Special Issue Impact of Processing on Antioxidant Rich Foods)
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Review
(Ascorb)ing Pb Neurotoxicity in the Developing Brain
Antioxidants 2020, 9(12), 1311; https://doi.org/10.3390/antiox9121311 - 21 Dec 2020
Cited by 1 | Viewed by 785
Abstract
Lead (Pb) neurotoxicity is a major concern, particularly in children. Developmental exposure to Pb can alter neurodevelopmental trajectory and has permanent neuropathological consequences, including an increased vulnerability to further stressors. Ascorbic acid is among most researched antioxidant nutrients and has a special role [...] Read more.
Lead (Pb) neurotoxicity is a major concern, particularly in children. Developmental exposure to Pb can alter neurodevelopmental trajectory and has permanent neuropathological consequences, including an increased vulnerability to further stressors. Ascorbic acid is among most researched antioxidant nutrients and has a special role in maintaining redox homeostasis in physiological and physio-pathological brain states. Furthermore, because of its capacity to chelate metal ions, ascorbic acid may particularly serve as a potent therapeutic agent in Pb poisoning. The present review first discusses the major consequences of Pb exposure in children and then proceeds to present evidence from human and animal studies for ascorbic acid as an efficient ameliorative supplemental nutrient in Pb poisoning, with a particular focus on developmental Pb neurotoxicity. In doing so, it is hoped that there is a revitalization for further research on understanding the brain functions of this essential, safe, and readily available vitamin in physiological states, as well to justify and establish it as an effective neuroprotective and modulatory factor in the pathologies of the nervous system, including developmental neuropathologies. Full article
(This article belongs to the Special Issue Role of Natural Antioxidants on Neuroprotection and Neuroinflammation)
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Review
L-Carnitine in Drosophila: A Review
Antioxidants 2020, 9(12), 1310; https://doi.org/10.3390/antiox9121310 - 21 Dec 2020
Cited by 1 | Viewed by 886
Abstract
L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial β-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance [...] Read more.
L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial β-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance of cellular energy homeostasis. L-carnitine also plays an essential role in the control of cerebral functions, and the aberrant regulation of genes involved in carnitine biosynthesis and mitochondrial carnitine transport in Drosophila models has been linked to neurodegeneration. Drosophila models of neurodegenerative diseases provide a powerful platform to both unravel the molecular pathways that contribute to neurodegeneration and identify potential therapeutic targets. Drosophila can biosynthesize L-carnitine, and its carnitine transport system is similar to the human transport system; moreover, evidence from a defective Drosophila mutant for one of the carnitine shuttle genes supports the hypothesis of the occurrence of β-oxidation in glial cells. Hence, Drosophila models could advance the understanding of the links between L-carnitine and the development of neurodegenerative disorders. This review summarizes the current knowledge on L-carnitine in Drosophila and discusses the role of the L-carnitine pathway in fly models of neurodegeneration. Full article
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Review
Antioxidant, Antimicrobial and Antiviral Properties of Herbal Materials
Antioxidants 2020, 9(12), 1309; https://doi.org/10.3390/antiox9121309 - 21 Dec 2020
Cited by 9 | Viewed by 1893
Abstract
Recently, increasing public concern about hygiene has been driving many studies to investigate antimicrobial and antiviral agents. However, the use of any antimicrobial agents must be limited due to their possible toxic or harmful effects. In recent years, due to previous antibiotics’ lesser [...] Read more.
Recently, increasing public concern about hygiene has been driving many studies to investigate antimicrobial and antiviral agents. However, the use of any antimicrobial agents must be limited due to their possible toxic or harmful effects. In recent years, due to previous antibiotics’ lesser side effects, the use of herbal materials instead of synthetic or chemical drugs is increasing. Herbal materials are found in medicines. Herbs can be used in the form of plant extracts or as their active components. Furthermore, most of the world’s populations used herbal materials due to their strong antimicrobial properties and primary healthcare benefits. For example, herbs are an excellent material to replace nanosilver as an antibiotic and antiviral agent. The use of nanosilver involves an ROS-mediated mechanism that might lead to oxidative stress-related cancer, cytotoxicity, and heart diseases. Oxidative stress further leads to increased ROS production and also delays the cellular processes involved in wound healing. Therefore, existing antibiotic drugs can be replaced with biomaterials such as herbal medicine with high antimicrobial, antiviral, and antioxidant activity. This review paper highlights the antibacterial, antiviral, and radical scavenger (antioxidant) properties of herbal materials. Antimicrobial activity, radical scavenger ability, the potential for antimicrobial, antiviral, and anticancer agents, and efficacy in eliminating bacteria and viruses and scavenging free radicals in herbal materials are discussed in this review. The presented herbal antimicrobial agents in this review include clove, portulaca, tribulus, eryngium, cinnamon, turmeric, ginger, thyme, pennyroyal, mint, fennel, chamomile, burdock, eucalyptus, primrose, lemon balm, mallow, and garlic, which are all summarized. Full article
(This article belongs to the Special Issue Antioxidants and Biomaterials in Health and Nutrition)
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Article
Whole-Body Cryostimulation Improves Inflammatory Endothelium Parameters and Decreases Oxidative Stress in Healthy Subjects
Antioxidants 2020, 9(12), 1308; https://doi.org/10.3390/antiox9121308 - 21 Dec 2020
Cited by 3 | Viewed by 670
Abstract
Background: The purpose of this study was to estimate the effect of whole-body cryostimulation (WBC) and subsequent kinesiotherapy on inflammatory endothelium and oxidative stress parameters in healthy subjects. Methods: The effects of ten WBC procedures lasting 3 min per day and followed by [...] Read more.
Background: The purpose of this study was to estimate the effect of whole-body cryostimulation (WBC) and subsequent kinesiotherapy on inflammatory endothelium and oxidative stress parameters in healthy subjects. Methods: The effects of ten WBC procedures lasting 3 min per day and followed by a 60-min session of kinesiotherapy on oxidative stress and inflammatory endothelium parameters in healthy subjects (WBC group n = 32) were analyzed. The WBC group was compared to a kinesiotherapy only (KT; n = 16) group. The following parameters were estimated one day before the start, and one day after the completion of the studies: oxidative stress parameters (the total antioxidant capacity of plasma (FRAP), paraoxonase-1 activity (PON-1), and total oxidative status (TOS)) and inflammatory endothelium parameters (myeloperoxidase activity (MPO), serum amyloid A (SAA), and sCD40L levels). Results: A significant decrease of PON-1 and MPO activities and TOS, SAA, and sCD40L levels as well as a significant FRAP increase were observed in the WBC group after the treatment. In addition, the SAA levels and PON-1 activity decreased significantly after the treatment in both groups, but the observed decrease of these parameters in the WBC group was higher in comparison to the KT group. Conclusion: WBC procedures have a beneficial impact on inflammatory endothelium and oxidative stress parameters in healthy subjects, therefore they may be used as a wellness method. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Health and Diseases)
Article
Age-Dependent Vulnerability to Oxidative Stress of Postnatal Rat Pyramidal Motor Cortex Neurons
Antioxidants 2020, 9(12), 1307; https://doi.org/10.3390/antiox9121307 - 19 Dec 2020
Viewed by 917
Abstract
Oxidative stress is one of the main proposed mechanisms involved in neuronal degeneration. To evaluate the consequences of oxidative stress on motor cortex pyramidal neurons during postnatal development, rats were classified into three groups: Newborn (P2–P7); infantile (P11–P15); and young adult (P20–P40). Oxidative [...] Read more.
Oxidative stress is one of the main proposed mechanisms involved in neuronal degeneration. To evaluate the consequences of oxidative stress on motor cortex pyramidal neurons during postnatal development, rats were classified into three groups: Newborn (P2–P7); infantile (P11–P15); and young adult (P20–P40). Oxidative stress was induced by 10 µM of cumene hydroperoxide (CH) application. In newborn rats, using the whole cell patch-clamp technique in brain slices, no significant modifications in membrane excitability were found. In infantile rats, the input resistance increased and rheobase decreased due to the blockage of GABAergic tonic conductance. Lipid peroxidation induced by CH resulted in a noticeable increase in protein-bound 4-hidroxynonenal in homogenates in only infantile and young adult rat slices. Interestingly, homogenates of newborn rat brain slices showed the highest capacity to respond to oxidative stress by dramatically increasing their glutathione and free thiol content. This increase correlated with a time-dependent increase in the glutathione reductase activity, suggesting a greater buffering capacity of newborn rats to resist oxidative stress. Furthermore, pre-treatment of the slices with glutathione monoethyl ester acted as a neuroprotector in pyramidal neurons of infantile rats. We conclude that during maturation, the vulnerability to oxidative stress in rat motor neurons increases with age. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in the Nervous System)
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Article
Fermented Soy-Derived Bioactive Peptides Selected by a Molecular Docking Approach Show Antioxidant Properties Involving the Keap1/Nrf2 Pathway
Antioxidants 2020, 9(12), 1306; https://doi.org/10.3390/antiox9121306 - 19 Dec 2020
Cited by 2 | Viewed by 864
Abstract
Bioactive peptides are a group of molecules with health beneficial properties, deriving from food matrices. They are protein fragments consisting of 2–20 amino acids that can be released by microbial fermentation, food processing and gastrointestinal digestion. Once hydrolyzed from their native proteins, they [...] Read more.
Bioactive peptides are a group of molecules with health beneficial properties, deriving from food matrices. They are protein fragments consisting of 2–20 amino acids that can be released by microbial fermentation, food processing and gastrointestinal digestion. Once hydrolyzed from their native proteins, they can have different functions including antioxidant activity, which is important for cell protection by oxidant agents. In this work, fermented soy products were digested in vitro in order to improve the release of bioactive peptides. These were extracted, purified and analyzed in vitro and in a cellular model to assess their antioxidant activity. Peptide sequences were identified by LC-MS/MS analysis and a molecular docking approach was used to predict their ability to interact with Keap1, one of the key proteins of the Keap1/Nrf2 pathway, the major system involved in redox regulation. Peptides showing a high score of interaction were selected and tested for their antioxidant properties in a cellular environment using the Caco-2 cell line and examined for their capability to defend cells against oxidative stress. Our results indicate that several of the selected peptides were indeed able to activate the Keap1/Nrf2 pathway with the consequent overexpression of antioxidant and phase II enzymes. Full article
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Article
Evaluation of Redox Profiles of the Serum and Aqueous Humor in Patients with Primary Open-Angle Glaucoma and Exfoliation Glaucoma
Antioxidants 2020, 9(12), 1305; https://doi.org/10.3390/antiox9121305 - 19 Dec 2020
Viewed by 527
Abstract
Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous [...] Read more.
Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous humor (AH) and blood samples among eyes with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and non-glaucomatous controls to evaluate the relationship among systemic redox status, intraocular oxidative stress, and clinical backgrounds. AH and blood samples were obtained from 45 eyes of 45 Japanese subjects (15 POAG, 15 EXG, and 15 control eyes). The serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. The activities of cytosolic and mitochondrial forms of the superoxide dismutase (SOD) isoforms, i.e., SOD1 and SOD2, respectively, in AH and serum were measured using a multiplex bead immunoassay. In AH, SOD1 in subjects with EXG and SOD2 in those with POAG and EXG were significantly higher than in control eyes. In serum, compared to control subjects, BAP in subjects with POAG and EXG was significantly lower; SOD1 in those with EXG and SOD2 in those with POAG and EXG were significantly higher. dROM and SH did not differ significantly among the groups. The BAP values were correlated negatively with the SOD1 concentrations in AH and serum, SOD2 in the AH, intraocular pressure, and number of antiglaucoma medications. In conclusion, lower systemic antioxidant capacity accompanies up-regulation of higher local antioxidant enzymes, suggesting increased oxidative stress in eyes with OAG, especially in EXG. Determination of the systemic BAP values may help predict the redox status in AH. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Health and Diseases)
Review
Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target
Antioxidants 2020, 9(12), 1304; https://doi.org/10.3390/antiox9121304 - 18 Dec 2020
Viewed by 1016
Abstract
Peripheral artery disease (PAD) is caused by atherosclerosis in the lower extremities, which leads to a spectrum of life-altering symptomatology, including claudication, ischemic rest pain, and gangrene requiring limb amputation. Current treatments for PAD are focused primarily on re-establishing blood flow to the [...] Read more.
Peripheral artery disease (PAD) is caused by atherosclerosis in the lower extremities, which leads to a spectrum of life-altering symptomatology, including claudication, ischemic rest pain, and gangrene requiring limb amputation. Current treatments for PAD are focused primarily on re-establishing blood flow to the ischemic tissue, implying that blood flow is the decisive factor that determines whether or not the tissue survives. Unfortunately, failure rates of endovascular and revascularization procedures remain unacceptably high and numerous cell- and gene-based vascular therapies have failed to demonstrate efficacy in clinical trials. The low success of vascular-focused therapies implies that non-vascular tissues, such as skeletal muscle and oxidative stress, may substantially contribute to PAD pathobiology. Clues toward the importance of skeletal muscle in PAD pathobiology stem from clinical observations that muscle function is a strong predictor of mortality. Mitochondrial impairments in muscle have been documented in PAD patients, although its potential role in clinical pathology is incompletely understood. In this review, we discuss the underlying mechanisms causing mitochondrial dysfunction in ischemic skeletal muscle, including causal evidence in rodent studies, and highlight emerging mitochondrial-targeted therapies that have potential to improve PAD outcomes. Particularly, we will analyze literature data on reactive oxygen species production and potential counteracting endogenous and exogenous antioxidants. Full article
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Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis
Antioxidants 2020, 9(12), 1303; https://doi.org/10.3390/antiox9121303 - 18 Dec 2020
Cited by 3 | Viewed by 1174
Abstract
Emerging evidence indicates that the dysregulation of cellular redox homeostasis and chronic inflammatory processes are implicated in the pathogenesis of kidney and brain disorders. In this light, endogenous dipeptide carnosine (β-alanyl-L-histidine) and hydrogen sulfide (H2S) exert cytoprotective actions through the modulation [...] Read more.
Emerging evidence indicates that the dysregulation of cellular redox homeostasis and chronic inflammatory processes are implicated in the pathogenesis of kidney and brain disorders. In this light, endogenous dipeptide carnosine (β-alanyl-L-histidine) and hydrogen sulfide (H2S) exert cytoprotective actions through the modulation of redox-dependent resilience pathways during oxidative stress and inflammation. Several recent studies have elucidated a functional crosstalk occurring between kidney and the brain. The pathophysiological link of this crosstalk is represented by oxidative stress and inflammatory processes which contribute to the high prevalence of neuropsychiatric disorders, cognitive impairment, and dementia during the natural history of chronic kidney disease. Herein, we provide an overview of the main pathophysiological mechanisms related to high levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and neurotoxins, which play a critical role in the kidney–brain crosstalk. The present paper also explores the respective role of H2S and carnosine in the modulation of oxidative stress and inflammation in the kidney–brain axis. It suggests that these activities are likely mediated, at least in part, via hormetic processes, involving Nrf2 (Nuclear factor-like 2), Hsp 70 (heat shock protein 70), SIRT-1 (Sirtuin-1), Trx (Thioredoxin), and the glutathione system. Metabolic interactions at the kidney and brain axis level operate in controlling and reducing oxidant-induced inflammatory damage and therefore, can be a promising potential therapeutic target to reduce the severity of renal and brain injuries in humans. Full article
(This article belongs to the Special Issue Dietary Antioxidants for Modulating the Aging Processes)
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Article
Use of Parabens (Methyl and Butyl) during the Gestation Period: Mitochondrial Bioenergetics of the Testes and Antioxidant Capacity Alterations in Testes and Other Vital Organs of the F1 Generation
Antioxidants 2020, 9(12), 1302; https://doi.org/10.3390/antiox9121302 - 18 Dec 2020
Cited by 1 | Viewed by 670
Abstract
Since the mid-1920s, parabens have been widely used as antimicrobial preservatives in processed foods and beverages, pharmaceuticals, and cosmetic products. Paraben use continues to generate considerable controversy, both in the general population and in the scientific community itself. The primary purpose of our [...] Read more.
Since the mid-1920s, parabens have been widely used as antimicrobial preservatives in processed foods and beverages, pharmaceuticals, and cosmetic products. Paraben use continues to generate considerable controversy, both in the general population and in the scientific community itself. The primary purpose of our study was to determine whether parabens (methyl and butyl at concentrations of 100 and 200 mg/kg body weight by subcutaneous injection) during pregnancy of adult female Wistar rats can have an impact on the F1 generation. As far as we know, we are the first to demonstrate that using parabens during pregnancy has negative repercussions on the mitochondrial bioenergetics and antioxidant activity of testicular germ cells in the F1 generation. Our study showed that there was a 48.7 and 59.8% decrease in the respiratory control index with 100 and 200 mg/kg of butylparaben, respectively. Cytochrome c oxidase activity was significantly inhibited (45 and 51%) in both groups. In addition, 200 mg/kg butylparaben promoted a marked decrease in citrate synthase activity, indicating that mitochondrial content decreased in the germ cells, especially spermatocytes and spermatids. Mitochondrial ROS production increased in groups exposed to parabens in a concentration-dependent manner, especially the butyl one (102 and 130%). The groups exposed to butylparaben showed an increase in superoxide dismutase (SOD) and catalase (CAT) activities, while glutathione reductase (GR) and glutathione S-transferase (GST) decreased. With methylparaben, only differences in SOD and GR were observed; for the latter, this only occurred with the highest concentration. The glutathione (GSH)/glutathione disulfide (GSSG) ratio did not undergo any significant change. However, there was a considerable increase in hydroperoxide content in animals exposed to butylparaben, with 100 and 200 mg/kg resulting in 98.6 and 188% increase, respectively. Furthermore, several other organs also showed alterations in antioxidant capacity due to paraben use. In summary, our study demonstrates that paraben use during pregnancy will cause severe changes in the mitochondrial bioenergetics and antioxidant capacity of testicular germ cells and the antioxidant capacity of several other F1 generation organs. Full article
(This article belongs to the Special Issue Mitochondria Biology in Reproductive Function)
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Article
Tyrosinase Inhibitory Activity of Soybeans Fermented with Bacillus subtilis Capable of Producing a Phenolic Glycoside, Arbutin
Antioxidants 2020, 9(12), 1301; https://doi.org/10.3390/antiox9121301 - 18 Dec 2020
Cited by 2 | Viewed by 730
Abstract
The production of arbutin, an effective tyrosinase inhibitor as well as an outstanding antioxidant, by 691 Bacillus strains isolated from soybean-based foods was tested to enhance the tyrosinase inhibitory activity of soybeans via fermentation with the strains. Among the strains tested, the 5 [...] Read more.
The production of arbutin, an effective tyrosinase inhibitor as well as an outstanding antioxidant, by 691 Bacillus strains isolated from soybean-based foods was tested to enhance the tyrosinase inhibitory activity of soybeans via fermentation with the strains. Among the strains tested, the 5 strains capable of significantly producing arbutin were identified as B. subtilis via 16S rRNA sequencing. When soybeans were fermented with each of the selected strains, the arbutin content was highest on day 1 of fermentation and decreased thereafter. However, the tyrosinase inhibitory activity of the fermented soybeans continuously increased as fermentation progressed, whereas the activity of non-inoculated soybeans was consistently low. The results indicate that arbutin enhances the tyrosinase inhibitory activity of soybeans in the early period of fermentation, while other substances besides arbutin contribute to the activity in the later period. Consequently, soybeans fermented with arbutin-producing B. subtilis strains could be considered as a natural source of cosmeceuticals and nutricosmetics used in skin lightening and may be of interest in the food industry because they contain well-known and powerful antioxidants such as arbutin and other substances. Full article
(This article belongs to the Special Issue Antioxidants and Bioactive Compounds in Fermented Foods)
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Article
The Effect of Glutathione Peroxidase-1 Knockout on Anticancer Drug Sensitivities and Reactive Oxygen Species in Haploid HAP-1 Cells
Antioxidants 2020, 9(12), 1300; https://doi.org/10.3390/antiox9121300 - 18 Dec 2020
Cited by 1 | Viewed by 666
Abstract
The role of glutathione peroxidases (GPx) in cancer and their influence on tumor prognosis and the development of anticancer drug resistance has been extensively and controversially discussed. The aim of this study was to evaluate the influence of GPx1 expression on anticancer drug [...] Read more.
The role of glutathione peroxidases (GPx) in cancer and their influence on tumor prognosis and the development of anticancer drug resistance has been extensively and controversially discussed. The aim of this study was to evaluate the influence of GPx1 expression on anticancer drug cytotoxicity. For this purpose, a GPx1 knockout of the near-haploid human cancer cell line HAP-1 was generated and compared to the native cell line with regards to morphology, growth and metabolic rates, and oxidative stress defenses. Furthermore, the IC50 values of two peroxides and 16 widely used anticancer drugs were determined in both cell lines. Here we report that the knockout of GPx1 in HAP-1 cells has no significant effect on cell size, viability, growth and metabolic rates. Significant increases in the cytotoxic potency of hydrogen peroxide and tert-butylhydroperoxide, the anticancer drugs cisplatin and carboplatin as well as the alkylating agents lomustine and temozolomide were found. While a concentration dependent increases in intracellular reactive oxygen species (ROS) levels were observed for both HAP-1 cell lines treated with either cisplatin, lomustine or temozolamide, no significant enhancement in ROS levels was observed in the GPx1 knockout compared to the native cell line except at the highest concentration of temozolamide. On the other hand, a ca. 50% decrease in glutathione levels was noted in the GPx1 knockout relative to the native line, suggesting that factors other than ROS levels alone play a role in the increased cytotoxic activity of these drugs in the GPx1 knockout cells. Full article
(This article belongs to the Special Issue Antioxidants and Cancer)
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Article
Melatonin Reduces NLRP3 Inflammasome Activation by Increasing α7 nAChR-Mediated Autophagic Flux
Antioxidants 2020, 9(12), 1299; https://doi.org/10.3390/antiox9121299 - 18 Dec 2020
Cited by 3 | Viewed by 928
Abstract
Microglia controls the immune system response in the brain. Specifically, the activation and dysregulation of the NLRP3 inflammasome is responsible for the initiation of the inflammatory process through IL-1β and IL-18 release. In this work, we have focused on studying the effect of [...] Read more.
Microglia controls the immune system response in the brain. Specifically, the activation and dysregulation of the NLRP3 inflammasome is responsible for the initiation of the inflammatory process through IL-1β and IL-18 release. In this work, we have focused on studying the effect of melatonin on the regulation of the NLRP3 inflammasome through α7 nicotinic receptor (nAChR) and its relationship with autophagy. For this purpose, we have used pharmacological and genetic approaches in lipopolysaccharide (LPS)-induced inflammation models in both in vitro and in vivo models. In the BV2 cell line, LPS inhibited autophagy, which increased NLRP3 protein levels. However, melatonin promoted an increase in the autophagic flux. Treatment of glial cultures from wild-type (WT) mice with LPS followed by extracellular adenosine triphosphate (ATP) produced the release of IL-1β, which was reversed by melatonin pretreatment. In cultures from α7 nAChR knock-out (KO) mice, melatonin did not reduce IL-1β release. Furthermore, melatonin decreased the expression of inflammasome components and reactive oxygen species (ROS) induced by LPS; co-incubation of melatonin with α-bungarotoxin (α-bgt) or luzindole abolished the anti-inflammatory and antioxidant effects. In vivo, melatonin reverted LPS-induced cognitive decline, reduced NLRP3 levels and promoted autophagic flux in the hippocampi of WT mice, whereas in α7 nAChR KO mice melatonin effect was not observed. These results suggest that melatonin may modulate the complex interplay between α7 nAChR and autophagy signaling. Full article
(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Inflammatory Actions)
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Article
Effect of Castor and Cashew Nut Shell Oils, Selenium and Vitamin E as Antioxidants on the Health and Meat Stability of Lambs Fed a High-Concentrate Diet
Antioxidants 2020, 9(12), 1298; https://doi.org/10.3390/antiox9121298 - 18 Dec 2020
Cited by 2 | Viewed by 877
Abstract
Functional oils are known for their compounds with antioxidant, antimicrobial and anti-inflammatory properties, and are used in ruminant nutrition as alternatives to chemicals in order to improve performance. This study aimed to compare the influence of castor and cashew nut shell oils with [...] Read more.
Functional oils are known for their compounds with antioxidant, antimicrobial and anti-inflammatory properties, and are used in ruminant nutrition as alternatives to chemicals in order to improve performance. This study aimed to compare the influence of castor and cashew nut shell oils with pure organic selenium (hydroxy-selenomethionine) plus vitamin E, which are known and well-stablished antioxidants, on the performance traits, shelf life and microbial quality of the meat, physiological functions and oxidative stress control of lambs. Thirty-two Dorper x Santa Ines lambs (initial bodyweight of 22.42 ± 3.9 kg and 60 days of age) were submitted to a diet consisting of Cynodon dactylon hay (6%) and concentrate (94%). The animals were divided into four treatments: control, without additives; functional oils (FO), 0.50 g/kg DM of castor and cashew nut shell oils; hydroxy-selenomethionine and vitamin E (SeE), 0.50 mg/kg of organic selenium and 100 IU/kg DM of vitamin E; FO plus SeE, at the same doses as the other groups. Blood samples were collected after 1, 30 and 53 days on feed. After 54 days, the lambs were slaughtered and rumen health, carcass and meat traits, shelf life, and microbiological quality were evaluated. There were no differences in performance or carcass traits. A higher muscle and serum Se concentration (p < 0.0001), lower lipid peroxidation in meat during display (p < 0.0001), and a lower count of psychrotrophic microorganisms on day 5 were observed in the SeE and FO plus SeE groups. The treatments reduced the counts of Enterobacteriaceae, and Staphylococcus spp. FO animals showed higher GSH-Px activity on day 30, while the peroxidase activity was higher in FO plus SeE animals (p = 0.035). SeE and FO plus SeE animals had lower serum ALT and AST levels. Functional oils improved the microbiological quality of meat. Hydroxy-selenomethionine and vitamin E prevented oxidative stress, lipid peroxidation, and microbial spoilage. Full article
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Article
A Comparative Study on Phenolic Content, Antioxidant Activity and Anti-Inflammatory Capacity of Aqueous and Ethanolic Extracts of Sorghum in Lipopolysaccharide-Induced RAW 264.7 Macrophages
Antioxidants 2020, 9(12), 1297; https://doi.org/10.3390/antiox9121297 - 18 Dec 2020
Cited by 2 | Viewed by 1185
Abstract
Sorghum is an important cereal with diverse phenolic compounds that have potential health promoting benefits. The current study comparatively characterized the phenolic contents of two novel black-seeded sorghum lines (SC84 and PI570481) using different extraction systems (water, ethanol and their acidified counterparts) and [...] Read more.
Sorghum is an important cereal with diverse phenolic compounds that have potential health promoting benefits. The current study comparatively characterized the phenolic contents of two novel black-seeded sorghum lines (SC84 and PI570481) using different extraction systems (water, ethanol and their acidified counterparts) and evaluated their antioxidant and anti-inflammatory activities. Phenolic compositions were determined by spectrophotometric assays and HPLC analysis. Antioxidant activities were assessed by radical scavenging effects on nitric oxide (NO) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, and the oxygen radical absorbance capacity (ORAC). Anti-inflammatory capacity was estimated by measuring levels of pro-inflammatory markers produced by lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Results showed that effects of solvent types and HCl on extraction efficiency differed among phenolic compounds and sorghum samples. Tannins were the most dominant polyphenols in the studied extracts (11.11–136.11 mg epicatechin equivalent/g sorghum). Sorghum extracts exerted more potent scavenging activity on DPPH than NO radicals. In LPS-activated RAW 264.7 cells, sorghum extracts dose-dependently inhibited the production of NO, interleukin-6 (IL-6), and intracellular reactive oxygen species (ROS), with ethanolic extracts showing greater anti-inflammatory activity. Positive correlations were noted between tannin content and DPPH radical scavenging activity, and anti-inflammatory capacity. These results suggest the potential role of tannin-rich sorghum extracts against inflammation and associated diseases. Full article
(This article belongs to the Special Issue Anti-inflammatory and Antioxidant Properties of Plant Extracts)
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Carotenoids, Vitamin C, and Antioxidant Capacity in the Peel of Mandarin Fruit in Relation to the Susceptibility to Chilling Injury during Postharvest Cold Storage
Antioxidants 2020, 9(12), 1296; https://doi.org/10.3390/antiox9121296 - 17 Dec 2020
Cited by 3 | Viewed by 985
Abstract
Chilling injury (CI) is a postharvest disorder occurring in the fruit of cold-sensitive Citrus species during storage at low temperatures. This study investigated the involvement of carotenoids and vitamin C, two major antioxidants of citrus peel, and the antioxidant capacity in the CI [...] Read more.
Chilling injury (CI) is a postharvest disorder occurring in the fruit of cold-sensitive Citrus species during storage at low temperatures. This study investigated the involvement of carotenoids and vitamin C, two major antioxidants of citrus peel, and the antioxidant capacity in the CI susceptibility of mandarin fruit. To that end, the fruit of three commercial varieties, Fortune, Nova, and Nadorcott, with significant differences in CI susceptibility, were selected. By on-tree fruit bagging, carotenoids and vitamin C contents were modified, and a differential effect of each cultivar on CI was observed. Carotenoid analysis in the peel revealed a strong negative correlation between total carotenoid concentration (TCC) at harvest, and specifically of β-cryptoxanthin and violaxanthin, and CI index at the end of storage. In contrast, vitamin C content was significantly and positively correlated with CI susceptibility. The antioxidant activity assessed by the DPPH• and FRAP reflected the contribution of vitamin C to the antioxidant system, while the SOAC assay correlated positively with TTC, β-cryptoxanthin, and violaxanthin. Collectively, the antioxidant capacity of carotenoids at harvest, as efficient singlet oxygen quenchers, suggests a protective role against the development of CI in mandarin fruit, while vitamin C is not likely playing a critical role. Full article
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Article
Phenolic Profile and Bioactive Potential of Stems and Seed Kernels of Sweet Cherry Fruit
Antioxidants 2020, 9(12), 1295; https://doi.org/10.3390/antiox9121295 - 17 Dec 2020
Cited by 4 | Viewed by 1233
Abstract
Every year, large quantities of stems and pits are generated during sweet cherry processing, without any substantial use. Although stems are widely recognized by traditional medicine, detailed and feasible information about their bioactive composition or biological value is still scarce, as well as [...] Read more.
Every year, large quantities of stems and pits are generated during sweet cherry processing, without any substantial use. Although stems are widely recognized by traditional medicine, detailed and feasible information about their bioactive composition or biological value is still scarce, as well as the characterization of kernels. Therefore, we conducted a study in which bioactivity potential of extracts from stems and kernels of four sweet cherry cultivars (Early Bigi (grown under net cover (C) and without net cover (NC)), Burlat, Lapins, and Van) were examined. The assays included antioxidant (by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and β-carotene-linoleic acid bleaching assays), and antibacterial activities against important Gram negative and Gram positive bacterial human isolates. Profile and individual phenolic composition of each extract were determined by High-performance liquid chromatography (HPLC) analysis. Extracts from stems of cv. Lapins and kernels of Early Bigi NC presented high levels of total phenolics, flavonoids, ortho-diphenols and saponins. Excepting for cv. Early Bigi NC, major phenolic compounds identified in stems and kernels were sakuranetin and catechin, respectively. In cv. Early Bigi NC the most abundant compounds were ellagic acid for stems and protocatechuic acid for kernels. In all extracts, antioxidant activities showed a positive correlation with the increments in phenolic compounds. Antimicrobial activity assays showed that only stem’s extracts were capable of inhibiting the growth of Gram positive isolates. This new data is intended to provide new possibilities of valorization of these by-products and their valuable properties. Full article
(This article belongs to the Special Issue Phenolics as Antioxidant Agents)
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Article
Seasonality Modulates the Cellular Antioxidant Activity and Antiproliferative Effect of Sonoran Desert Propolis
Antioxidants 2020, 9(12), 1294; https://doi.org/10.3390/antiox9121294 - 17 Dec 2020
Viewed by 1192
Abstract
The main chemical composition and pharmacological potential of propolis from arid and semi-arid regions of the Sonoran Desert have been previously reported. Caborca propolis (CP), from an arid zone of the Sonoran Desert, has shown a polyphenolic profile that suggests a mixed plant [...] Read more.
The main chemical composition and pharmacological potential of propolis from arid and semi-arid regions of the Sonoran Desert have been previously reported. Caborca propolis (CP), from an arid zone of the Sonoran Desert, has shown a polyphenolic profile that suggests a mixed plant origin, presenting poplar-type markers, as well as a 6-methoxylated flavonoid, xanthomicrol, characteristic of Asteraceae plants. In addition, CP has shown significant antioxidant properties and antiproliferative activity on cancer cells. In this study, we analyzed the influence of collection time on the chemical constitution, antiproliferative activity and protective capacity of CP against reactive oxygen species (ROS), by using HPLC–UV–diode array detection (DAD) analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-Dimethyltetrazoliumbromide (MTT) and 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assays, as well as cellular antioxidant activity (CAA) assay on murine B-cell lymphoma M12.C3.F6 cells. HPLC–UV–DAD analyses of seasonally collected CP (one-year period) revealed quantitative differences among the most abundant CP constituents: pinocembrin, galangin, chrysin and pinobanksin-3-O-acetate. Though all seasonal samples of CP induced an antiproliferative effect in M12.C3.F6 cells, CP from autumn showed the highest inhibitory activity (IC50: 5.9 ± 0.6 µg/mL). The DPPH assay pointed out that CP collected in autumn presented the highest antioxidant potential (IC50: 58.8 ± 6.7 µg/mL), followed by winter (65.7 ± 12.2 µg/mL) and spring (67.0 ± 7.5 µg/mL); meanwhile, the summer sample showed a lesser antioxidant capacity (IC50: 98.7 ± 2.5 µg/mL). The CAA assay demonstrated that CP induced a significant protective effect against ROS production elicited by H2O2 in M12.C3.F6 cells. Pretreatment of M12.C3.F6 cells with CP from spring and autumn (25 and 50 µg/mL for 1 h) showed the highest reduction in intracellular ROS induced by H2O2 (1 and 5 mM). These results indicate that the antiproliferative effect and cellular antioxidant activity of CP are modulated by quantitative fluctuations in its polyphenolic profile due to its collection time. Full article
(This article belongs to the Special Issue Bee Products as a Source of Natural Antioxidants)
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Communication
Heme-Iron-Induced Production of 4-Hydroxynonenal in Intestinal Lumen May Have Extra-Intestinal Consequences through Protein-Adduct Formation
Antioxidants 2020, 9(12), 1293; https://doi.org/10.3390/antiox9121293 - 17 Dec 2020
Cited by 1 | Viewed by 635
Abstract
Some epidemiological studies show that heme iron consumption, in red meat, is associated to the development of several chronic diseases, including cancers and cardio-metabolic diseases. As heme iron intestinal absorption is finely regulated, we hypothesized that heme iron may act indirectly, through the [...] Read more.
Some epidemiological studies show that heme iron consumption, in red meat, is associated to the development of several chronic diseases, including cancers and cardio-metabolic diseases. As heme iron intestinal absorption is finely regulated, we hypothesized that heme iron may act indirectly, through the peroxidation of dietary lipids, in food or in the intestinal lumen during digestion. This heme-iron-induced lipid peroxidation provokes the generation of toxic lipid oxidation products that could be absorbed, such as 4-hydroxynonenal (HNE). In a first experiment, heme iron given to rats by oral gavage together with the linoleic-acid-rich safflower oil induced the formation of HNE in the intestinal lumen. The HNE major urinary metabolite was elevated in the urine of the treated rats, indicating that this compound has been absorbed. In a second experiment, we showed that stable isotope-labeled HNE given orally to rats was able to reach non-intestinal tissues as a bioactive form and to make protein-adducts in heart, liver and skeletal muscle tissues. The presence of HNE-protein adducts in those tissues suggests a putative biological role of diet-originating HNE in extra-intestinal organs. This finding could have major consequences on the onset/development of chronic diseases associated with red meat over-consumption, and more largely to peroxidation-prone food consumption. Full article
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Review
Oxidative Stress and Antioxidant Treatments in Cardiovascular Diseases
Antioxidants 2020, 9(12), 1292; https://doi.org/10.3390/antiox9121292 - 17 Dec 2020
Cited by 6 | Viewed by 851
Abstract
Oxidative stress plays a key role in many physiological and pathological conditions. The intracellular oxidative homeostasis is tightly regulated by the reactive oxygen species production and the intracellular defense mechanisms. Increased oxidative stress could alter lipid, DNA, and protein, resulting in cellular inflammation [...] Read more.
Oxidative stress plays a key role in many physiological and pathological conditions. The intracellular oxidative homeostasis is tightly regulated by the reactive oxygen species production and the intracellular defense mechanisms. Increased oxidative stress could alter lipid, DNA, and protein, resulting in cellular inflammation and programmed cell death. Evidences show that oxidative stress plays an important role in the progression of various cardiovascular diseases, such as atherosclerosis, heart failure, cardiac arrhythmia, and ischemia-reperfusion injury. There are a number of therapeutic options to treat oxidative stress-associated cardiovascular diseases. Well known antioxidants, such as nutritional supplements, as well as more novel antioxidants have been studied. In addition, novel therapeutic strategies using miRNA and nanomedicine are also being developed to treat various cardiovascular diseases. In this article, we provide a detailed description of oxidative stress. Then, we will introduce the relationship between oxidative stress and several cardiovascular diseases. Finally, we will focus on the clinical implications of oxidative stress in cardiovascular diseases. Full article
(This article belongs to the Special Issue Oxidative stress and Applied Biology)
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Article
Effect of Rosmarinic Acid and Ionizing Radiation on Glutathione in Melanoma B16F10 Cells: A Translational Opportunity
Antioxidants 2020, 9(12), 1291; https://doi.org/10.3390/antiox9121291 - 16 Dec 2020
Cited by 1 | Viewed by 593
Abstract
To explain a paradoxical radiosensitizing effect of rosmarinic acid (RA) on the melanoma B16F10 cells, we analyzed the glutathione (GSH) intracellular production on this cell (traditionally considered radioresistant) in comparison with human prostate epithelial cells (PNT2) (considered to be radiosensitive). In PNT2 cells, [...] Read more.
To explain a paradoxical radiosensitizing effect of rosmarinic acid (RA) on the melanoma B16F10 cells, we analyzed the glutathione (GSH) intracellular production on this cell (traditionally considered radioresistant) in comparison with human prostate epithelial cells (PNT2) (considered to be radiosensitive). In PNT2 cells, the administration of RA increased the total GSH content during the first 3 h (p < 0.01) as well as increased the GSH/oxidized glutathione (GSSG) ratio in all irradiated cultures during all periods studied (1h and 3h) (p < 0.001), portraying an increase in the radioprotective capacity. However, in B16F10 cells, administration of RA had no effect on the total intracellular GSH levels, decreasing the GSH/GSSG ratio (p < 0.01); in addition, it caused a significant reduction in the GSH/GSSG ratio in irradiated cells (p < 0.001), an expression of radioinduced cell damage. In B16F10 cells, the administration of RA possibly activates the metabolic pathway of eumelanin synthesis that would consume intracellular GSH, thereby reducing its possible use as a protector against oxidative stress. The administration of this type of substance during radiotherapy could potentially protect healthy cells for which RA is a powerful radioprotector, and at the same time, cause significant damage to melanoma cells for which it could act as a radiosensitive agent. Full article
(This article belongs to the Special Issue Antioxidants and Cancer)
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Article
Radical Scavenging-Linked Anti-Adipogenic Activity of Aster scaber Ethanolic Extract and Its Bioactive Compound
Antioxidants 2020, 9(12), 1290; https://doi.org/10.3390/antiox9121290 - 16 Dec 2020
Viewed by 567
Abstract
Aster scaber is a wild vegetable cultivated in Korea and is known to contain phytochemicals with various biological activities. The potential antioxidant and anti-obesity effects of A. scaber and their mechanism are yet to be reported. We evaluated the total phenolic, flavonoid, and [...] Read more.
Aster scaber is a wild vegetable cultivated in Korea and is known to contain phytochemicals with various biological activities. The potential antioxidant and anti-obesity effects of A. scaber and their mechanism are yet to be reported. We evaluated the total phenolic, flavonoid, and proanthocyanidin contents and oxygen radical absorbance capacity of A. scaber ethanolic extract (ASE), and analyzed the major phenolic compounds of ASE. Antioxidant activity was measured at the chemical level through 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power assay, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), and fluorescence recovery after photobleaching (FRAP) assay. In addition, it was measured in vitro through inhibition of Reactive oxygen species (ROS) production in 3T3-L1 adipocyte, and inhibition of lipid accumulation was also evaluated. ASE reduced the expression of enzymes involved in the production of ROS and increased the expression of antioxidant enzymes that reduce increased ROS levels. They also reduced the expression of adipogenesis transcription factors that regulate adipocyte differentiation in relation to ROS production, inhibited the expression of lipogenesis-related genes related to fat accumulation through AMP-activated protein kinase (AMPK) activity, and increased expression of lipolysis-related genes. Thus, ASE containing CGA (chlorogenic acid) inhibits ROS production in 3T3-L1 adipocytes, owing to its strong antioxidant activity, and inhibits lipid accumulation caused by oxidative stress. The extract can be used as a potential functional food material for reducing oxidative stress and obesity. Full article
(This article belongs to the Special Issue Antioxidants and Biomaterials in Health and Nutrition)
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Article
Assessment of Rosemary (Rosmarinus officinalis L.) Extract as Antioxidant in Jelly Candies Made with Fructan Fibres and Stevia
Antioxidants 2020, 9(12), 1289; https://doi.org/10.3390/antiox9121289 - 16 Dec 2020
Cited by 2 | Viewed by 1334
Abstract
Enrichment with rosemary antioxidants is proposed as a possible strategy to obtain healthier jelly candies. Two aqueous rosemary extracts (RE) containing 73.9 (RE74) and 145.6 (RE146) mg polyphenols per g fresh weight were assessed as antioxidants in jelly candies based on fructooligosaccharides, inulin [...] Read more.
Enrichment with rosemary antioxidants is proposed as a possible strategy to obtain healthier jelly candies. Two aqueous rosemary extracts (RE) containing 73.9 (RE74) and 145.6 (RE146) mg polyphenols per g fresh weight were assessed as antioxidants in jelly candies based on fructooligosaccharides, inulin and stevia. Up to 15 phenolic acids, flavonoids and diterpenes were determined in the extracts, with rosmarinic acid as the main active compound. Sensory tolerance, physical properties, rosmarinic acid recovery, polyphenol content, and antioxidant capacity were determined in jelly candies. The threshold of sensory detection was established at 0.26 g RE146/kg of raw candy, below which rosemary off-flavours were avoided without altering pH, brix, texture, CIELab colour, and consumer acceptance. Adding 0.26 g RE146 per kg increased (p < 0.001) polyphenol content from 197 to 411 µg GAE/g and the antioxidant capacity from 1.77 to 4.14 μmol Trolox/g. Rosemary polyphenols resulted in being resistant to cooking, acted as secondary antioxidants and showed good interaction with the other jelly ingredients. Aqueous extracts from rosemary distillation by-products can be incorporated at acceptable levels to jelly candy formulations leading to higher oxidative stability and an increased content of dietary polyphenols. Full article
(This article belongs to the Special Issue Plant Antioxidants for Food Safety and Quality)
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Review
The Writers, Readers, and Erasers in Redox Regulation of GAPDH
Antioxidants 2020, 9(12), 1288; https://doi.org/10.3390/antiox9121288 - 16 Dec 2020
Cited by 3 | Viewed by 1136
Abstract
Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which [...] Read more.
Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH toward different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g., sulfenylation, S-thiolation, nitrosylation, and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization, and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders. Full article
(This article belongs to the Special Issue Redox Language of the Cell)
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Article
Association of Antioxidants Use with All-Cause and Cause-Specific Mortality: A Prospective Study of the UK Biobank
Antioxidants 2020, 9(12), 1287; https://doi.org/10.3390/antiox9121287 - 16 Dec 2020
Viewed by 881
Abstract
Prospective studies and randomized controlled trials elucidating the impact of antioxidants supplementation on mortality risk are inconclusive. The present analysis determined association between regular antioxidants use and all-cause (primary objective), as well as cause-specific, mortality in 345,626 participants of the UK Biobank cohort [...] Read more.
Prospective studies and randomized controlled trials elucidating the impact of antioxidants supplementation on mortality risk are inconclusive. The present analysis determined association between regular antioxidants use and all-cause (primary objective), as well as cause-specific, mortality in 345,626 participants of the UK Biobank cohort using Cox proportional hazard models. All models were adjusted for confounders and multiple testing. Antioxidants users were defined as participants who indicated to regularly use at least one of the following: multivitamins, vitamin C, vitamin E, selenium, and zinc. Median age of antioxidants users (n = 101,159) and non-users (n = 244,467) at baseline was 57 years. During 3.9 million person-years and a median follow-up of 11.5 years, 19,491 deaths occurred. Antioxidants use was not significantly associated with all-cause, cancer, and non-cancer mortality including several cancer and non-cancer subtypes. Interestingly, mortality risk from respiratory disease was significantly 21% lower among antioxidants users as compared to non-users (hazard ratio: 0.79; 95% confidence interval: 0.67, 0.92). In conclusion, the present study findings do not support recommendations for antioxidants supplementation to prevent all-cause, cancer, or non-cancer mortality on a population level. The significant inverse association between antioxidants use and respiratory disease mortality needs further study. Full article
(This article belongs to the Special Issue Dietary Antioxidants for Modulating the Aging Processes)
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Article
Chemical Profiling, Antioxidant, Cytotoxic Activities and Molecular Docking Simulation of Carrichtera annua DC. (Cruciferae)
Antioxidants 2020, 9(12), 1286; https://doi.org/10.3390/antiox9121286 - 16 Dec 2020
Cited by 4 | Viewed by 877
Abstract
Our investigation intended to analyze the chemical composition and the antioxidant activity of Carrichtera annua and to evaluate the antiproliferative effect of C. annua crude and phenolics extracts by MTT assay on a panel of cancerous and non-cancerous breast and liver cell lines. [...] Read more.
Our investigation intended to analyze the chemical composition and the antioxidant activity of Carrichtera annua and to evaluate the antiproliferative effect of C. annua crude and phenolics extracts by MTT assay on a panel of cancerous and non-cancerous breast and liver cell lines. The total flavonoid and phenolic contents of C. annua were 47.3 ± 17.9 mg RE/g and 83.8 ± 5.3 mg respectively. C. annua extract exhibited remarkable antioxidant capacity (50.92 ± 5.64 mg GAE/g) in comparison with BHT (74.86 ± 3.92 mg GAE/g). Moreover, the extract exhibited promising reduction ability (1.17 mMol Fe+2/g) in comparison to the positive control (ascorbic acid with 2.75 ± 0.91) and it displayed some definite radical scavenging effect on DPPH (IC50 values of 211.9 ± 3.7 µg/mL). Chemical profiling of C. annua extract was achieved by LC-ESI-TOF-MS/MS analysis. Forty-nine hits mainly polyphenols were detected. Flavonoid fraction of C. annua was more active than the crude extract. It demonstrated selective cytotoxicity against the MCF-7 and HepG2 cells (IC50 = 13.04 and 19.3 µg/mL respectively), induced cell cycle arrest at pre-G1 and G2/M-phases and displayed apoptotic effect. Molecular docking studies supported our findings and revealed that kaempferol-3,7-O-bis-α-L-rhamnoside and kaempferol-3-rutinoside were the most active inhibitors of Bcl-2. Therefore, C. annua herb seems to be a promising candidate to further advance anticancer research. In extrapolation, the intake of C. annua phenolics might be adventitious for alleviating breast and liver malignancies and tumoral proliferation in humans. Full article
(This article belongs to the Special Issue Antioxidant and Biological Properties of Plant Extracts)
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Article
Spontaneous Formation of Melanin from Dopamine in the Presence of Iron
Antioxidants 2020, 9(12), 1285; https://doi.org/10.3390/antiox9121285 - 16 Dec 2020
Viewed by 932
Abstract
Parkinson’s disease is associated with degeneration of neuromelanin (NM)-containing substantia nigra dopamine (DA) neurons and subsequent decreases in striatal DA transmission. Dopamine spontaneously forms a melanin through a process called melanogenesis. The present study examines conditions that promote/prevent DA melanogenesis. The kinetics, intermediates, [...] Read more.
Parkinson’s disease is associated with degeneration of neuromelanin (NM)-containing substantia nigra dopamine (DA) neurons and subsequent decreases in striatal DA transmission. Dopamine spontaneously forms a melanin through a process called melanogenesis. The present study examines conditions that promote/prevent DA melanogenesis. The kinetics, intermediates, and products of DA conversion to melanin in vitro, and DA melanogenesis under varying levels of Fe3+, pro-oxidants, and antioxidants were examined. The rate of melanogenesis for DA was substantially greater than related catecholamines norepinephrine and epinephrine and their precursor amino acids tyrosine and l-Dopa as measured by UV-IR spectrophotometry. Dopamine melanogenesis was concentration dependent on the pro-oxidant species and Fe3+. Melanogenesis was enhanced by the pro-oxidant hydrogen peroxide (EC50 = 500 μM) and decreased by the antioxidants ascorbate (IC50 = 10 μM) and glutathione (GSH; IC50 = 5 μM). Spectrophotometric results were corroborated by tuning a fast-scan cyclic voltammetry system to monitor DA melanogenesis. Evoked DA release in striatal brain slices resulted in NM formation that was prevented by GSH. These findings suggest that DA melanogenesis occurs spontaneously under physiologically-relevant conditions of oxidative stress and that NM may act as a marker of past exposure to oxidative stress. Full article
(This article belongs to the Collection Feature Paper in ROS, RNS, RSS)
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Article
Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration
Antioxidants 2020, 9(12), 1284; https://doi.org/10.3390/antiox9121284 - 16 Dec 2020
Cited by 1 | Viewed by 625
Abstract
In clinical practice, inflammatory pain is an important, unresolved health problem, despite the utilization of non-steroidal anti-inflammatory drugs (NSAIDs). In the last decade, different studies have proven that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in the development and [...] Read more.
In clinical practice, inflammatory pain is an important, unresolved health problem, despite the utilization of non-steroidal anti-inflammatory drugs (NSAIDs). In the last decade, different studies have proven that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in the development and maintenance of inflammatory pain and hyperalgesia via the post-translation modification of key proteins, such as manganese superoxide dismutase (MnSOD). It is well-known that inducible cyclooxygenase 2 (COX-2) plays a crucial role at the beginning of the inflammatory response by converting arachidonic acid into proinflammatory prostaglandin PGE2 and then producing other proinflammatory chemokines and cytokines. Here, we investigated the impact of oxidative stress on COX-2 and prostaglandin (PG) pathways in paw exudates, and we studied how this mechanism can be reversed by using antioxidants during hyperalgesia in a well-characterized model of inflammatory pain in rats. Our results reveal that during the inflammatory state, induced by intraplantar administration of carrageenan, the increase of PGE2 levels released in the paw exudates were associated with COX-2 nitration. Moreover, we showed that the inhibition of ROS with Mn (III) tetrakis (4-benzoic acid) porphyrin(MnTBAP) antioxidant prevented COX-2 nitration, restored the PGE2 levels, and blocked the development of thermal hyperalgesia. Full article
(This article belongs to the Special Issue Antioxidants and Chronic Inflammation)
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Review
N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature
Antioxidants 2020, 9(12), 1283; https://doi.org/10.3390/antiox9121283 - 16 Dec 2020
Cited by 8 | Viewed by 1317
Abstract
Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease [...] Read more.
Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential. Full article
(This article belongs to the Special Issue Oxidative Stress in Obesity)
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