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Antioxidants, Volume 9, Issue 11 (November 2020) – 141 articles

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Open AccessArticle
Profiling of Low-Molecular-Weight Carbonyls and Protein Modifications in Flavored Milk
Antioxidants 2020, 9(11), 1169; https://doi.org/10.3390/antiox9111169 - 23 Nov 2020
Viewed by 235
Abstract
Thermal treatments of dairy products favor oxidations, Maillard reactions, and the formation of sugar or lipid oxidation products. Additives including flavorings might enhance these reactions or even induce further reactions. Here we aimed to characterize protein modifications in four flavored milk drinks using [...] Read more.
Thermal treatments of dairy products favor oxidations, Maillard reactions, and the formation of sugar or lipid oxidation products. Additives including flavorings might enhance these reactions or even induce further reactions. Here we aimed to characterize protein modifications in four flavored milk drinks using samples along the production chain—raw milk, pasteurization, mixing with flavorings, heat treatment, and the commercial product. Therefore, milk samples were analyzed using a bottom up proteomics approach and a combination of data-independent (MSE) and data-dependent acquisition methods (DDA). Twenty-one small carbonylated lipids were identified by shotgun lipidomics triggering 13 protein modifications. Additionally, two Amadori products, 12 advanced glycation end products (AGEs), and 12 oxidation-related modifications were targeted at the protein level. The most common modifications were lactosylation, formylation, and carboxymethylation. The numbers and distribution of modification sites present in raw milk remained stable after pasteurization and mixing with flavorings, while the final heat treatment significantly increased lactosylation and hexosylation in qualitative and quantitative terms. The processing steps did not significantly affect the numbers of AGE-modified, oxidized/carbonylated, and lipid-carbonylated sites in proteins. Full article
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Open AccessArticle
Raspberry Ketones Attenuate Cyclophosphamide-Induced Pulmonary Toxicity in Mice through Inhibition of Oxidative Stress and NF-ΚB Pathway
Antioxidants 2020, 9(11), 1168; https://doi.org/10.3390/antiox9111168 - 23 Nov 2020
Viewed by 224
Abstract
Cyclophosphamide (CP) was found to have a potential toxic effect on lung tissues. Raspberry ketones (RKs) are natural antioxidant chemicals isolated from red raspberries (Rubus ideaus). They are commonly used for weight loss and obesity. The current study aimed to evaluate the possible [...] Read more.
Cyclophosphamide (CP) was found to have a potential toxic effect on lung tissues. Raspberry ketones (RKs) are natural antioxidant chemicals isolated from red raspberries (Rubus ideaus). They are commonly used for weight loss and obesity. The current study aimed to evaluate the possible protective effects of RKs against lung toxicity induced by CP. Mice were allocated into six groups: (1) control group; (2) CP group: received a single intraperitoneal dose of CP (150 mg/kg, i.p.); and (3–6) mice were pre-treated orally with different doses of RKs (25, 50, 100, and 200 mg/kg) for 14 consecutive days, respectively, before the administration of an intraperitoneal dose of CP (150 mg/kg, i.p.). Mice were then sacrificed under anesthesia, then lungs were removed for histopathological and biochemical investigations. A single dose of CP markedly altered the levels of some oxidative stress biomarkers and resulted in the fragmentation of DNA in lung homogenates. Histological examination of CP-treated mice demonstrated diffuse alveolar damage that involved apparent hyalinization of membranes, thickening of inter alveolar septa, and proliferation of type II pneumocytes. The immunohistochemical results of CP-treated mice revealed strongly positive Bax and weakly positive proliferating cell nuclear antigen (PCNA) staining reactivity of the nuclei of the lining epithelium of the bronchioles and alveoli. CP activated the cyclooxygenase-2/nuclear factor-kappa B pathway. However, pre-treatment with RKs significantly attenuated CP-evoked alterations in the previously mentioned parameters, highlighting their antioxidant, anti-inflammatory, and anti-apoptotic potential. RKs may be suggested to be a potential candidate to ameliorate CP-induced pulmonary toxicity. Full article
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Open AccessArticle
Inhibition of Osteoclast Differentiation by Carotenoid Derivatives through Inhibition of the NF-κB Pathway
Antioxidants 2020, 9(11), 1167; https://doi.org/10.3390/antiox9111167 - 23 Nov 2020
Viewed by 191
Abstract
The bone protective effects of carotenoids have been demonstrated in several studies, and the inhibition of RANKL-induced osteoclast differentiation by lycopene has also been demonstrated. We previously reported that carotenoid oxidation products are the active mediators in the activation of the transcription factor [...] Read more.
The bone protective effects of carotenoids have been demonstrated in several studies, and the inhibition of RANKL-induced osteoclast differentiation by lycopene has also been demonstrated. We previously reported that carotenoid oxidation products are the active mediators in the activation of the transcription factor Nrf2 and the inhibition of the NF-κB transcription system by carotenoids. Here, we demonstrate that lycopene oxidation products are more potent than intact lycopene in inhibiting osteoclast differentiation. We analyzed the structure–activity relationship of a series of dialdehyde carotenoid derivatives (diapocarotene-dials) in inhibiting osteoclastogenesis. We found that the degree of inhibition depends on the electron density of the carbon atom that determines the reactivity of the conjugated double bond in reactions such as Michael addition to thiol groups in proteins. Moreover, the carotenoid derivatives attenuated the NF-κB signal through inhibition of IκB phosphorylation and NF-κB translocation to the nucleus. In addition, we show a synergistic inhibition of osteoclast differentiation by combinations of an active carotenoid derivative with the polyphenols curcumin and carnosic acid with combination index (CI) values < 1. Our findings suggest that carotenoid derivatives inhibit osteoclast differentiation, partially by inhibiting the NF-κB pathway. In addition, carotenoid derivatives can synergistically inhibit osteoclast differentiation with curcumin and carnosic acid. Full article
(This article belongs to the Special Issue Antioxidants in Foods)
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Open AccessReview
The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms
Antioxidants 2020, 9(11), 1166; https://doi.org/10.3390/antiox9111166 - 23 Nov 2020
Viewed by 645
Abstract
Oxidative stress can be induced by various stimuli and altered in certain conditions, including exercise and pain. Although many studies have investigated oxidative stress in relation to either exercise or pain, the literature presents conflicting results. Therefore, this review critically discusses existing literature [...] Read more.
Oxidative stress can be induced by various stimuli and altered in certain conditions, including exercise and pain. Although many studies have investigated oxidative stress in relation to either exercise or pain, the literature presents conflicting results. Therefore, this review critically discusses existing literature about this topic, aiming to provide a clear overview of known interactions between oxidative stress, exercise, and pain in healthy people as well as in people with chronic pain, and to highlight possible confounding factors to keep in mind when reflecting on these interactions. In addition, autonomic regulation and epigenetic mechanisms are proposed as potential mechanisms of action underlying the interplay between oxidative stress, exercise, and pain. This review highlights that the relation between oxidative stress, exercise, and pain is poorly understood and not straightforward, as it is dependent on the characteristics of exercise, but also on which population is investigated. To be able to compare studies on this topic, strict guidelines should be developed to limit the effect of several confounding factors. This way, the true interplay between oxidative stress, exercise, and pain, and the underlying mechanisms of action can be revealed and validated via independent studies. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Exercise Training and Sports)
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Open AccessFeature PaperArticle
Extracellular Vesicles from SOD3-Transduced Stem Cells Exhibit Improved Immunomodulatory Abilities in the Murine Dermatitis Model
Antioxidants 2020, 9(11), 1165; https://doi.org/10.3390/antiox9111165 - 23 Nov 2020
Viewed by 192
Abstract
The immunoregulatory abilities of mesenchymal stem cells (MSCs) have been investigated in various autoimmune and allergic diseases. However, the therapeutic benefits observed in preclinical settings have not been reproducible in clinical trials. This discrepancy is due to insufficient efficacy of MSCs in harsh [...] Read more.
The immunoregulatory abilities of mesenchymal stem cells (MSCs) have been investigated in various autoimmune and allergic diseases. However, the therapeutic benefits observed in preclinical settings have not been reproducible in clinical trials. This discrepancy is due to insufficient efficacy of MSCs in harsh microenvironments, as well as batch-dependent variability in potency. Therefore, to achieve more beneficial and uniform outcomes, novel strategies are required to potentiate the therapeutic effect of MSCs. One of simple strategies to augment cellular function is genetic manipulation. Several studies showed that transduction of antioxidant enzyme into cells can increase anti-inflammatory effects. Therefore, we evaluated the immunoregulatory abilities of MSCs introduced with extracellular superoxide dismutase 3 (SOD3) in the present study. SOD3-overexpressed MSCs (SOD3-MSCs) reduced the symptoms of murine model of atopic dermatitis (AD)-like inflammation, as well as the differentiation and activation of various immune cells involved in AD progression. Interestingly, extracellular vesicles (EVs) isolated from SOD3-MSCs delivered SOD3 protein. EVs carrying SOD3 also exerted improved therapeutic efficacy, as observed in their parent cells. These results suggest that MSCs transduced with SOD3, an antioxidant enzyme, as well as EVs isolated from modified cells, might be developed as a promising cell-based therapeutics for inflammatory disorders. Full article
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Open AccessFeature PaperArticle
Polyphenolic and Methylxanthine Bioaccessibility of Cocoa Bean Shell Functional Biscuits: Metabolomics Approach and Intestinal Permeability through Caco-2 Cell Models
Antioxidants 2020, 9(11), 1164; https://doi.org/10.3390/antiox9111164 - 22 Nov 2020
Viewed by 266
Abstract
Cocoa bean shell (CBS), a by-product with considerable concentrations of bioactive compounds and proven biofunctional potential, has been demonstrated to be a suitable ingredient for high-fiber functional biscuits adapted to diabetic consumers. In this work, the in vitro bioaccessibility and intestinal absorption of [...] Read more.
Cocoa bean shell (CBS), a by-product with considerable concentrations of bioactive compounds and proven biofunctional potential, has been demonstrated to be a suitable ingredient for high-fiber functional biscuits adapted to diabetic consumers. In this work, the in vitro bioaccessibility and intestinal absorption of polyphenols and methylxanthines contained in these biscuits were evaluated, and the effect of the food matrix was studied. Biscuits containing CBS and the CBS alone underwent in vitro digestion followed by an intestinal permeability study. The results confirmed that compounds were less bioavailable in the presence of a food matrix, although the digestion contributed to their release from this matrix, increasing the concentrations available at the intestinal level and making them capable of promoting antioxidant and antidiabetic activities. After digestion, CBS biscuits were shown to possess α-glucosidase inhibition capacity comparable to that of acarbose. Moreover, the presence of the food matrix improved the stability of polyphenols throughout the digestion process. Intestinal absorption of flavan-3-ols seemed to be limited to a maximum threshold and was therefore independent of the sample, while procyanidin was not absorbed. Methylxanthine absorption was high and was boosted by the presence of the food matrix. The results confirmed the biofunctional potential of CBS-based biscuits. Full article
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Open AccessArticle
Sinapic Acid Inhibits Cardiac Hypertrophy via Activation of Mitochondrial Sirt3/SOD2 Signaling in Neonatal Rat Cardiomyocytes
Antioxidants 2020, 9(11), 1163; https://doi.org/10.3390/antiox9111163 - 21 Nov 2020
Viewed by 367
Abstract
Sinapic acid (SA) is a naturally occurring phenolic compound with antioxidant properties. It also has a wide range of pharmacological properties, such as anti-inflammatory, anticancer, and hepatoprotective properties. The present study aimed to evaluate the potential pharmacological effects of SA against hypertrophic responses [...] Read more.
Sinapic acid (SA) is a naturally occurring phenolic compound with antioxidant properties. It also has a wide range of pharmacological properties, such as anti-inflammatory, anticancer, and hepatoprotective properties. The present study aimed to evaluate the potential pharmacological effects of SA against hypertrophic responses in neonatal rat cardiomyocytes. In order to evaluate the preventive effect of SA on cardiac hypertrophy, phenylephrine (PE)-induced hypertrophic cardiomyocytes were treated with subcytotoxic concentrations of SA. SA effectively suppressed hypertrophic responses, such as cell size enlargement, sarcomeric rearrangement, and fetal gene re-expression. In addition, SA significantly inhibited the expression of mitogen-activated protein kinase (MAPK) proteins as pro-hypertrophic factors and protected the mitochondrial functions from hypertrophic stimuli. Notably, SA activated Sirt3, a mitochondrial deacetylase, and SOD2, a mitochondrial antioxidant, in hypertrophic cardiomyocytes. SA also inhibited oxidative stress in hypertrophic cardiomyocytes. However, the protective effect of SA was significantly reduced in Sirt3-silenced hypertrophic cardiomyocytes, indicating that SA exerts its beneficial effect through Sirt3/SOD signaling. In summary, this is the first study to reveal the potential pharmacological action and inhibitory mechanism of SA as an antioxidant against cardiac hypertrophy, suggesting that SA could be utilized for the treatment of cardiac hypertrophy. Full article
(This article belongs to the Special Issue Natural Antioxidant in Cardiovascular and Cerebrovascular Diseases)
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Open AccessArticle
Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice
Antioxidants 2020, 9(11), 1162; https://doi.org/10.3390/antiox9111162 - 21 Nov 2020
Viewed by 401
Abstract
The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low [...] Read more.
The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low dose: 45%; NAM high dose: 55%) in NAM-treated, apolipoprotein (Apo)E-deficient mice challenged with a Western diet for 4 weeks. NAM administration significantly increased (1.8-fold) the plasma concentration of proatherogenic ApoB-containing lipoproteins in NAM high-dose (HD)-treated mice compared with untreated mice. However, isolated ApoB-containing lipoproteins from NAM HD mice were less prone to oxidation than those of untreated mice. This result was consistent with the decreased (1.5-fold) concentration of oxidized low-density lipoproteins in this group. Immunohistochemical staining of aortas from NAM-treated mice showed significantly increased levels of IL-10 (NAM low-dose (LD): 1.3-fold; NAM HD: 1.2-fold), concomitant with a significant decrease in the relative expression of TNFα (NAM LD: −44%; NAM HD: −57%). An improved anti-inflammatory pattern was reproduced in macrophages cultured in the presence of NAM. Thus, dietary NAM supplementation in ApoE-deficient mice prevented the development of atherosclerosis and improved protection against ApoB-containing lipoprotein oxidation and aortic inflammation. Full article
(This article belongs to the Special Issue Antioxidants in the Prevention and Treatment of Chronic Diseases)
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Open AccessArticle
Oleacein Attenuates the Pathogenesis of Experimental Autoimmune Encephalomyelitis through Both Antioxidant and Anti-Inflammatory Effects
Antioxidants 2020, 9(11), 1161; https://doi.org/10.3390/antiox9111161 - 21 Nov 2020
Viewed by 439
Abstract
Oxidative stress and proinflammatory cytokines are factors affecting multiple sclerosis (MS) disease progression. Oleacein (OLE), an olive secoiridoid, possesses powerful antioxidant and anti-inflammatory activities, which suggests its potential application to treat neuroinflammatory disorders. Herein, we investigated the impact of OLE on the main [...] Read more.
Oxidative stress and proinflammatory cytokines are factors affecting multiple sclerosis (MS) disease progression. Oleacein (OLE), an olive secoiridoid, possesses powerful antioxidant and anti-inflammatory activities, which suggests its potential application to treat neuroinflammatory disorders. Herein, we investigated the impact of OLE on the main clinic-pathological features of experimental autoimmune encephalomyelitis (EAE), an animal model for MS, including paralysis, demyelination, central nervous system (CNS) inflammation/oxidative stress and blood-brain barrier (BBB) breakdown. Methods: Mice were immunized with the myelin oligodendrocyte glycoprotein peptide, MOG35-55, to induce EAE, and OLE was administrated from immunization day. Serum, optic nerve, spinal cord and cerebellum were collected to evaluate immunomodulatory activities at a systemic level, as well as within the CNS. Additionally, BV2 microglia and the retinal ganglion cell line RGC-5 were used to confirm the direct effect of OLE on CNS-resident cells. Results: We show that OLE treatment effectively reduced clinical score and histological signs typical of EAE. Histological evaluation confirmed a decrease in leukocyte infiltration, demyelination, BBB disruption and superoxide anion accumulation in CNS tissues of OLE-treated EAE mice compared to untreated ones. OLE significantly decreased expression of proinflammatory cytokines (IL-13, TNFα, GM-CSF, MCP-1 and IL-1β), while it increased the anti-inflammatory cytokine IL-10. Serum levels of anti-MOG35-55 antibodies were also lower in OLE-treated EAE mice. Further, OLE significantly diminished the presence of oxidative system parameters, while upregulated the ROS disruptor, Sestrin-3. Mechanistically, OLE prevented NLRP3 expression, phosphorylation of p65-NF-κB and reduced the synthesis of proinflammatory mediators induced by relevant inflammatory stimuli in BV2 cells. OLE did not affect viability or the phagocytic capabilities of BV2 microglia. In addition, apoptosis of RGC-5 induced by oxidative stressors was also prevented by OLE. Conclusion: Altogether, our results show that the antioxidant and anti-inflammatory OLE has neuroprotective effects in the CNS of EAE mice, pointing out this natural product as a candidate to consider for research on MS treatments. Full article
(This article belongs to the Special Issue Olive Oil Antioxidants)
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Open AccessArticle
Generation of Rat Monoclonal Antibody to Detect Hydrogen Sulfide and Polysulfides in Biological Samples
Antioxidants 2020, 9(11), 1160; https://doi.org/10.3390/antiox9111160 - 21 Nov 2020
Viewed by 210
Abstract
Hydrogen sulfide (H2S) is endogenously produced by enzymes and via reactive persulfide/polysulfide degradation; it participates in a variety of biological processes under physiological and pathological conditions. H2S levels in biological fluids, such as plasma and serum, are correlated with [...] Read more.
Hydrogen sulfide (H2S) is endogenously produced by enzymes and via reactive persulfide/polysulfide degradation; it participates in a variety of biological processes under physiological and pathological conditions. H2S levels in biological fluids, such as plasma and serum, are correlated with the severity of various diseases. Therefore, development of a simple and selective H2S measurement method would be advantageous. This study aimed to generate antibodies specifically recognizing H2S derivatives and develop a colorimetric immunoassay for measuring H2S in biological samples. We used N-ethylmaleimide (NEM) as an H2S detection agent that forms a stable bis-S-adduct (NEM-S-NEM). We also prepared bis-S-heteroadduct with 3-maleimidopropionic acid, which, in conjugation with bovine serum albumin, was to immunize Japanese white rabbits and Wistar rats to enable generation of polyclonal and monoclonal antibodies, respectively. The generated antibodies were evaluated by competitive enzyme-linked immunosorbent assay. We could obtain two stable hybridoma cell lines producing monoclonal antibodies specific for NEM-S-NEM. By immunoassay with the monoclonal antibody, the H2S level in mouse plasma was determined as 0.2 μM, which was identical to the level detected by mass spectrometry. Taken together, these monoclonal antibodies can be a useful tool for a simple and highly selective immunoassay to detect H2S in biological samples. Full article
(This article belongs to the Special Issue Delivery of Gaseous Signal Molecules)
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Open AccessArticle
Dopamine Therapy and the Regulation of Oxidative Stress and Mitochondrial DNA Copy Number in Patients with Parkinson’s Disease
Antioxidants 2020, 9(11), 1159; https://doi.org/10.3390/antiox9111159 - 20 Nov 2020
Viewed by 206
Abstract
Few studies have reported on changes to oxidative stress and mitochondrial DNA copy numbers in patients with Parkinson’s disease (PD), particularly those undergoing long-term dopamine therapy. This study measured mitochondrial copy numbers, thiobarbituric acid reactive substances (TBARS), and thiols in 725 PD patients [...] Read more.
Few studies have reported on changes to oxidative stress and mitochondrial DNA copy numbers in patients with Parkinson’s disease (PD), particularly those undergoing long-term dopamine therapy. This study measured mitochondrial copy numbers, thiobarbituric acid reactive substances (TBARS), and thiols in 725 PD patients and 744 controls. The total prescribed dopamine dose was calculated for each PD patient. A decreased mitochondrial copy number and antioxidant thiols level, but an elevated oxidative TBARS level presented in PD patients. Stratification into age subgroups revealed a consistently lower mitochondrial copy number and thiols in all PD subgroups, but increased TBARS levels compared with those of the controls. Further study found an association between lower serum TBARS and dopamine administration. There appears to be an indirect relationship with the mitochondrial copy number, where a decrease in TBARS was found to diminish the effect of pathogenetic and age-related decrease in mitochondrial copy number in PD patients. Follow-up evaluations noted more significant decreases of mitochondrial copy numbers in PD patients over time; meanwhile, dopamine administration was associated with an initial decrease of the TBARS level which attenuated with high-dose and long-term therapy. Our study provides evidence that moderate dopamine dose therapy benefits PD patients through attenuation of oxidative stress and manipulation of the mitochondrial copy number. Full article
(This article belongs to the Special Issue Lipid Peroxidation in Neurodegeneration)
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Open AccessArticle
Possible A2E Mutagenic Effects on RPE Mitochondrial DNA from Innovative RNA-Seq Bioinformatics Pipeline
Antioxidants 2020, 9(11), 1158; https://doi.org/10.3390/antiox9111158 - 20 Nov 2020
Viewed by 196
Abstract
Mitochondria are subject to continuous oxidative stress stimuli that, over time, can impair their genome and lead to several pathologies, like retinal degenerations. Our main purpose was the identification of mtDNA variants that might be induced by intense oxidative stress determined by N [...] Read more.
Mitochondria are subject to continuous oxidative stress stimuli that, over time, can impair their genome and lead to several pathologies, like retinal degenerations. Our main purpose was the identification of mtDNA variants that might be induced by intense oxidative stress determined by N-retinylidene-N-retinylethanolamine (A2E), together with molecular pathways involving the genes carrying them, possibly linked to retinal degeneration. We performed a variant analysis comparison between transcriptome profiles of human retinal pigment epithelial (RPE) cells exposed to A2E and untreated ones, hypothesizing that it might act as a mutagenic compound towards mtDNA. To optimize analysis, we proposed an integrated approach that foresaw the complementary use of the most recent algorithms applied to mtDNA data, characterized by a mixed output coming from several tools and databases. An increased number of variants emerged following treatment. Variants mainly occurred within mtDNA coding sequences, corresponding with either the polypeptide-encoding genes or the RNA. Time-dependent impairments foresaw the involvement of all oxidative phosphorylation complexes, suggesting a serious damage to adenosine triphosphate (ATP) biosynthesis, that can result in cell death. The obtained results could be incorporated into clinical diagnostic settings, as they are hypothesized to modulate the phenotypic expression of mtDNA pathogenic variants, drastically improving the field of precision molecular medicine. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Retinal Degeneration)
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Open AccessArticle
Antioxidant and Anti-Inflammatory Activities of Cytocompatible Salvia officinalis Extracts: A Comparison between Traditional and Soxhlet Extraction
Antioxidants 2020, 9(11), 1157; https://doi.org/10.3390/antiox9111157 - 20 Nov 2020
Viewed by 387
Abstract
Chronic inflammation is characterized by an overproduction of several inflammatory mediators (e.g., reactive species and interleukins -IL) that play a central role in numerous diseases. The available therapies are often associated with serious side effects and, consequently, the need for safer drugs is [...] Read more.
Chronic inflammation is characterized by an overproduction of several inflammatory mediators (e.g., reactive species and interleukins -IL) that play a central role in numerous diseases. The available therapies are often associated with serious side effects and, consequently, the need for safer drugs is of utmost importance. A plant traditionally used in the treatment of inflammatory conditions is Salvia officinalis. Therefore, conventional maceration and infusion of its leaves were performed to obtain hydroethanolic (HE-T) and aqueous extracts (AE-T), respectively. Their efficacy was compared to soxhlet extracts, namely aqueous (AE-S), hydroethanolic (HE-S), and ethanolic extracts (EE-S). Thin-layer chromatography demonstrated the presence of rosmarinic acid, carnosol, and/or carnosic acid in the different extracts. Generally, soxhlet provided extracts with higher antioxidant activities than traditional extraction. Moreover, under an inflammatory scenario, EE-S were the most effective, followed by HE-S, HE-T, AE-T, and AE-S, in the reduction of IL-6 and TNF-α production. Interestingly, the extracts presented higher or similar anti-inflammatory activity than diclofenac, salicylic acid, and celecoxib. In conclusion, the extraction method and the solvents of extraction influenced the antioxidant activity, but mainly the anti-inflammatory activity of the extracts. Therefore, this natural resource can enable the development of effective treatments for oxidative stress and inflammatory diseases. Full article
(This article belongs to the Special Issue Antioxidant and Biological Properties of Plant Extracts)
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Open AccessReview
Redox Potential of Antioxidants in Cancer Progression and Prevention
Antioxidants 2020, 9(11), 1156; https://doi.org/10.3390/antiox9111156 - 20 Nov 2020
Viewed by 215
Abstract
The benevolent and detrimental effects of antioxidants are much debated in clinical trials and cancer research. Several antioxidant enzymes and molecules are overexpressed in oxidative stress conditions that can damage cellular proteins, lipids, and DNA. Natural antioxidants remove excess free radical intermediates by [...] Read more.
The benevolent and detrimental effects of antioxidants are much debated in clinical trials and cancer research. Several antioxidant enzymes and molecules are overexpressed in oxidative stress conditions that can damage cellular proteins, lipids, and DNA. Natural antioxidants remove excess free radical intermediates by reducing hydrogen donors or quenching singlet oxygen and delaying oxidative reactions in actively growing cancer cells. These reducing agents have the potential to hinder cancer progression only when administered at the right proportions along with chemo-/radiotherapies. Antioxidants and enzymes affect signal transduction and energy metabolism pathways for the maintenance of cellular redox status. A decline in antioxidant capacity arising from genetic mutations may increase the mitochondrial flux of free radicals resulting in misfiring of cellular signalling pathways. Often, a metabolic reprogramming arising from these mutations in metabolic enzymes leads to the overproduction of so called ’oncometabolites’ in a state of ‘pseudohypoxia’. This can inactivate several of the intracellular molecules involved in epigenetic and redox regulations, thereby increasing oxidative stress giving rise to growth advantages for cancerous cells. Undeniably, these are cell-type and Reactive Oxygen Species (ROS) specific, which is manifested as changes in the enzyme activation, differences in gene expression, cellular functions as well as cell death mechanisms. Photodynamic therapy (PDT) using light-activated photosensitizing molecules that can regulate cellular redox balance in accordance with the changes in endogenous ROS production is a solution for many of these challenges in cancer therapy. Full article
(This article belongs to the Special Issue Anticancer Antioxidants)
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Open AccessArticle
The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses
Antioxidants 2020, 9(11), 1155; https://doi.org/10.3390/antiox9111155 - 20 Nov 2020
Viewed by 256
Abstract
Physical activity has an influence on a variety of processes in an athlete’s organism including the immune system. Unfortunately, there is a lack of studies regarding racehorse immune cells, especially when the horse model is compared to human exercise physiology. The aim of [...] Read more.
Physical activity has an influence on a variety of processes in an athlete’s organism including the immune system. Unfortunately, there is a lack of studies regarding racehorse immune cells, especially when the horse model is compared to human exercise physiology. The aim of the study was to determine changes in immune cell proliferation, lymphocyte populations, and monocyte functionality in trained and untrained racehorses after exercise. In this study, field data were collected. The cells from 28 racehorses (14 untrained and 14 well-trained) were collected before and after exercise (800 m at a speed of about 800 m/min) and cultured for 4 days. The expression of CD4, CD8, FoxP3, CD14, MHCII, and CD5 in PBMC, and reactive oxygen species (ROS) production, as well as cell proliferation, were evaluated by flow cytometry. In addition, IL-1β, IL-4, IL-6, IL-10, IL-17, INF-γ, and TNF-α concentrations were evaluated by ELISA. The creation of an anti-inflammatory environment in well-trained horses was confirmed. In contrast, a pro-inflammatory reaction occurred in untrained horses after training. In conclusion, an anti-inflammatory state occurs in well-trained racehorses, which is an adaptational reaction to an increased workload during training. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Exercise Training and Sports)
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Open AccessArticle
Expression of Pro-Angiogenic Markers Is Enhanced by Blue Light in Human RPE Cells
Antioxidants 2020, 9(11), 1154; https://doi.org/10.3390/antiox9111154 - 20 Nov 2020
Viewed by 229
Abstract
Inherited retinal dystrophies are characterized by photoreceptor death. Oxidative stress usually occurs, increasing vision loss, and oxidative damage is often reported in retinitis pigmentosa (RP). More than 300 genes have been reported as RP causing. In contrast, choroidal neovascularization (CNV) only occasionally develops [...] Read more.
Inherited retinal dystrophies are characterized by photoreceptor death. Oxidative stress usually occurs, increasing vision loss, and oxidative damage is often reported in retinitis pigmentosa (RP). More than 300 genes have been reported as RP causing. In contrast, choroidal neovascularization (CNV) only occasionally develops in the late stages of RP. We herein study the regulation of RP causative genes that are likely linked to CNV onset under oxidative conditions. We studied how the endogenous adduct N-retinylidene-N-retinylethanolamine (A2E) affects the expression of angiogenic markers in human retinal pigment epithelium (H-RPE) cells and a possible correlation with RP-causing genes. H-RPE cells were exposed to A2E and blue light for 3 and 6h. By transcriptome analysis, genes differentially expressed between A2E-treated cells and untreated ones were detected. The quantification of differential gene expression was performed by the Limma R package. Enrichment pathway analysis by the FunRich tool and gene prioritization by ToppGene allowed us to identify dysregulated genes involved in angiogenesis and linked to RP development. Two RP causative genes, AHR and ROM1, can be associated with an increased risk of CNV development. Genetic analysis of RP patients affected by CNV will confirm this hypothesis. Full article
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Open AccessReview
Therapeutic Potential of Heme Oxygenase-1 and Carbon Monoxide in Acute Organ Injury, Critical Illness, and Inflammatory Disorders
Antioxidants 2020, 9(11), 1153; https://doi.org/10.3390/antiox9111153 - 19 Nov 2020
Viewed by 385
Abstract
Heme oxygenase-1 (HO-1) is an inducible stress protein that catalyzes the oxidative conversion of heme to carbon monoxide (CO), iron, and biliverdin (BV), the latter of which is converted to bilirubin (BR) by biliverdin reductase. HO-1 has been implicated as a cytoprotectant in [...] Read more.
Heme oxygenase-1 (HO-1) is an inducible stress protein that catalyzes the oxidative conversion of heme to carbon monoxide (CO), iron, and biliverdin (BV), the latter of which is converted to bilirubin (BR) by biliverdin reductase. HO-1 has been implicated as a cytoprotectant in various models of acute organ injury and disease (i.e., lung, kidney, heart, liver). Thus, HO-1 may serve as a general therapeutic target in inflammatory diseases. HO-1 may function as a pleiotropic modulator of inflammatory signaling, via the removal of heme, and generation of its enzymatic degradation-products. Iron release from HO activity may exert pro-inflammatory effects unless sequestered, whereas BV/BR have well-established antioxidant properties. CO, derived from HO activity, has been identified as an endogenous mediator that can influence mitochondrial function and/or cellular signal transduction programs which culminate in the regulation of apoptosis, cellular proliferation, and inflammation. Much research has focused on the application of low concentration CO, whether administered in gaseous form by inhalation, or via the use of CO-releasing molecules (CORMs), for therapeutic benefit in disease. The development of novel CORMs for their translational potential remains an active area of investigation. Evidence has accumulated for therapeutic effects of both CO and CORMs in diseases associated with critical care, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS), mechanical ventilation-induced lung injury, pneumonias, and sepsis. The therapeutic benefits of CO may extend to other diseases involving aberrant inflammatory processes such as transplant-associated ischemia/reperfusion injury and chronic graft rejection, and metabolic diseases. Current and planned clinical trials explore the therapeutic benefit of CO in ARDS and other lung diseases. Full article
(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1)
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Open AccessArticle
Antioxidants N-Acetylcysteine and Vitamin C Improve T Cell Commitment to Memory and Long-Term Maintenance of Immunological Memory in Old Mice
Antioxidants 2020, 9(11), 1152; https://doi.org/10.3390/antiox9111152 - 19 Nov 2020
Viewed by 355
Abstract
Aging is characterized by reduced immune responses, a process known as immunosenescence. Shortly after their generation, antigen-experienced adaptive immune cells, such as CD8+ and CD4+ T cells, migrate into the bone marrow (BM), in which they can be maintained for long [...] Read more.
Aging is characterized by reduced immune responses, a process known as immunosenescence. Shortly after their generation, antigen-experienced adaptive immune cells, such as CD8+ and CD4+ T cells, migrate into the bone marrow (BM), in which they can be maintained for long periods of time within survival niches. Interestingly, we recently observed how oxidative stress may negatively support the maintenance of immunological memory in the BM in old age. To assess whether the generation and maintenance of immunological memory could be improved by scavenging oxygen radicals, we vaccinated 18-months (old) and 3-weeks (young) mice with alum-OVA, in the presence/absence of antioxidants vitamin C (Vc) and/or N-acetylcysteine (NAC). To monitor the phenotype of the immune cell population, blood was withdrawn at several time-points, and BM and spleen were harvested 91 days after the first alum-OVA dose. Only in old mice, memory T cell commitment was boosted with some antioxidant treatments. In addition, oxidative stress and the expression of pro-inflammatory molecules decreased in old mice. Finally, changes in the phenotype of dendritic cells, important regulators of T cell activation, were additionally observed. Taken together, our data show that the generation and maintenance of memory T cells in old age may be improved by targeting oxidative stress. Full article
(This article belongs to the Special Issue Cellular Oxidative Stress)
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Open AccessReview
The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies
Antioxidants 2020, 9(11), 1151; https://doi.org/10.3390/antiox9111151 - 19 Nov 2020
Viewed by 314
Abstract
Cancer remains an elusive, highly complex disease and a global burden. Constant change by acquired mutations and metabolic reprogramming contribute to the high inter- and intratumor heterogeneity of malignant cells, their selective growth advantage, and their resistance to anticancer therapies. In the modern [...] Read more.
Cancer remains an elusive, highly complex disease and a global burden. Constant change by acquired mutations and metabolic reprogramming contribute to the high inter- and intratumor heterogeneity of malignant cells, their selective growth advantage, and their resistance to anticancer therapies. In the modern era of integrative biomedicine, realizing that a personalized approach could benefit therapy treatments and patients’ prognosis, we should focus on cancer-driving advantageous modifications. Namely, reactive oxygen species (ROS), known to act as regulators of cellular metabolism and growth, exhibit both negative and positive activities, as do antioxidants with potential anticancer effects. Such complexity of oxidative homeostasis is sometimes overseen in the case of studies evaluating the effects of potential anticancer antioxidants. While cancer cells often produce more ROS due to their increased growth-favoring demands, numerous conventional anticancer therapies exploit this feature to ensure selective cancer cell death triggered by excessive ROS levels, also causing serious side effects. The activation of the cellular NRF2 (nuclear factor erythroid 2 like 2) pathway and induction of cytoprotective genes accompanies an increase in ROS levels. A plethora of specific targets, including those involved in thioredoxin (TRX) and glutathione (GSH) systems, are activated by NRF2. In this paper, we briefly review preclinical research findings on the interrelated roles of the NRF2 pathway and TRX and GSH systems, with focus given to clinical findings and their relevance in carcinogenesis and anticancer treatments. Full article
(This article belongs to the Special Issue Anticancer Antioxidants)
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Open AccessReview
Therapeutic Potential of Heme Oxygenase-1 in Aneurysmal Diseases
Antioxidants 2020, 9(11), 1150; https://doi.org/10.3390/antiox9111150 - 19 Nov 2020
Viewed by 268
Abstract
Abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA) are serious arterial diseases in the aorta and brain, respectively. AAA and IA are associated with old age in males and females, respectively, and if rupture occurs, they carry high morbidity and mortality. Aneurysmal subarachnoid [...] Read more.
Abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA) are serious arterial diseases in the aorta and brain, respectively. AAA and IA are associated with old age in males and females, respectively, and if rupture occurs, they carry high morbidity and mortality. Aneurysmal subarachnoid hemorrhage (SAH) due to IA rupture has a high rate of complication and fatality. Despite these severe clinical outcomes, preventing or treating these devastating diseases remains an unmet medical need. Inflammation and oxidative stress are shared pathologies of these vascular diseases. Therefore, therapeutic strategies have focused on reducing inflammation and reactive oxygen species levels. Interestingly, in response to cellular stress, the inducible heme oxygenase-1 (HO-1) is highly upregulated and protects against tissue injury. HO-1 degrades the prooxidant heme and generates molecules with antioxidative and anti-inflammatory properties, resulting in decreased oxidative stress and inflammation. Therefore, increasing HO-1 activity is an attractive option for therapy. Several HO-1 inducers have been identified and tested in animal models for preventing or alleviating AAA, IA, and SAH. However, clinical trials have shown conflicting results. Further research and the development of highly selective HO-1 regulators may be needed to prevent the initiation and progression of AAA, IA, or SAH. Full article
(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1)
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Open AccessArticle
Alpha-Glucosidase and Alpha-Amylase Inhibitory Activities, Molecular Docking, and Antioxidant Capacities of Salvia aurita Constituents
Antioxidants 2020, 9(11), 1149; https://doi.org/10.3390/antiox9111149 - 19 Nov 2020
Viewed by 269
Abstract
Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with a high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristics of DM. Due to the detrimental [...] Read more.
Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with a high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristics of DM. Due to the detrimental side effects of the current treatment, there is a considerable need to develop new effective antidiabetic drugs, especially alpha-glucosidase and alpha-amylase inhibitors with lesser adverse effects. These inhibitors are known to be directly involved in the delay of carbohydrate digestion, resulting in a reduction of glucose absorption rate and, consequently, reducing the postprandial rise of plasma glucose, which can reduce the risk of long-term diabetes complications. Furthermore, natural products are well-known sources for the discovery of new bioactive compounds that can serve as scaffolds for drug discovery, including that of new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach Pass, Eastern Cape Province, South Africa (SA), yielded four known abietane diterpenes namely carnosol (1), rosmanol (2), 7-methoxyrosmanol (3), 12-methoxycarnosic acid (4), and one flavonoid named 4,7-dimethylapigenin (5). Structural characterization of these isolated compounds was conducted using 1 and 2D NMR, in comparison with reported spectroscopic data. These compounds are reported for the first time from S. aurita. The biological evaluation of the isolated compound against alpha-glucosidase exhibited strong inhibitory activities for 3 and 2 with the half maximal inhibitory concentration (IC50) values of 4.2 ± 0.7 and 16.4 ± 1.1 µg/mL respectively, while 4 and 1 demonstrated strong alpha-amylase inhibitory activity amongst the isolated compounds with IC50 values of 16.2 ± 0.3 and 19.8 ± 1.4 µg/mL. Molecular docking analysis confirms the strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1, and 3, respectively, with oxygen radical absorbance capacity (ORAC) (25.79 ± 0.01; 23.96 ± 0.01; 23.94 ± 0.02) mM Trolox equivalent (TE)/g; 1 and 2 as ferric-ion reducing antioxidant power (FRAP) (3.92 ± 0.002; 1.52 ± 0.002) mM ascorbic acid equivalent (AAE)/g; 5 and 2 as Trolox equivalent absorbance capacity (TEAC) (3.19 ± 0.003; 2.06 ± 0.003) mM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and antidiabetic activities that can be useful to modulate oxidative stress and might possibly be excellent candidates for the management of diabetes. This is the first scientific report on the phytochemical isolation and biological evaluation of the alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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Open AccessArticle
Antioxidant Activity and Acteoside Analysis of Abeliophyllum distichum
Antioxidants 2020, 9(11), 1148; https://doi.org/10.3390/antiox9111148 - 19 Nov 2020
Viewed by 167
Abstract
This study determined acteoside and its content in Abeliophyllum distichum via HPLC/UV and LC/ESI-MS to obtain insights into the potential use of this plant as an antioxidant agent. Moreover, 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and O2 radical scavenging activity assays [...] Read more.
This study determined acteoside and its content in Abeliophyllum distichum via HPLC/UV and LC/ESI-MS to obtain insights into the potential use of this plant as an antioxidant agent. Moreover, 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and O2 radical scavenging activity assays were performed to assess in vitro antioxidative activity. The DPPH, OH, and O2 radical scavenging activities of A. distichum leaf EtOH extracts at a 250 μg/mL concentration were 88.32%, 94.48%, and 14.36%, respectively, whereas those of stem extracts at the same concentration were 88.15%, 88.99%, and 15.36%, respectively. The contents of acteoside in A. distichum leaves and stems were 162.11 and 29.68 mg/g, respectively. Acteoside was identified as the main antioxidant compound in A. distichum leaves, which resulted in DPPH, OH, and O2 radical scavenging activities of 82.84%, 89.46%, and 30.31%, respectively, at a 25 μg/mL concentration. These results indicate that A. distichum leaves and stems containing the antioxidant acteoside can be used as natural ingredients for functional and nutritional supplements. Full article
(This article belongs to the Special Issue Antioxidants of Natural Product)
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Open AccessArticle
Synthesis and Characterization of Green Carbon Dots for Scavenging Radical Oxygen Species in Aqueous and Oil Samples
Antioxidants 2020, 9(11), 1147; https://doi.org/10.3390/antiox9111147 - 19 Nov 2020
Viewed by 196
Abstract
Carbon dots (CDs) due to their unique optical features, chemical stability and low environmental hazard are applied in different fields such as metal ion sensing, photo-catalysis, bio-imaging and tribology, among others. The aims of the present research were to obtain CDs from vegetable [...] Read more.
Carbon dots (CDs) due to their unique optical features, chemical stability and low environmental hazard are applied in different fields such as metal ion sensing, photo-catalysis, bio-imaging and tribology, among others. The aims of the present research were to obtain CDs from vegetable wastes (tea and grapes) as carbon sources and to explore their potential properties as radical scavengers. CDs from glutathione/citric acid (GCDs) were synthetized for comparison purposes. The CDs were investigated for their chemical structure, morphology, optical and electronical properties. The antioxidant activity has been explored by DPPH and Folin-Ciocelteau assays in aqueous media. Due to their solubility in oil, the CDs prepared from tea wastes and GCDs were assayed as antioxidants in a mineral oil lubricant by potentiometric determination of the peroxide value. CDs from tea wastes and GCDs exhibited good antioxidant properties both in aqueous and oil media. Possible mechanisms, such as C-addition to double bonds, H-abstraction and SOMO-CDs conduction band interaction, were proposed for the CDs radical scavenging activity. CDs from natural sources open new application pathways as antioxidant green additives. Full article
(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)
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Open AccessReview
Systematic Review and Meta-Analysis of the Blood Glutathione Redox State in Chronic Obstructive Pulmonary Disease
Antioxidants 2020, 9(11), 1146; https://doi.org/10.3390/antiox9111146 - 18 Nov 2020
Viewed by 344
Abstract
The aim of this systematic review and meta-analysis was to assess the blood concentrations of the total and reduced forms of the low-molecular-weight antioxidant thiol glutathione (GSH) in chronic obstructive pulmonary disease (COPD) patients in comparison to healthy individuals. A literature search was [...] Read more.
The aim of this systematic review and meta-analysis was to assess the blood concentrations of the total and reduced forms of the low-molecular-weight antioxidant thiol glutathione (GSH) in chronic obstructive pulmonary disease (COPD) patients in comparison to healthy individuals. A literature search was conducted in the PubMed and Web of Science databases from inception until June 2020. In the 18 studies identified (involving a total of 974 COPD patients and 631 healthy controls), the pooled reduced GSH concentrations were significantly lower in patients with COPD than controls (SMD  =  −3.04, 95% CI = −4.42 to −1.67; p  <  0.001). By contrast, the pooled total GSH concentrations were significantly higher in patients with COPD than controls (SMD = 0.42, 95% CI = 0.11 to 0.73; p = 0.009). Our meta-analysis showed that the blood concentrations of reduced GSH, even in the presence of higher total GSH concentrations, were significantly lower in patients with COPD when compared to healthy controls. This suggests that an impaired antioxidant defense system plays an important role in the pathogenesis of COPD. Full article
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Open AccessArticle
Oxidative Stress in Endurance Cycling Is Reduced Dose-Dependently after One Month of Re-Esterified DHA Supplementation
Antioxidants 2020, 9(11), 1145; https://doi.org/10.3390/antiox9111145 - 18 Nov 2020
Viewed by 278
Abstract
Docosahexaenoic acid (DHA) supplementation can reduce exercise-induced oxidative stress generated during long aerobic exercise, with the minimum dose yet to be elucidated for physically active subjects. In this study, we performed a dose finding with re-esterified DHA in triglyceride form in a randomized [...] Read more.
Docosahexaenoic acid (DHA) supplementation can reduce exercise-induced oxidative stress generated during long aerobic exercise, with the minimum dose yet to be elucidated for physically active subjects. In this study, we performed a dose finding with re-esterified DHA in triglyceride form in a randomized double-blind parallel trial at different doses (350, 1050, 1750, and 2450 mg a day) for 4 weeks in males engaged in regular cycling (n = 100, 7.6 ± 3.7 h/week). The endogenous antioxidant capacity of DHA was quantified as a reduction in the levels of the oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-OHdG) recollected in 24-h urine samples after 90 min of constant load cycling before and after intervention. To ascertain incorporation of DHA, erythrocyte polyunsaturated fatty acid (PUFA) composition was compared along groups. We found a dose-dependent antioxidant capacity of DHA from 1050 mg with a trend to neutralization for the highest dose of 2450 mg (placebo: n = 13, F = 0.041; 350 mg: n = 10, F = 0.268; 1050 mg: n = 11, F = 7.112; 1750 mg: n = 12, F = 9.681; 2450 mg: n = 10, F = 15.230). In the erythrocyte membrane, the re-esterified DHA increased DHA and omega-3 percentage and decreased omega 6 and the omega-6 to omega-3 ratio, while Eicosapentaenoic acid (EPA) and PUFA remained unchanged. Supplementation of re-esterified DHA exerts a dose-dependent endogenous antioxidant property against moderate-intensity long-duration aerobic exercise in physically active subjects when provided at least 1050 mg a day for 4 weeks. Full article
(This article belongs to the Special Issue Oxidative Stress in Skeletal Muscle)
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Open AccessArticle
Oxidative Chemical Stressors Alter the Physiological State of the Nasal Olfactory Mucosa of Atlantic Salmon
Antioxidants 2020, 9(11), 1144; https://doi.org/10.3390/antiox9111144 - 18 Nov 2020
Viewed by 296
Abstract
The olfactory organs of fish have vital functions for chemosensory and defence. Though there have been some ground-breaking discoveries of their involvement in immunity against pathogens in recent years, little is known about how they respond to non-infectious agents, such as exogenous oxidants, [...] Read more.
The olfactory organs of fish have vital functions for chemosensory and defence. Though there have been some ground-breaking discoveries of their involvement in immunity against pathogens in recent years, little is known about how they respond to non-infectious agents, such as exogenous oxidants, which fish encounter regularly. To this end, we employed Atlantic salmon (Salmo salar) as a model to study the molecular responses at the nasal olfactory mucosa of a teleost fish when challenged with oxidants. Microarray analysis was employed to unravel the transcriptional changes at the nasal olfactory mucosa following two types of in vivo exposure to peracetic acid (PAA), a highly potent oxidative agent commonly used in aquaculture: Trial 1: periodic and low dose (1 ppm, every 3 days over 45 days) to simulate a routine disinfection; and Trial 2: less frequent and high dose (10 ppm for 30 min, every 15 days, 3 times) to mimic a bath treatment. Furthermore, leukocytes from the olfactory organ were isolated and exposed to PAA, as well as to hydrogen peroxide (H2O2) and acetic acid (AA)—the two other components of PAA trade products—to perform targeted cellular and molecular response profiling. In the first trial, microarrays identified 32 differentially expressed genes (DEG) after a 45-day oxidant exposure. Erythrocyte-specific genes were overly represented and substantially upregulated following exogenous oxidant exposure. In Trial 2, in which a higher dose was administered, 62 DEGs were identified, over 80% of which were significantly upregulated after exposure. Genes involved in immune response, redox balance and stress, maintenance of cellular integrity and extracellular matrix were markedly affected by the oxidant. All chemical stimuli (i.e., PAA, H2O2, AA) significantly affected the proliferation of nasal leukocytes, with indications of recovery observed in PAA- and H2O2-exposed cells. The migration of nasal leukocytes was promoted by H2O2, but not much by PAA and AA. The three chemical oxidative stressors triggered oxidative stress in nasal leukocytes as indicated by an increase in the intracellular reactive oxygen species level. This resulted in the mobilisation of antioxidant defences in the nasal leukocytes as shown by the upregulation of crucial genes for this response network. Though qPCR revealed changes in the expression of selected cytokines and heat shock protein genes following in vitro challenge, the responses were stochastic. The results from the study advance our understanding of the role that the nasal olfactory mucosa plays in host defence, particularly towards oxidative chemical stressors. Full article
(This article belongs to the Special Issue Cellular Oxidative Stress)
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Open AccessArticle
Melatonin Can Modulate the Effect of Navitoclax (ABT-737) in HL-60 Cells
Antioxidants 2020, 9(11), 1143; https://doi.org/10.3390/antiox9111143 - 18 Nov 2020
Viewed by 244
Abstract
Melatonin (N-acetyl-5-methoxytryptamine MEL) is an indolamine that has antioxidant, anti-inflammatory and anti-tumor properties. Moreover, MEL is capable of exhibiting both anti-apoptotic and pro-apoptotic effects. In the normal cells, MEL possesses antioxidant property and has an anti-apoptotic effect, while in the cancer [...] Read more.
Melatonin (N-acetyl-5-methoxytryptamine MEL) is an indolamine that has antioxidant, anti-inflammatory and anti-tumor properties. Moreover, MEL is capable of exhibiting both anti-apoptotic and pro-apoptotic effects. In the normal cells, MEL possesses antioxidant property and has an anti-apoptotic effect, while in the cancer cells it has pro-apoptotic action. We investigated the combined effect of MEL and navitoclax (ABT-737), which promotes cell death, on the activation of proliferation in acute promyelocytic leukemia on a cell model HL-60. The combined effect of these compounds leads to a reduction of the index of mitotic activity. The alterations in the level of anti- and pro-apoptotic proteins such as BclxL, Bclw, Mcl-1, and BAX, membrane potential, Ca2+ retention capacity, and ROS production under the combined action of MEL and ABT-737 were performed. We obtained that MEL in combination with ABT-737 decreased Ca2+ capacity, dropped membrane potential, increased ROS production, suppressed the expression of anti-apoptotic proteins such as BclxL, Bclw, and Mcl-1, and enhanced the expression of pro-apoptotic BAX. Since, MEL modulates autophagy and endoplasmic reticulum (ER) stress in cancer cells, the combined effect of MEL and ABT-737 on the expression of ER stress and autophagy markers was checked. The combined effect of MEL and ABT-737 (0.2 μM) increased the expression of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), leading to a decrease in the level of binding immunoglobulin protein (BIP) followed by an increase in the level of C/EBP homologous protein (CHOP). In this condition, the expression of ERO1 decreased, which could lead to a decrease in the level of protein disulfide isomerase (PDI). The obtained data suggested that melatonin has potential usefulness in the treatment of cancer, where it is able to modulate ER stress, autophagy and apoptosis. Full article
(This article belongs to the Special Issue Role of Antioxidant Molecules and Melatonin in Cellular Protection)
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Open AccessReview
Targeted Antioxidants in Exercise-Induced Mitochondrial Oxidative Stress: Emphasis on DNA Damage
Antioxidants 2020, 9(11), 1142; https://doi.org/10.3390/antiox9111142 - 17 Nov 2020
Viewed by 550
Abstract
Exercise simultaneously incites beneficial (e.g., signal) and harming (e.g., damage to macromolecules) effects, likely through the generation of reactive oxygen and nitrogen species (RONS) and downstream changes to redox homeostasis. Given the link between nuclear DNA damage and human longevity/pathology, research attempting to [...] Read more.
Exercise simultaneously incites beneficial (e.g., signal) and harming (e.g., damage to macromolecules) effects, likely through the generation of reactive oxygen and nitrogen species (RONS) and downstream changes to redox homeostasis. Given the link between nuclear DNA damage and human longevity/pathology, research attempting to modulate DNA damage and restore redox homeostasis through non-selective pleiotropic antioxidants has yielded mixed results. Furthermore, until recently the role of oxidative modifications to mitochondrial DNA (mtDNA) in the context of exercising humans has largely been ignored. The development of antioxidant compounds which specifically target the mitochondria has unveiled a number of exciting avenues of exploration which allow for more precise discernment of the pathways involved with the generation of RONS and mitochondrial oxidative stress. Thus, the primary function of this review, and indeed its novel feature, is to highlight the potential roles of mitochondria-targeted antioxidants on perturbations to mitochondrial oxidative stress and the implications for exercise, with special focus on mtDNA damage. A brief synopsis of the current literature addressing the sources of mitochondrial superoxide and hydrogen peroxide, and available mitochondria-targeted antioxidants is also discussed. Full article
(This article belongs to the Special Issue Mitochondrial Reactive Oxygen Species)
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Open AccessReview
The Antioxidant Role of One-Carbon Metabolism on Stroke
Antioxidants 2020, 9(11), 1141; https://doi.org/10.3390/antiox9111141 - 17 Nov 2020
Viewed by 275
Abstract
One-carbon (1C) metabolism is a metabolic network that is centered on folate, a B vitamin; it integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. This metabolic pathway also reduces levels of homocysteine, a non-protein amino acid. High levels of homocysteine are linked [...] Read more.
One-carbon (1C) metabolism is a metabolic network that is centered on folate, a B vitamin; it integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. This metabolic pathway also reduces levels of homocysteine, a non-protein amino acid. High levels of homocysteine are linked to increased risk of hypoxic events, such as stroke. Several preclinical studies have suggested that 1C metabolism can impact stroke outcome, but the clinical data are unclear. The objective of this paper was to review preclinical and clinical research to determine whether 1C metabolism has an antioxidant role on stroke. To accomplish the objective, we searched for publications using the following medical subject headings (MeSH) keywords: antioxidants, hypoxia, stroke, homocysteine, one-carbon metabolism, folate, methionine, and dietary supplementation of one-carbon metabolism. Both pre-clinical and clinical studies were retrieved and reviewed. Our review of the literature suggests that deficiencies in 1C play an important role in the onset and outcome of stroke. Dietary supplementation of 1C provides beneficial effects on stroke outcome. For stroke-affected patients or individuals at high risk for stroke, the data suggest that nutritional modifications in addition to other therapies could be incorporated into a treatment plan. Full article
(This article belongs to the Special Issue Hypoxia-Induced Oxidative Stress in the Brain)
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Open AccessArticle
Suppression of Methane Generation during Methanogenesis by Chemically Modified Humic Compounds
Antioxidants 2020, 9(11), 1140; https://doi.org/10.3390/antiox9111140 - 17 Nov 2020
Viewed by 201
Abstract
The introduction of various concentrations of chemically modified humic compounds (HC) with different redox characteristics into the media with free and immobilized anaerobic consortia accumulating landfill gases was studied as approach to their functioning management. For this purpose, quinone (hydroquinone, naphthoquinone or methylhydroquinone) [...] Read more.
The introduction of various concentrations of chemically modified humic compounds (HC) with different redox characteristics into the media with free and immobilized anaerobic consortia accumulating landfill gases was studied as approach to their functioning management. For this purpose, quinone (hydroquinone, naphthoquinone or methylhydroquinone) derivatives of HC were synthesized, which made it possible to vary the redox and antioxidant properties of HC as terminal electron acceptors in methanogenic systems. The highest acceptor properties were obtained with potassium humate modified by naphthoquinone. To control possible negative effect of HC on the cells of natural methanogenic consortia, different bioluminescent analytical methods were used. The addition of HC derivatives, enriched with quinonones, to nutrient media at concentrations above 1 g/L decreased the energetic status of cells and the efficiency of the methanogenesis. For the first time, the significant decrease in accumulation of biogas was reached as effect of synthetic HC derivatives, whereas both notable change of biogas composition towards increase in the CO2 content and decrease in CH4 were revealed. Thus, modification with quinones makes it possible to obtain low-potential HC derivatives with strongly pronounced acceptor properties, promising for inhibition of biogas synthesis by methanogenic communities. Full article
(This article belongs to the Special Issue Redox Biology in Microorganisms)
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