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Antioxidants, Volume 11, Issue 7 (July 2022) – 205 articles

Cover Story (view full-size image): Methionine-rich prion-like proteins can regulate liquid–liquid phase separation processes in response to stresses. To date, however, very few proteins have been identified as being methionine-rich and prion-like. Herein, we have performed a computational survey of the human proteome to search for methionine-rich prion-like domains. We present a census of 51 manually curated methionine-rich prion-like proteins. View this paper
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Article
Antioxidant Effects of DPP-4 Inhibitors in Early Stages of Experimental Diabetic Retinopathy
Antioxidants 2022, 11(7), 1418; https://doi.org/10.3390/antiox11071418 - 21 Jul 2022
Viewed by 451
Abstract
Hyperglycemia-induced oxidative stress plays a key role in the impairment of the retinal neurovascular unit, an early event in the pathogenesis of DR. The aim of this study was to assess the antioxidant properties of topical administration (eye drops) of sitagliptin in the [...] Read more.
Hyperglycemia-induced oxidative stress plays a key role in the impairment of the retinal neurovascular unit, an early event in the pathogenesis of DR. The aim of this study was to assess the antioxidant properties of topical administration (eye drops) of sitagliptin in the diabetic retina. For this purpose, db/db mice received sitagliptin or vehicle eye drops twice per day for two weeks. Age-matched db/+ mice were used as the control group. We evaluated retinal mRNA (RT-PCR) and protein levels (Western blotting and immunohistochemistry) of different components from both the antioxidant system (NRF2, CAT, GPX, GR, CuZnSOD, and MnSOD) and the prooxidant machinery (PKC and TXNIP). We also studied superoxide levels (dihydroethidium staining) and oxidative damage to DNA/RNA (8-hydroxyguanosine immunostaining) and proteins (nitrotyrosine immunostaining). Finally, NF-кB translocation and IL-1β production were assessed through Western blotting and/or immunohistochemistry. We found that sitagliptin protected against diabetes-induced oxidative stress by reducing superoxide, TXNIP, PKC, and DNA/RNA/protein oxidative damage, and it prevented the downregulation of NRF2 and antioxidant enzymes, with the exception of catalase. Sitagliptin also exerted anti-inflammatory effects, avoiding both NF-кB translocation and IL-1β production. Sitagliptin prevents the diabetes-induced imbalance between ROS production and antioxidant defenses that occurs in diabetic retinas. Full article
(This article belongs to the Special Issue Oxidative Stress and Retinal Diseases)
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Article
Antioxidant-Loaded Mesoporous Silica—An Evaluation of the Physicochemical Properties
Antioxidants 2022, 11(7), 1417; https://doi.org/10.3390/antiox11071417 - 21 Jul 2022
Viewed by 358
Abstract
The dangerous effects of oxidative stress can be alleviated by antioxidants—substances with the ability to prevent damage caused by reactive oxygen species. The adsorption of antioxidants onto nanocarriers is a well-known method that might protect them against rough environ-mental conditions. The aim of [...] Read more.
The dangerous effects of oxidative stress can be alleviated by antioxidants—substances with the ability to prevent damage caused by reactive oxygen species. The adsorption of antioxidants onto nanocarriers is a well-known method that might protect them against rough environ-mental conditions. The aim of this study was to investigate the adsorption and desorption of gallic acid (GA), protocatechuic acid (PCA), chlorogenic acid (CGA), and 4-hydroxybenzoic acid (4-HBA) using commercially available mesoporous silica materials (MSMs), both parent (i.e., SBA-15 and MCM-41) and surface functionalized (i.e., SBA-NH2 and SBA-SH). The MSMs loaded with active compounds were characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), thermoporometry (TPM), and powder X-ray diffraction (XRD). High-performance liquid chromatography (HPLC-CAD) was used to evaluate the performance of the adsorption and desorption processes. The antioxidant potential was investigated using the Folin–Ciocalteu (FC) spectrophotometric method. Among the studied MSMs, the highest adsorption of GA was observed for amine-modified SBA-15 mesoporous silica. The adsorption capacity of SBA-NH2 increased in the order of PCA, 4-HBA < GA < CGA. Different desorption effectiveness levels of the adsorbed compounds were observed with the antioxidant capacity preserved for all investigated compounds. Full article
(This article belongs to the Special Issue Antioxidants in Human Health and Disease)
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Article
Inhibition of Cell Proliferation and Cell Viability by Sinecatechins in Cutaneous SCC Cells Is Related to an Imbalance of ROS and Loss of Mitochondrial Membrane Potential
Antioxidants 2022, 11(7), 1416; https://doi.org/10.3390/antiox11071416 - 21 Jul 2022
Viewed by 444
Abstract
The term sinecatechins designates an extract containing a high percentage of catechins obtained from green tea, which is commercially registered as Veregen or Polyphenon E (PE) and may be considered for treatment of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK). As [...] Read more.
The term sinecatechins designates an extract containing a high percentage of catechins obtained from green tea, which is commercially registered as Veregen or Polyphenon E (PE) and may be considered for treatment of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK). As shown here, treatment of four cSCC cell lines with 200 µg/mL of PE resulted in strong, dose-dependent decrease in cell proliferation (20–30%) as well as strongly decreased cell viability (4–21% of controls, 48 h). Effects correlated with loss of mitochondrial membrane potential, whereas early apoptosis was less pronounced. At the protein level, some activation of caspase-3 and enhanced expression of the CDK inhibitor p21 were found. Loss of MMP and induced cell death were, however, largely independent of caspases and of the proapoptotic Bcl-2 proteins Bax and Bak, suggesting that sinecatechins induce also non-apoptotic, alternative cell death pathways, in addition to apoptosis. Reactive oxygen species (ROS) were downregulated in response to PE at 4 h, followed by an increase at 24 h. The contributory role of initially reduced ROS was supported by the antioxidant N-acetyl cysteine, which in combination with PE further enhanced the negative effects on cell viability. Thus, sinecatechins inhibited cell proliferation and viability of cSCC cells, which could suggest the use of PE for AK treatment. The mechanisms appear as linked to an imbalance of ROS levels. Full article
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Article
Ultra-Processed Food Consumption during Pregnancy and Its Association with Maternal Oxidative Stress Markers
Antioxidants 2022, 11(7), 1415; https://doi.org/10.3390/antiox11071415 - 21 Jul 2022
Viewed by 597
Abstract
Ultra-processed food (UPF) consumption during gestation may lead to increased oxidative stress (OS) and could affect pregnancy outcomes. This study aims to evaluate the association of UPF consumption during pregnancy with circulating levels of OS markers. Diet was assessed (average of three assessments) [...] Read more.
Ultra-processed food (UPF) consumption during gestation may lead to increased oxidative stress (OS) and could affect pregnancy outcomes. This study aims to evaluate the association of UPF consumption during pregnancy with circulating levels of OS markers. Diet was assessed (average of three assessments) in 119 pregnant women enrolled in the OBESO perinatal cohort (Mexico), obtaining quantitative data and the percentage of energy that UPFs (NOVA) contributed to the total diet. Sociodemographic, clinical (pregestational body-mass index and gestational weight gain) and lifestyle data were collected. Maternal circulating levels of OS markers (malondialdehyde (MDA), protein carbonylation (PC), and total antioxidant capacity (TAC)) were determined at the third trimester of pregnancy. Adjusted linear regression models were performed to analyze the association between UPFs and OS markers. UPFs represented 27.99% of the total energy intake. Women with a lower UPF consumption (<75 percentile°) presented a higher intake of fiber, ω-3, ω-6, and a lower ω-6/3 ratio. Linear regression models showed that UPFs were inversely associated with TAC and MDA. Fiber intake was associated with PC. UPF intake during pregnancy may result in an increase in oxidative stress. When providing nutrition care, limiting or avoiding UPFs may be an intervention strategy that could promote a better antioxidant capacity in the body. Full article
Article
Salidroside Ameliorates Radiation Damage by Reducing Mitochondrial Oxidative Stress in the Submandibular Gland
Antioxidants 2022, 11(7), 1414; https://doi.org/10.3390/antiox11071414 - 21 Jul 2022
Viewed by 366
Abstract
Radiotherapy for patients with head and neck cancer inevitably causes radiation damage to salivary glands (SGs). Overproduction of reactive oxygen species (ROS) leads to mitochondrial damage and is critical in the pathophysiology of SG radiation damage. However, mitochondrial-targeted treatment is unavailable. Herein, both [...] Read more.
Radiotherapy for patients with head and neck cancer inevitably causes radiation damage to salivary glands (SGs). Overproduction of reactive oxygen species (ROS) leads to mitochondrial damage and is critical in the pathophysiology of SG radiation damage. However, mitochondrial-targeted treatment is unavailable. Herein, both in vitro and in vivo models of radiation-damaged rat submandibular glands (SMGs) were used to investigate the potential role of salidroside in protecting irradiated SGs. Cell morphology was observed with an inverted phase-contrast microscope. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), mitochondrial ROS, mitochondrial membrane potential (MMP), and ATP were measured using relevant kits. The mitochondrial ultrastructure was observed under transmission electron microscopy. Cell apoptosis was determined by Western blot and TUNEL assays. Saliva was measured from Wharton’s duct. We found that salidroside protected SMG cells and tissues against radiation and improved the secretion function. Moreover, salidroside enhanced the antioxidant defense by decreasing MDA, increasing SOD, CAT, and GSH, and scavenging mitochondrial ROS. Furthermore, salidroside rescued the mitochondrial ultrastructure, preserved MMP and ATP, suppressed cytosolic cytochrome c and cleaved caspase 3 expression, and inhibited cell apoptosis. Together, these findings first identify salidroside as a mitochondrial-targeted antioxidant for preventing SG radiation damage. Full article
(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)
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Article
Chemical Profiling, Antioxidant, and Antimicrobial Activity of Saudi Propolis Collected by Arabian Honey Bee (Apis mellifera jemenitica) Colonies
Antioxidants 2022, 11(7), 1413; https://doi.org/10.3390/antiox11071413 - 21 Jul 2022
Viewed by 398
Abstract
Propolis (bee glue) is a complex, phyto-based resinous material obtained from beehives. Its chemical and biological properties vary with respect to bee species, type of plants, geographical location, and climate of a particular area. This study was planned with the aim of determining [...] Read more.
Propolis (bee glue) is a complex, phyto-based resinous material obtained from beehives. Its chemical and biological properties vary with respect to bee species, type of plants, geographical location, and climate of a particular area. This study was planned with the aim of determining the chemical composition and to investigate various properties (against oxidants and microbes) of different extracts of Saudi propolis collected from Arabian honey bee (Apis mellifera jemenitica) colonies headed by young queens. Chemical analysis of propolis extracts with different solvents, i.e., ethyl acetate (Eac), methanol (Met), butanol (BuT), and hexane (Hex) was done through colorimetry for the total phenolic content (TPC) and total flavonoid content (TFC) evaluation. For separation and extensive characterization of the Met extract, chromatography and 1H NMR were deployed. Six different microorganisms were selected to analyze the Saudi-propolis-based extract’s antimicrobial nature by measuring zones of inhibition (ZOI) and minimum inhibitory concentration (MIC). Molecular docking was done by utilizing AutodDock, and sketching of ligands was performed through Marvin Chem Sketch (MCS), and the resultant data after 2D and 3D clean were stored in .mol format. The highest TFC (96.65 mg quercetin equivalents (QE)/g of propolis) and TPC (325 mg gallic acid equivalents (GAE)/g of propolis) were noted for Met. Six familiar compounds were isolated, and recognition was done with NMR. Met extract showed the greatest 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) free radical scavenging activity and Ferric Reducing Antioxidant Power (FRAP). Met showed max microbial activity against Staphylococcus aureus (ZOI = 18.67 mm, MIC = 0.625 mg/mL), whereas the minimum was observed in Hex against E. coli (ZOI = 6.33 mm, MIC = 2.50 mg/mL). Furthermore, the molecular docking process established the biological activity of separated compounds against HCK (Hematopoietic cell kinase) and Gyrase B of S. aureus. Moreover, the stability of protein–ligand complexes was further established through molecular dynamic simulation studies, which showed that the receptor–ligand complexes were quite stable. Results of this research will pave the way for further consolidated analysis of propolis obtained from Arabian honey bees (A. m. jemenitica). Full article
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Systematic Review
Walnut Intake Interventions Targeting Biomarkers of Metabolic Syndrome and Inflammation in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Antioxidants 2022, 11(7), 1412; https://doi.org/10.3390/antiox11071412 - 21 Jul 2022
Viewed by 515
Abstract
Biomarkers of metabolic syndrome and inflammation are pathophysiological predictors and factors of senescence and age-related diseases. Recent evidence showed that particular diet components, such as walnuts rich in antioxidant bioactive compounds and with a balanced lipid profile, could have positive outcomes on human [...] Read more.
Biomarkers of metabolic syndrome and inflammation are pathophysiological predictors and factors of senescence and age-related diseases. Recent evidence showed that particular diet components, such as walnuts rich in antioxidant bioactive compounds and with a balanced lipid profile, could have positive outcomes on human health. A systematic search in PubMed, EMBASE, Cochrane Library, Scopus, and ClinicalTrials.gov databases was performed to retrieve randomized controlled trials published from the beginning of each database through November 2021, reporting on the outcomes of walnut consumption over 22 metabolic syndrome and inflammatory markers in middle-aged and older adults. The search strategy rendered 17 studies in the final selection, including 11 crossover and 6 parallel trials. The study revealed that walnut-enriched diets had statistically significant decreasing effects for triglyceride, total cholesterol, and LDL cholesterol concentrations on some inflammatory markers and presented no consequences on anthropometric and glycemic parameters. Although further studies and better-designed ones are needed to strengthen these findings, the results emphasize the benefits of including walnuts in the dietary plans of this age group. Full article
(This article belongs to the Special Issue Antioxidants in Age-Related Diseases and Anti-Aging Strategies)
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Review
Focus on Nitric Oxide Homeostasis: Direct and Indirect Enzymatic Regulation of Protein Denitrosation Reactions in Plants
Antioxidants 2022, 11(7), 1411; https://doi.org/10.3390/antiox11071411 - 21 Jul 2022
Viewed by 400
Abstract
Protein cysteines (Cys) undergo a multitude of different reactive oxygen species (ROS), reactive sulfur species (RSS), and/or reactive nitrogen species (RNS)-derived modifications. S-nitrosation (also referred to as nitrosylation), the addition of a nitric oxide (NO) group to reactive Cys thiols, can alter [...] Read more.
Protein cysteines (Cys) undergo a multitude of different reactive oxygen species (ROS), reactive sulfur species (RSS), and/or reactive nitrogen species (RNS)-derived modifications. S-nitrosation (also referred to as nitrosylation), the addition of a nitric oxide (NO) group to reactive Cys thiols, can alter protein stability and activity and can result in changes of protein subcellular localization. Although it is clear that this nitrosative posttranslational modification (PTM) regulates multiple signal transduction pathways in plants, the enzymatic systems that catalyze the reverse S-denitrosation reaction are poorly understood. This review provides an overview of the biochemistry and regulation of nitro-oxidative modifications of protein Cys residues with a focus on NO production and S-nitrosation. In addition, the importance and recent advances in defining enzymatic systems proposed to be involved in regulating S-denitrosation are addressed, specifically cytosolic thioredoxins (TRX) and the newly identified aldo-keto reductases (AKR). Full article
(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems II)
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Article
Hydrogen Sulfide Donor GYY4137 Rescues NRF2 Activation in Respiratory Syncytial Virus Infection
Antioxidants 2022, 11(7), 1410; https://doi.org/10.3390/antiox11071410 - 21 Jul 2022
Viewed by 456
Abstract
Respiratory syncytial virus (RSV) can cause severe respiratory illness in infants, immunocompromised, and older adults. Despite its burden, no vaccine or specific treatment is available. RSV infection is associated with increased reactive oxygen species (ROS) production, degradation of the transcription factor nuclear factor [...] Read more.
Respiratory syncytial virus (RSV) can cause severe respiratory illness in infants, immunocompromised, and older adults. Despite its burden, no vaccine or specific treatment is available. RSV infection is associated with increased reactive oxygen species (ROS) production, degradation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), and decreased antioxidant enzymes (AOEs), leading to oxidative damage and lung injury. Hydrogen sulfide (H2S) is an endogenous gaseous molecule that plays a physiological role in numerous cellular processes and a protective role in multiple pathological conditions, displaying vasoactive, cytoprotective, anti-inflammatory, and antioxidant activities. H2S can promote NRF2 activation through the sulfhydration of Kelch-like ECH-associated protein 1, the cytoplasmic repressor of NRF2. Here we investigated whether increasing cellular H2S levels could rescue NRF2 and NRF2-dependent gene expression in RSV-infected primary airway epithelial cells. We found that treatment with the H2S donor GYY4137 significantly increased NRF2 levels and AOEs gene expression by decreasing KEAP1 levels, and by modulating pathways involved in RSV-induced NRF2 degradation, such as NRF2 ubiquitination, and promyelocytic leukemia (PML) protein levels. These results suggest that the administration of exogenous H2S can positively impact the altered redox balance associated with RSV infection, which represents an important determinant of RSV-induced lung disease. Full article
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Article
Factors Involved in Endothelial Dysfunction Related to Angiogenic Disbalance and Oxidative Stress, in Women at High Risk of Term Pre-Eclampsia
Antioxidants 2022, 11(7), 1409; https://doi.org/10.3390/antiox11071409 - 21 Jul 2022
Viewed by 353
Abstract
Oxidative and inflammatory stress, angiogenic imbalance, and endothelial dysfunction are pathophysiological mechanisms occurring in pre-eclampsia (PE) that may persist over time and predispose women to a higher risk of cardiovascular disease (CVD) in the future. However, there is little evidence on the vascular [...] Read more.
Oxidative and inflammatory stress, angiogenic imbalance, and endothelial dysfunction are pathophysiological mechanisms occurring in pre-eclampsia (PE) that may persist over time and predispose women to a higher risk of cardiovascular disease (CVD) in the future. However, there is little evidence on the vascular function of women at risk of PE who have not developed the disease. The main objective of this research is to study factors and biomarkers involved in endothelial dysfunction related to oxidative stress, angiogenic disbalance, and inflammation in women at high risk of term PE who do not develop the disease. An observational, analytical, retrospective, and descriptive study was carried out in a selected sample of 68 high-risk and 57 non-risk of term PE participants in the STATIN study (FFIS/2016/02/ST EUDRACT No: 2016-005206-19). A significant increase in mean arterial pressure (MAP) levels and oxidative stress biomarkers (uric acid, homocysteine, and total serum antioxidant capacity) was found. Biomarkers of inflammation (interleukin-6 and growth differentiation factor 15) and endothelial function (asymmetric dimethylarginine) were significantly elevated in the group at risk of pre-eclampsia. A significative dependence relationship was also established between MAP and interleukin-6 and uric acid. These results suggest that women at high risk of term PE may represent pregnancies with pre-existing maternal risk factors for CVD, manifested by the own cardiovascular overload of pregnancy. A better understanding of maternal cardiovascular function in pregnancy would allow the improved prediction of CVD late in life in women. Full article
(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)
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Review
Role of Oxidative Stress in the Pathogenesis of Atherothrombotic Diseases
Antioxidants 2022, 11(7), 1408; https://doi.org/10.3390/antiox11071408 - 20 Jul 2022
Viewed by 463
Abstract
Oxidative stress is generated by the imbalance between reactive oxygen species (ROS) formation and antioxidant scavenger system’s activity. Increased ROS, such as superoxide anion, hydrogen peroxide, hydroxyl radical and peroxynitrite, likely contribute to the development and complications of atherosclerotic cardiovascular diseases (ASCVD). In [...] Read more.
Oxidative stress is generated by the imbalance between reactive oxygen species (ROS) formation and antioxidant scavenger system’s activity. Increased ROS, such as superoxide anion, hydrogen peroxide, hydroxyl radical and peroxynitrite, likely contribute to the development and complications of atherosclerotic cardiovascular diseases (ASCVD). In genetically modified mouse models of atherosclerosis, the overexpression of ROS-generating enzymes and uncontrolled ROS formation appear to be associated with accelerated atherosclerosis. Conversely, the overexpression of ROS scavenger systems reduces or stabilizes atherosclerotic lesions, depending on the genetic background of the mouse model. In humans, higher levels of circulating biomarkers derived from the oxidation of lipids (8-epi-prostaglandin F, and malondialdehyde), as well as proteins (oxidized low-density lipoprotein, nitrotyrosine, protein carbonyls, advanced glycation end-products), are increased in conditions of high cardiovascular risk or overt ASCVD, and some oxidation biomarkers have been reported as independent predictors of ASCVD in large observational cohorts. In animal models, antioxidant supplementation with melatonin, resveratrol, Vitamin E, stevioside, acacetin and n-polyunsaturated fatty acids reduced ROS and attenuated atherosclerotic lesions. However, in humans, evidence from large, placebo-controlled, randomized trials or prospective studies failed to show any athero-protective effect of antioxidant supplementation with different compounds in different CV settings. However, the chronic consumption of diets known to be rich in antioxidant compounds (e.g., Mediterranean and high-fish diet), has shown to reduce ASCVD over decades. Future studies are needed to fill the gap between the data and targets derived from studies in animals and their pathogenetic and therapeutic significance in human ASCVD. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in the Pathogenesis of Thrombotic Diseases)
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Article
A Dietary Antioxidant Formulation Ameliorates DNA Damage Caused by γ-Irradiation in Normal Human Bronchial Epithelial Cells In Vitro
Antioxidants 2022, 11(7), 1407; https://doi.org/10.3390/antiox11071407 - 20 Jul 2022
Viewed by 389
Abstract
Antioxidants can be used as radioprotectants to reduce DNA damage due to exposure to radiation that could result in malignancies, including lung cancer. Mortality rates are consistently higher in lung cancer, which is usually diagnosed at later stages of cancer development and progression. [...] Read more.
Antioxidants can be used as radioprotectants to reduce DNA damage due to exposure to radiation that could result in malignancies, including lung cancer. Mortality rates are consistently higher in lung cancer, which is usually diagnosed at later stages of cancer development and progression. In this preliminary study, we examined the potential of an antioxidant formulation (AOX2) to reduce DNA damage using a cell model of human normal bronchial epithelial cells (BEAS-2B). Cells were exposed to γ-irradiation or smoke-related hydrocarbon 4[(acetoxymethyl)nitrosamino]-1 (3-pyridyl) 1-butanone (NNKOAc) to induce DNA damage. We monitored intracellular reactive oxygen species (ROS) levels and evidence of genotoxic damage including DNA fragmentation ELISA, γ-H2AX immunofluorescence, and comet assays. Pre-incubation of the cells with AOX2 before exposure to γ-irradiation and NNKOAc significantly reduced DNA damage. The dietary antioxidant preparation AOX2 significantly reduced the induction of the tumor suppressor protein p53 and DNA damage-associated γ-H2AX phosphorylation by radiation and the NNKOAc treatment. Thus, AOX2 has the potential to act as a chemoprotectant by lowering ROS levels and DNA damage caused by exposure to radiation or chemical carcinogens. Full article
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Article
Oral Feeding of an Antioxidant Cocktail as a Therapeutic Strategy in a Mouse Model of Rett Syndrome: Merits and Limitations of Long-Term Treatment
Antioxidants 2022, 11(7), 1406; https://doi.org/10.3390/antiox11071406 - 20 Jul 2022
Viewed by 397
Abstract
Rett syndrome (RTT) is a severe neurodevelopmental disorder that typically arises from spontaneous germline mutations in the X-chromosomal methyl-CpG binding protein 2 (MECP2) gene. For the first 6–18 months of life, the development of the mostly female patients appears normal. Subsequently, [...] Read more.
Rett syndrome (RTT) is a severe neurodevelopmental disorder that typically arises from spontaneous germline mutations in the X-chromosomal methyl-CpG binding protein 2 (MECP2) gene. For the first 6–18 months of life, the development of the mostly female patients appears normal. Subsequently, cognitive impairment, motor disturbances, hand stereotypies, epilepsy, and irregular breathing manifest, with previously learned skills being lost. Early mitochondrial impairment and a systemic oxidative burden are part of the complex pathogenesis, and contribute to disease progression. Accordingly, partial therapeutic merits of redox-stabilizing and antioxidant (AO) treatments were reported in RTT patients and Mecp2-mutant mice. Pursuing these findings, we conducted a full preclinical trial on male and female mice to define the therapeutic value of an orally administered AO cocktail composed of vitamin E, N-acetylcysteine, and α-lipoic acid. AO treatment ameliorated some of the microcephaly-related aspects. Moreover, the reduced growth, lowered blood glucose levels, and the hippocampal synaptic plasticity of Mecp2−/y mice improved. However, the first-time detected intensified oxidative DNA damage in Mecp2-mutant cortex persisted. The behavioral performance, breathing regularity, and life expectancy of Mecp2-mutant mice did not improve upon AO treatment. Long-term-treated Mecp2+/− mice eventually became obese. In conclusion, the AO cocktail ameliorated a subset of symptoms of the complex RTT-related phenotype, thereby further confirming the potential merits of AO-based pharmacotherapies. Yet, it also became evident that long-term AO treatment may lose efficacy and even aggravate the metabolic disturbances in RTT. This emphasizes the importance of a constantly well-balanced redox balance for systemic well-being. Full article
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Article
Maqui (Aristotelia chilensis (Mol.) Stuntz): A Natural Antioxidant to Improve Quality of Meat Patties
Antioxidants 2022, 11(7), 1405; https://doi.org/10.3390/antiox11071405 - 20 Jul 2022
Viewed by 413
Abstract
Aristotelia chilensis is an endemic shrub of the South Pacific with high concentrations of bioactive compounds in its leaves and, therefore, it is highly valued. The effect of Aristotelia chilensis leaf powders (maqui leaf powders; Ma) on the quality and shelf life of [...] Read more.
Aristotelia chilensis is an endemic shrub of the South Pacific with high concentrations of bioactive compounds in its leaves and, therefore, it is highly valued. The effect of Aristotelia chilensis leaf powders (maqui leaf powders; Ma) on the quality and shelf life of beef patties during 7 days of storage was investigated. Five beef patties treatments were prepared: (1) Control without antioxidants (CT); (2) Beef patties with synthetic antioxidants plus color (250 mg/kg) (PL); (3) Beef patties with 500 ppm of maqui leaf powders (Ma500); (4) Beef patties with 1000 ppm of maqui leaf powders (Ma1000); and (5) Beef patties with 2000 ppm of maqui leaf powders (Ma2000). The quality of the beef patties was evaluated on day 0 and day 7 of storage by physicochemical analysis (moisture, ash and lipid content, color, pH, fatty acid profile and lipid oxidation) and organoleptic analysis. The addition of maqui leaf powders did not produce changes in the proximate composition of the beef patties. The pH for all treatments showed a range of 5.50–5.75 and significant differences (p < 0.05) were observed at the beginning and end of storage. The pH of the control beef patties increased during storage while the pH of the beef patties with synthetic and natural antioxidants decreased. Redness (a*) was the color indicator that was mostly affected by the inclusion of 1000 ppm and 2000 ppm powders. High lipid oxidation was observed in control samples on the seventh day of storage due to the high percentage of fat used in the formulation and the absence of any antioxidant. However, the Ma500, Ma1000, and Ma2000 treatments presented the lowest lipid oxidation rates (42.05%, 40.29%, and 43.14%, respectively) in comparison with the synthetic antioxidant (52.23%). This lipid inhibition is related to the strong antioxidant activity (29.75 µg/mL IC50 DPPH) of the maqui leaf powder due to its high content of total polyphenols (148.76 mg GAE/g), mainly characterized by having great amounts of hydroxybenzoic acids (82.5 mg GAE/g), flavonoids (7.1 mg QE/g), and hydroxycinnamic acids (3.7 mg CAE/g). Although minimal variations were observed in some individual fatty acids, and despite the trend to decrease MUFA and increase SFA with the maqui leaf powder addition, these differences were minimal and, according to the nutritional indices results, without any influence on the nutritional quality of the beef patties. The organoleptic analysis showed that the addition of maqui leaf powders did not affect the general acceptability of the new formulations. This study reports for the first time the substitution of synthetic antioxidants with Aristotelia chilensis leaves extract. Based on the results, it can be concluded that this ingredient can be used as an alternative for the production of raw meat products with clean labels. Full article
(This article belongs to the Special Issue Advances in Natural Antioxidants for Food Improvement Volume 2)
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Article
The Effect of High-Intensity Ultrasound and Natural Oils on the Extraction and Antioxidant Activity of Lycopene from Tomato (Solanum lycopersicum) Waste
Antioxidants 2022, 11(7), 1404; https://doi.org/10.3390/antiox11071404 - 20 Jul 2022
Viewed by 458
Abstract
The extraction of lycopene was carried out with three types of vegetable oils (grape, extra virgin olive, and peanut) by means of two methods: agitation and high-intensity ultrasound with a frequency of 20 kHz at an amplitude of 80% with periods of 40 [...] Read more.
The extraction of lycopene was carried out with three types of vegetable oils (grape, extra virgin olive, and peanut) by means of two methods: agitation and high-intensity ultrasound with a frequency of 20 kHz at an amplitude of 80% with periods of 40 s of sonication for 20 min at a temperature of 40 °C. The antioxidant determination by inhibition of ABTS and DPPH radicals showed no significant differences (p > 0.05) for inhibition of the ABTS radical in native oils and oils with lycopene. However, the radical DPPH showed that the native oils presented significant differences (p ≤ 0.05) compared to the samples with lycopene. FTIR spectra revealed the characteristic functional groups of lycopene exhibiting two characteristic peaks at 2923 cm−1 and 2957 cm−1. The DSC thermograms showed that the higher the degree of oil unsaturation, the lower the melting temperatures. Olive oil was the least unsaturated with the highest amount of oleic fatty acid. Grapeseed oil reported the lowest melting temperature at around −24.64 °C. Extra virgin olive oil showed the lightest values (L* = 41.08 ± 0.45) of brightness, and the peanut oil with lycopene was the darkest (L* = 16.72 ± 0.05). The extraction of lycopene from organic wastes treated with agitation and ultrasound was satisfactory reducing the use of conventional solvents. However, extraction with olive oil under agitation showed the best results. Full article
(This article belongs to the Special Issue Agri-Food Wastes as Natural Source of Bioactive Antioxidants)
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Article
Resistance to Obesity in SOD1 Deficient Mice with a High-Fat/High-Sucrose Diet
Antioxidants 2022, 11(7), 1403; https://doi.org/10.3390/antiox11071403 - 19 Jul 2022
Viewed by 444
Abstract
Metabolic syndrome (Mets) is an important condition because it may cause stroke and heart disease in the future. Reactive oxygen species (ROSs) influence the pathogenesis of Mets; however, the types of ROSs and their localization remain largely unknown. In this study, we investigated [...] Read more.
Metabolic syndrome (Mets) is an important condition because it may cause stroke and heart disease in the future. Reactive oxygen species (ROSs) influence the pathogenesis of Mets; however, the types of ROSs and their localization remain largely unknown. In this study, we investigated the effects of SOD1, which localize to the cytoplasm and mitochondrial intermembrane space and metabolize superoxide anion, on Mets using SOD1 deficient mice (SOD1−/−). SOD1−/− fed on a high-fat/high-sucrose diet (HFHSD) for 24 weeks showed reduced body weight gain and adipose tissue size compared to wild-type mice (WT). Insulin secretion was dramatically decreased in SOD1−/− fed on HFHSD even though blood glucose levels were similar to WT. Ambulatory oxygen consumption was accelerated in SOD1−/− with HFHSD; however, ATP levels of skeletal muscle were somewhat reduced compared to WT. Reflecting the reduced ATP, the expression of phosphorylated AMPK (Thr 172) was more robust in SOD1−/−. SOD1 is involved in the ATP production mechanism in mitochondria and may contribute to visceral fat accumulation by causing insulin secretion and insulin resistance. Full article
(This article belongs to the Section Antioxidant Enzyme Systems)
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Editorial
Dietary Selenium and Its Antioxidant Properties Related to Growth, Lipid and Energy Metabolism
Antioxidants 2022, 11(7), 1402; https://doi.org/10.3390/antiox11071402 - 19 Jul 2022
Viewed by 331
Abstract
Selenium (Se) is an essential trace element mainly known for its antioxidant, anti-inflammatory and anti-apoptotic properties [...] Full article
Article
Optimization of Conventional Extraction Parameters for Recovering Phenolic Compounds from Potato (Solanum tuberosum L.) Peels and Their Application as an Antioxidant in Yogurt Formulation
Antioxidants 2022, 11(7), 1401; https://doi.org/10.3390/antiox11071401 - 19 Jul 2022
Viewed by 346
Abstract
The aim of this work was to optimize the conventional parameters for the extraction of phenolic compounds from potato (Solanum tuberosum L.) peels (PP). A central composite design (CCD) was used to establish the impacts of ethanol concentration (%), extraction time (min), [...] Read more.
The aim of this work was to optimize the conventional parameters for the extraction of phenolic compounds from potato (Solanum tuberosum L.) peels (PP). A central composite design (CCD) was used to establish the impacts of ethanol concentration (%), extraction time (min), and liquid/solid ratio (mL/g). The optimal experimental conditions that maximized extraction were ethanol at a concentration of 80% (v/v) for a time of 150 min with a ratio of 1 g/30 mL. Under optimal conditions, the total phenolic content (TPC) and the total flavonoid content (TFC) were 204.41 ± 8.64 mg GAE/100 g DW and 21.47 ± 0.76 mg QE/100 g DW, respectively. The PP extract had a potent antioxidant capacity tested by phosphomolybdate and DPPH assays with IC50 of 10.65 ± 0.21 and 179.75 ± 3.18 µg/mL, respectively. Furthermore, by fortifying yogurt with PP as a natural ingredient, an improvement ofits physical, nutritional, antioxidant, and sensorial qualities was attempted in this study. The yogurts formulated with PP revealed significantly higher (p ≤ 0.05) TPC, TFC, and antioxidant capacity in comparison with the control sample. In addition, the sensory evaluation showed that the yogurts enriched with PP were preferred over the control yogurt. The results indicate that PP can be considered an interesting byproduct since it can improve the nutritional, bioactive, and sensorial profile of yogurt, highlighting that PP, due to its high phenol content, can substantially improve the antioxidant effect of the new formulated yogurt. Full article
(This article belongs to the Special Issue Antioxidant Compounds Recovered from Food Wastes)
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Article
Computation-Assisted Identification of Bioactive Compounds in Botanical Extracts: A Case Study of Anti-Inflammatory Natural Products from Hops
Antioxidants 2022, 11(7), 1400; https://doi.org/10.3390/antiox11071400 - 19 Jul 2022
Viewed by 369
Abstract
The slow pace of discovery of bioactive natural products can be attributed to the difficulty in rapidly identifying them in complex mixtures such as plant extracts. To overcome these hurdles, we explored the utility of two machine learning techniques, i.e., Elastic Net and [...] Read more.
The slow pace of discovery of bioactive natural products can be attributed to the difficulty in rapidly identifying them in complex mixtures such as plant extracts. To overcome these hurdles, we explored the utility of two machine learning techniques, i.e., Elastic Net and Random Forests, for identifying the individual anti-inflammatory principle(s) of an extract of the inflorescences of the hops (Humulus lupulus) containing hundreds of natural products. We fractionated a hop extract by column chromatography to obtain 40 impure fractions, determined their anti-inflammatory activity using a macrophage-based bioassay that measures inhibition of iNOS-mediated formation of nitric oxide, and characterized the chemical composition of the fractions by flow-injection HRAM mass spectrometry and LC-MS/MS. Among the top 10 predictors of bioactivity were prenylated flavonoids and humulones. The top Random Forests predictor of bioactivity, xanthohumol, was tested in pure form in the same bioassay to validate the predicted result (IC50 7 µM). Other predictors of bioactivity were identified by spectral similarity with known hop natural products using the Global Natural Products Social Networking (GNPS) algorithm. Our machine learning approach demonstrated that individual bioactive natural products can be identified without the need for extensive and repetitive bioassay-guided fractionation of a plant extract. Full article
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Article
Upregulation of Thioredoxin Reductase 1 Expression by Flavan-3-Ols Protects Human Kidney Proximal Tubular Cells from Hypoxia-Induced Cell Death
Antioxidants 2022, 11(7), 1399; https://doi.org/10.3390/antiox11071399 - 19 Jul 2022
Viewed by 285
Abstract
Renal hypoxia and its associated oxidative stress is a common pathway for the development of kidney diseases, and using dietary antioxidants such as flavan-3-ols to prevent kidney failure has received much attention. This study investigates the molecular mechanism by which flavan-3-ols prevent hypoxia-induced [...] Read more.
Renal hypoxia and its associated oxidative stress is a common pathway for the development of kidney diseases, and using dietary antioxidants such as flavan-3-ols to prevent kidney failure has received much attention. This study investigates the molecular mechanism by which flavan-3-ols prevent hypoxia-induced cell death in renal tubular epithelial cells. Human kidney proximal tubular cells (HKC-8) were exposed to hypoxia (1% O2) in the presence of flavan-3-ols (catechin, epicatechin, procyanidin B1, and procyanidin B2). Cell death was examined using flow cytometric analysis. Gene expression was determined using a PCR array and Western blotting, and its network and functions were investigated using STRING databases. Here, we show that the cytoprotective activity of catechin was the highest among these flavan-3-ols against hypoxia-induced cell death in cultured HKC-8 cells. Exposure of HKC-8 cells to hypoxia induced oxidative stress leading to up-regulation of DUOX2, NOX4, CYBB and PTGS2 and down-regulation of TXNRD1 and HSP90AA1. Treatment with catechin or other flavan-3-ols prevented the down-regulation of TXNRD1 expression in hypoxic HKC-8 cells. Overexpression of TXNRD1 prevented hypoxia-induced cell death, and inactivation of TXNRD1 with TRi-1, a specific TXNRD1 inhibitor, reduced the catechin cytoprotection against hypoxia-induced HKC-8 cell death. In conclusion, flavan-3-ols prevent hypoxia-induced cell death in human proximal tubular epithelial cells, which might be mediated by their maintenance of TXNRD1 expression, suggesting that enhancing TXNRD1 expression or activity may become a novel therapeutic strategy to prevent hypoxia-induced kidney damage. Full article
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Article
Loss of KEAP1 Causes an Accumulation of Nondegradative Organelles
Antioxidants 2022, 11(7), 1398; https://doi.org/10.3390/antiox11071398 - 19 Jul 2022
Viewed by 330
Abstract
KEAP1 is a cytoplasmic protein that functions as an adaptor for the Cullin-3-based ubiquitin E3 ligase system, which regulates the degradation of many proteins, including NFE2L2/NRF2 and p62/SQSTM1. Loss of KEAP1 leads to an accumulation of protein ubiquitin aggregates and defective autophagy. To [...] Read more.
KEAP1 is a cytoplasmic protein that functions as an adaptor for the Cullin-3-based ubiquitin E3 ligase system, which regulates the degradation of many proteins, including NFE2L2/NRF2 and p62/SQSTM1. Loss of KEAP1 leads to an accumulation of protein ubiquitin aggregates and defective autophagy. To better understand the role of KEAP1 in the degradation machinery, we investigated whether Keap1 deficiency affects the endosome-lysosomal pathway. We used KEAP1-deficient mouse embryonic fibroblasts (MEFs) and combined Western blot analysis and fluorescence microscopy with fluorometric and pulse chase assays to analyze the levels of lysosomal-endosomal proteins, lysosomal function, and autophagy activity. We found that the loss of keap1 downregulated the protein levels and activity of the cathepsin D enzyme. Moreover, KEAP1 deficiency caused lysosomal alterations accompanied by an accumulation of autophagosomes. Our study demonstrates that KEAP1 deficiency increases nondegradative lysosomes and identifies a new role for KEAP1 in lysosomal function that may have therapeutic implications. Full article
(This article belongs to the Special Issue Transcription Factor Nrf2)
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Review
The Role of KEAP1-NRF2 System in Atopic Dermatitis and Psoriasis
Antioxidants 2022, 11(7), 1397; https://doi.org/10.3390/antiox11071397 - 19 Jul 2022
Viewed by 409
Abstract
The Kelch-like erythroid cell-derived protein with cap‘n’collar homology-associated protein 1 (KEAP1)-nuclear factor erythroid-2-related factor 2 (NRF2) system, a thiol-based sensor-effector apparatus, exerts antioxidative and anti-inflammatory effects and maintains skin homeostasis. Thus, NRF2 activation appears to be a promising treatment option for various skin [...] Read more.
The Kelch-like erythroid cell-derived protein with cap‘n’collar homology-associated protein 1 (KEAP1)-nuclear factor erythroid-2-related factor 2 (NRF2) system, a thiol-based sensor-effector apparatus, exerts antioxidative and anti-inflammatory effects and maintains skin homeostasis. Thus, NRF2 activation appears to be a promising treatment option for various skin diseases. However, NRF2-mediated defense responses may deteriorate skin inflammation in a context-dependent manner. Atopic dermatitis (AD) and psoriasis are two common chronic inflammatory skin diseases caused by a defective skin barrier, dysregulated immune responses, genetic predispositions, and environmental factors. This review focuses on the role of the KEAP1-NRF2 system in the pathophysiology of AD and psoriasis and the therapeutic approaches that utilize this system. Full article
(This article belongs to the Special Issue Role of Oxidative Stress in the Dermatological Diseases)
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Article
Enzymatic Biosynthesis of Simple Phenolic Glycosides as Potential Anti-Melanogenic Antioxidants
Antioxidants 2022, 11(7), 1396; https://doi.org/10.3390/antiox11071396 - 19 Jul 2022
Viewed by 298
Abstract
Simple phenolics (SPs) and their glycosides have recently gained much attention as functional skin-care resources for their anti-melanogenic and antioxidant activities. Enzymatic glycosylation of SP aglycone make it feasible to create SP glycosides with updated bioactive potentials. Herein, a glycosyltransferase (GT)-encoding gene was [...] Read more.
Simple phenolics (SPs) and their glycosides have recently gained much attention as functional skin-care resources for their anti-melanogenic and antioxidant activities. Enzymatic glycosylation of SP aglycone make it feasible to create SP glycosides with updated bioactive potentials. Herein, a glycosyltransferase (GT)-encoding gene was cloned from the fosmid libraries of Streptomyces tenjimariensis ATCC 31603 using GT-specific degenerate PCR followed by in silico analyses. The recombinant StSPGT was able to flexibly catalyze the transfer of two glycosyl moieties towards two SP acceptors, (hydroxyphenyl-2-propanol [HPP2] and hydroxyphenyl-3-propanol [HPP3]), generating stereospecific α-anomeric glycosides as follows: HPP2-O-α-glucoside, HPP2-O-α-2″-deoxyglucoside, HPP3-O-α-glucoside and HPP3-O-α-2″-deoxyglucoside. This enzyme seems not only to prefer UDP-glucose and HPP2 as a favorable glycosyl donor and acceptor, respectively but also differentiates the positional difference of the hydroxyl function as acceptor catalytic sites. Paired in vitro and in vivo antioxidant assays represented SPs and their corresponding glycosides as convincing antioxidants in a time- and concentration-dependent manner by scavenging DPPH radicals and intracellular ROS. Even compared to the conventional agents, HPP2 and glycoside analogs displayed improved tyrosinase inhibitory activity in vitro and still suppressed in vivo melanogenesis. Both HPP2 glycosides are further likely to exert the best inhibitory activity against elastase, eventually highlighting these glycosides with enhanced anti-melanogenic and antioxidant activities as promising anti-wrinkle hits. Full article
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Article
Hippocampal Endoplasmic Reticulum Stress Hastens Motor and Cognitive Decline in Adult Male Rats Sustainedly Exposed to High-Sucrose Diet
Antioxidants 2022, 11(7), 1395; https://doi.org/10.3390/antiox11071395 - 19 Jul 2022
Viewed by 433
Abstract
Metabolic dysfunctions, such as hyperglycemia and insulin resistance, have been associated to cognitive impairment and dementia regardless of advanced age, although the underlying mechanisms are still elusive. Thus, this study investigates the deleterious effects of metabolic syndrome (MetS) induced by long-term exposure to [...] Read more.
Metabolic dysfunctions, such as hyperglycemia and insulin resistance, have been associated to cognitive impairment and dementia regardless of advanced age, although the underlying mechanisms are still elusive. Thus, this study investigates the deleterious effects of metabolic syndrome (MetS) induced by long-term exposure to a high-sucrose diet on motor and cognitive functions of male adult rats and its relationship with hippocampal endoplasmic reticulum (ER) stress. Weaned Wistar male rats were fed a high-sucrose diet until adulthood (HSD; 6 months old) and compared to both age-matched (CTR; 6 months old) and middle-aged chow-fed rats (OLD; 20 months old). MetS development, serum redox profile, behavioral, motor, and cognitive functions, and hippocampal gene/protein expressions for ER stress pro-adaptive and pro-apoptotic pathways, as well as senescence markers were assessed. Prolonged exposure to HSD induced MetS hallmarked by body weight gain associated to central obesity, hypertriglyceridemia, insulin resistance, and oxidative stress. Furthermore, HSD rats showed motor and cognitive decline similar to that in OLD animals. Noteworthy, HSD rats presented marked hippocampal ER stress characterized by failure of pro-adaptive signaling and increased expression of Chop, p21, and Parp-1 cleavage, markers of cell death and aging. This panorama resembles that found in OLD rats. In toto, our data showed that early and sustained exposure to a high-sucrose diet induced MetS, which subsequently led to hippocampus homeostasis disruption and premature impairment of motor and cognitive functions in adult rats. Full article
(This article belongs to the Special Issue Cross Talk between Hormones, Programming and Oxidative Stress)
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Review
Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective
Antioxidants 2022, 11(7), 1394; https://doi.org/10.3390/antiox11071394 - 19 Jul 2022
Viewed by 622
Abstract
Macrophage polarization refers to the process by which macrophages can produce two distinct functional phenotypes: M1 or M2. The balance between both strongly affects the progression of inflammatory disorders. Here, we review how redox signals regulate macrophage polarization and reprogramming during acute inflammation. [...] Read more.
Macrophage polarization refers to the process by which macrophages can produce two distinct functional phenotypes: M1 or M2. The balance between both strongly affects the progression of inflammatory disorders. Here, we review how redox signals regulate macrophage polarization and reprogramming during acute inflammation. In M1, macrophages augment NADPH oxidase isoform 2 (NOX2), inducible nitric oxide synthase (iNOS), synaptotagmin-binding cytoplasmic RNA interacting protein (SYNCRIP), and tumor necrosis factor receptor-associated factor 6 increase oxygen and nitrogen reactive species, which triggers inflammatory response, phagocytosis, and cytotoxicity. In M2, macrophages down-regulate NOX2, iNOS, SYNCRIP, and/or up-regulate arginase and superoxide dismutase type 1, counteract oxidative and nitrosative stress, and favor anti-inflammatory and tissue repair responses. M1 and M2 macrophages exhibit different metabolic profiles, which are tightly regulated by redox mechanisms. Oxidative and nitrosative stress sustain the M1 phenotype by activating glycolysis and lipid biosynthesis, but by inhibiting tricarboxylic acid cycle and oxidative phosphorylation. This metabolic profile is reversed in M2 macrophages because of changes in the redox state. Therefore, new therapies based on redox mechanisms have emerged to treat acute inflammation with positive results, which highlights the relevance of redox signaling as a master regulator of macrophage reprogramming. Full article
(This article belongs to the Special Issue Oxidative Stress, Metabolic and Inflammatory Diseases)
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Article
Investigation of the Genotoxic, Antigenotoxic and Antioxidant Profile of Different Extracts from Equisetum arvense L.
Antioxidants 2022, 11(7), 1393; https://doi.org/10.3390/antiox11071393 - 18 Jul 2022
Viewed by 347
Abstract
The present study investigated the cyto-genotoxic and antigenotoxic effects of four different extracts of Equisetum arvense L. (common name: field horsetail) on human lymphocytes. Specifically, Soxhlet’s prepared extracts from E. arvense L., using different solvents (S1: methanol (MeOH)-, S2: ethanol (EtOH)-, S3: water-, [...] Read more.
The present study investigated the cyto-genotoxic and antigenotoxic effects of four different extracts of Equisetum arvense L. (common name: field horsetail) on human lymphocytes. Specifically, Soxhlet’s prepared extracts from E. arvense L., using different solvents (S1: methanol (MeOH)-, S2: ethanol (EtOH)-, S3: water-, and S4: ethanol/water (EtOH-W)-) were analyzed for (a) their total phenolic and flavonoid content (TPC and TFC, respectively), (b) their antioxidant activity (AA), via the DPPH, FRAP and ABTS assays, and (c) their cyto-genotoxic and/or protective efficiency against the mutagenic agent mitomycin C, via the Cytokinesis Block MicroNucleus assay. All extracts showed increased TPC, TFC, and AA values in almost all cases. S1, S3 and S4 demonstrated no cytotoxic potential, whereas S2 was cytotoxic only at the highest concentrations. Genotoxicity was not observed in the tested extracts. The highest antigenotoxic activity was observed for EtOH-W (S4) extract, which was found to be rich in flavonoids, flavonoid-O-glycosides, phytosterols, phenolic and fatty acids as well as in minerals and mainly in K, Ca, Mg, Si and P, as assessed by using various mass spectrometry techniques. Those findings confirm that E. arvense L. extracts could be valuable candidates for medicinal applications and pharmaceutical products, thus alleviating the effects of more conventional drugs. Full article
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Article
Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell Lines
Antioxidants 2022, 11(7), 1392; https://doi.org/10.3390/antiox11071392 - 18 Jul 2022
Viewed by 399
Abstract
Paeonol is a naturally occurring phenolic agent that attenuates neurotoxicity in neurodegenerative diseases. We aimed to investigate the antioxidant and protective effects of paeonol and determine its transport mechanism in wild-type (WT; NSC-34/hSOD1WT) and mutant-type (MT; NSC-34/hSOD1G93A) motor neuron-like [...] Read more.
Paeonol is a naturally occurring phenolic agent that attenuates neurotoxicity in neurodegenerative diseases. We aimed to investigate the antioxidant and protective effects of paeonol and determine its transport mechanism in wild-type (WT; NSC-34/hSOD1WT) and mutant-type (MT; NSC-34/hSOD1G93A) motor neuron-like amyotrophic lateral sclerosis (ALS) cell lines. Cytotoxicity induced by glutamate, lipopolysaccharides, and H2O2 reduced viability of cell; however, the addition of paeonol improved cell viability against neurotoxicity. The [3H]paeonol uptake was increased in the presence of H2O2 in both cell lines. Paeonol recovered ALS model cell lines by reducing mitochondrial oxidative stress induced by glutamate. The transport of paeonol was time-, concentration-, and pH-dependent in both NSC-34 cell lines. Kinetic parameters showed two transport sites with altered affinity and capacity in the MT cell line compared to the WT cell line. [3H]Paeonol uptake increased in the MT cell line transfected with organic anion transporter1 (Oat1)/Slc22a6 small interfering RNA compared to that in the control. Plasma membrane monoamine transporter (Pmat) was also involved in the uptake of paeonol by ALS model cell lines. Overall, paeonol exhibits neuroprotective activity via a carrier-mediated transport system and may be a beneficial therapy for preventing motor neuronal damage under ALS-like conditions. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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Article
Taurine Attenuates Oxidized Fish Oil-Induced Oxidative Stress and Lipid Metabolism Disorder in Mice
Antioxidants 2022, 11(7), 1391; https://doi.org/10.3390/antiox11071391 - 18 Jul 2022
Viewed by 489
Abstract
The objective of this study was to determine the effect of dietary taurine on lipid metabolism and liver injury in mice fed a diet high in oxidized fish oil. The ICR mice (six weeks old) were randomly assigned to six groups and fed [...] Read more.
The objective of this study was to determine the effect of dietary taurine on lipid metabolism and liver injury in mice fed a diet high in oxidized fish oil. The ICR mice (six weeks old) were randomly assigned to six groups and fed different diets for 10 weeks: control (CON), normal plus 15% fresh fish oil diet (FFO), normal plus 15% oxidized fish oil diet (OFO), or OFO plus 0.6% (TAU1), 0.9% (TAU2) or 1.2% (TAU3) taurine. Compared to the CON group, OFO mice showed increased liver index, aspartate aminotransferase (AST) and malondialdehyde (MDA) levels in serum (p < 0.05). In addition, OFO mice had increased cholesterol (CHOL)/high-density lipoprotein cholesterol (HDL-C) and decreased HDL-C/low-density lipoprotein cholesterol (LDL-C) and n-6/n-3 polyunsaturated fatty acid (PUFA) ratio in serum (p < 0.05) compared with CON mice. Notably, dietary taurine ameliorated the liver index and AST and MDA levels in serum and liver in a more dose-dependent manner than OFO mice. In addition, compared to OFO mice, decreased levels of CHOL and ratio of CHOL/HDL-C and n-6 PUFA/n-3 PUFA in serum were found in TAU3-fed mice. Supplementation with TAU2 and TAU3 increased the relative mRNA expression levels of peroxisome proliferator-activated receptor α, adipose triglyceride lipase, lipoprotein lipase, hormone-sensitive lipase and carnitine palmitoyl transferase 1 in liver compared with the OFO group (p < 0.05). Moreover, impaired autophagy flux was detected in mice fed with the OFO diet, and this was prevented by taurine. These findings suggested that dietary taurine might provide a potential therapeutic choice against oxidative stress and lipid metabolism disorder. Full article
(This article belongs to the Special Issue Oxidative Stress, Reactive Oxygen Species and Animal Nutrition)
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Article
Rhodomyrtus tomentosa Fruits in Two Ripening Stages: Chemical Compositions, Antioxidant Capacity and Digestive Enzymes Inhibitory Activity
Antioxidants 2022, 11(7), 1390; https://doi.org/10.3390/antiox11071390 - 18 Jul 2022
Viewed by 307
Abstract
Rhodomyrtus tomentosa fruit (RTF) has been known as a food source with multiple health-care components. In this work, nutrition characteristics, free and bound phenolic profiles, antioxidant properties in vitro and digestive enzymes inhibitory activities of un-fully mature RTF (UM-RTF) and fully mature RTF [...] Read more.
Rhodomyrtus tomentosa fruit (RTF) has been known as a food source with multiple health-care components. In this work, nutrition characteristics, free and bound phenolic profiles, antioxidant properties in vitro and digestive enzymes inhibitory activities of un-fully mature RTF (UM-RTF) and fully mature RTF (FM-RTF) were evaluated for the first time. Results verified that high levels of energy, ascorbic acid, organic acids and total phenolics were observed in FM-RTF. Moreover, FM-RTF had significant higher total phenolic content (TPC), but significantly lower total flavonoid content (TFC) than UM-RTF. In addition, twenty phenolic compounds in RTF were identified by high performance liquid chromatography–electrospray ionization–quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-qTOF-MS/MS) method. Quantitative analysis results indicated that gallic acid, ellagic acid and astragalin were the predominant free phenolics, while gallic acid and syringetin-3-O-glucoside were dominant in bound phenolic fractions. In contrast, higher contents of phenolics were observed in FM-RTF. The results also confirmed that FM-RTF exhibited higher antioxidant activities and digestive enzymes inhibitory activities than UM-RTF. Strong inhibitory ability on α-glucosidase was found in RTF, while bound phenolics showed a stronger α-amylase inhibitory effect than free phenolics. Moreover, the interaction between the main phenolic compounds and α-glucosidase/α-amylase was preliminary explored by molecular docking analysis. The results provided valuable data about the chemical compositions and biological potential of R. tomentosa fruits in both maturation stages studied. Full article
(This article belongs to the Special Issue Antioxidant Potential of Extracts from Foods and Plants)
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Article
In Vitro Efficacy and Molecular Mechanism of Curcumin Analog in Pathological Regulation of Spinocerebellar Ataxia Type 3
Antioxidants 2022, 11(7), 1389; https://doi.org/10.3390/antiox11071389 - 18 Jul 2022
Viewed by 348
Abstract
Unlike other nuclear factor erythroid-2-related factor 2 (Nrf2) activators, the mechanism of action of curcumin analog, ASC-JM17 (JM17), in regulating oxidative homeostasis remains unknown. Spinocerebellar ataxia type 3 (SCA3) is an inherited polyglutamine neurodegenerative disease caused mainly by polyglutamine neurotoxicity and oxidative stress. [...] Read more.
Unlike other nuclear factor erythroid-2-related factor 2 (Nrf2) activators, the mechanism of action of curcumin analog, ASC-JM17 (JM17), in regulating oxidative homeostasis remains unknown. Spinocerebellar ataxia type 3 (SCA3) is an inherited polyglutamine neurodegenerative disease caused mainly by polyglutamine neurotoxicity and oxidative stress. Presently, we compared actions of JM17 with those of known Nrf2 activators, omaveloxolone (RTA-408) and dimethyl fumarate (DMF), using human neuroblastoma SK-N-SH cells with stable transfection of full-length ataxin-3 protein with 78 CAG repeats (MJD78) to clarify the resulting pathological mechanism by assaying mitochondrial function, mutant ataxin-3 protein toxicity, and oxidative stress. JM17, 1 μM, comprehensively restored mitochondrial function, decreased mutant protein aggregates, and attenuated intracellular/mitochondrial reactive oxygen species (ROS) levels. Although JM17 induced dose-dependent Nrf2 activation, a low dose of JM17 (less than 5 μM) still had a better antioxidant ability compared to the other Nrf2 activators and specifically increased mitochondrial superoxide dismutase 2 in an Nrf2-dependent manner as shown by knockdown experiments with siRNA. It showed that activation of Nrf2 in response to ROS generated in mitochondria could play an import role in the benefit of JM17. This study presents the diversified regulation of JM17 in a pathological process and helped develop more effective therapeutic strategies for SCA3. Full article
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