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Antioxidants, Volume 9, Issue 10 (October 2020) – 124 articles

Cover Story (view full-size image): Cancer has become the second leading cause of death worldwide. Despite the advances of early diagnosis and anticancer therapies, cancer rates are expected to rise further. As such, cancer prevention continues to play an important role in cancer control. Among the hallmarks of cancer, maintenance of genomic integrity is crucial for cancer prevention and plays a role in mitigating the effects of oxidative stress. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is the key cell signaling mechanism that responds to oxidative stress to maintain redox homeostasis and thus counteract the deleterious effects of free radicals that can damage DNA. In this review paper, we discuss the role of dietary flavonoids on regulation of the Nrf2/ARE pathway in relation to cancer prevention and management. View this paper
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14 pages, 1667 KiB  
Article
Effects of Selenium- and Zinc-Enriched Lactobacillus plantarum SeZi on Antioxidant Capacities and Gut Microbiome in an ICR Mouse Model
by Sini Kang, Rui Li, Hui Jin, Hyun Ju You and Geun Eog Ji
Antioxidants 2020, 9(10), 1028; https://doi.org/10.3390/antiox9101028 - 21 Oct 2020
Cited by 15 | Viewed by 3815
Abstract
Selenium and zinc are essential trace minerals for humans with various biological functions. In this study, selenium- and zinc-tolerant lactic acid bacteria (LAB) isolates were screened out from human fecal samples. Amongst three hundred LAB isolates, the Lactobacillus plantarum SeZi strain displayed the [...] Read more.
Selenium and zinc are essential trace minerals for humans with various biological functions. In this study, selenium- and zinc-tolerant lactic acid bacteria (LAB) isolates were screened out from human fecal samples. Amongst three hundred LAB isolates, the Lactobacillus plantarum SeZi strain displayed the tolerance against selenium and zinc with the greatest biomass production and bioaccumulation of selenium and zinc. To further assess the characteristics of this strain, the lyophilized L. plantarum SeZi were prepared and administered to Institute of Cancer Research (ICR) mice. The mice were divided into four groups, provided with normal chow (Con), or normal chow supplemented with Na2SeO3 and ZnSO4∙7H2O (SZ), L. plantarum SeZi (Lp), or selenium- and zinc-enriched L. plantarum SeZi (SZ + Lp), respectively. After 4 weeks of oral administration, the concentrations of selenium and zinc in blood were significantly increased in the SZ + Lp group when compared to the control or SZ group (p < 0.05). The increased selenium level led to an enhanced glutathione peroxidase activity and decreased blood malondialdehyde level in the SZ + Lp group (p < 0.05). Meanwhile, the results of bacterial community and microbial metabolic pathway analysis via 16S rRNA gene amplicon sequencing showed that L. plantarum SeZi significantly promoted the utilization of selenocysteine, seleno-cystathionine and seleno-methionine in the selenocompounds metabolism. Here, the in vivo antioxidant capacities of the selenium- and zinc-enriched lactobacillus strain showed us the utilization of a unique probiotic as a Se/Zn supplement with high availability, low toxicity, and additional probiotic advantages. Full article
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29 pages, 4758 KiB  
Article
Chemico-Biological Characterization of Torpedino Di Fondi® Tomato Fruits: A Comparison with San Marzano Cultivar at Two Ripeness Stages
by Cinzia Ingallina, Alessandro Maccelli, Mattia Spano, Giacomo Di Matteo, Antonella Di Sotto, Anna Maria Giusti, Giuliana Vinci, Silvia Di Giacomo, Mattia Rapa, Salvatore Ciano, Caterina Fraschetti, Antonello Filippi, Giovanna Simonetti, Carlos Cordeiro, Marta Sousa Silva, Maria Elisa Crestoni, Anatoly P. Sobolev, Simonetta Fornarini and Luisa Mannina
Antioxidants 2020, 9(10), 1027; https://doi.org/10.3390/antiox9101027 - 21 Oct 2020
Cited by 11 | Viewed by 2986
Abstract
Torpedino di Fondi (TF) is a hybrid tomato landrace developed in Sicily and recently introduced in the south Lazio area along with the classical San Marzano (SM) cultivar. The present study aimed at characterizing TF tomatoes at both pink and red ripening stages, [...] Read more.
Torpedino di Fondi (TF) is a hybrid tomato landrace developed in Sicily and recently introduced in the south Lazio area along with the classical San Marzano (SM) cultivar. The present study aimed at characterizing TF tomatoes at both pink and red ripening stages, and at comparing them with traditional SM tomatoes. A multidisciplinary approach consisting of morphological, chemical (FT-ICR MS, NMR, HPLC, and spectrophotometric methods), and biological (antioxidant and antifungal in vitro activity) analyses was applied. Morphological analysis confirmed the mini-San Marzano nature and the peculiar crunchy and solid consistency of TF fruits. Pink TF tomatoes displayed the highest content of hydrophilic antioxidants, like total polyphenols (0.192 mg/g), tannins (0.013 mg/g), flavonoids (0.204 mg/g), and chlorophylls a (0.344 mg/g) and b (0.161 mg/g), whereas red TF fruits were characterized by the highest levels of fructose (3000 mg/100 g), glucose (2000 mg/100 g), tryptophan (2.7 mg/100 g), phenylalanine (13 mg/100 g), alanine (25 mg/100 g), and total tri-unsaturated fatty acids (13% mol). Red SM fruits revealed the greatest content of lipophilic antioxidants, with 1234 mg/g of total carotenoids. In agreement with phenolics content, TF cultivar showed the greatest antioxidant activity. Lastly, red TF inhibited Candida species (albicans, glabrata and krusei) growth. Full article
(This article belongs to the Special Issue The Potential of Dietary Antioxidants)
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18 pages, 23405 KiB  
Article
CDDO-Me Distinctly Regulates Regional Specific Astroglial Responses to Status Epilepticus via ERK1/2-Nrf2, PTEN-PI3K-AKT and NFκB Signaling Pathways
by Ji-Eun Kim, Hana Park and Tae-Cheon Kang
Antioxidants 2020, 9(10), 1026; https://doi.org/10.3390/antiox9101026 - 21 Oct 2020
Cited by 9 | Viewed by 2554
Abstract
2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid. CDDO-Me shows anti-inflammatory and neuroprotective effects. Furthermore, CDDO-Me has antioxidant properties, since it activates nuclear factor-erythroid 2-related factor 2 (Nrf2), which is a key player of redox homeostasis. In the present [...] Read more.
2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid. CDDO-Me shows anti-inflammatory and neuroprotective effects. Furthermore, CDDO-Me has antioxidant properties, since it activates nuclear factor-erythroid 2-related factor 2 (Nrf2), which is a key player of redox homeostasis. In the present study, we evaluated whether CDDO-Me affects astroglial responses to status epilepticus (SE, a prolonged seizure activity) in the rat hippocampus in order to understand the underlying mechanisms of reactive astrogliosis and astroglial apoptosis. Under physiological conditions, CDDO-Me increased Nrf2 expression in the hippocampus without altering activities (phosphorylations) of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphatidylinositol-3-kinase (PI3K), and AKT. CDDO-Me did not affect seizure activity in response to pilocarpine. However, CDDO-Me ameliorated reduced astroglial Nrf2 expression in the CA1 region and the molecular layer of the dentate gyrus (ML), and attenuated reactive astrogliosis and ML astroglial apoptosis following SE. In CA1 astrocytes, CDDO-Me inhibited the PI3K/AKT pathway by activating PTEN. In contrast, CDDO-ME resulted in extracellular signal-related kinases 1/2 (ERK1/2)-mediated Nrf2 upregulation in ML astrocytes. Furthermore, CDDO-Me decreased nuclear factor-κB (NFκB) phosphorylation in both CA1 and ML astrocytes. Therefore, our findings suggest that CDDO-Me may attenuate SE-induced reactive astrogliosis and astroglial apoptosis via regulation of ERK1/2-Nrf2, PTEN-PI3K-AKT, and NFκB signaling pathways. Full article
(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Disorders)
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15 pages, 2784 KiB  
Article
Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3
by Lara Ibrahim, Jaleh Mesgarzadeh, Ian Xu, Evan T. Powers, R. Luke Wiseman and Michael J. Bollong
Antioxidants 2020, 9(10), 1025; https://doi.org/10.3390/antiox9101025 - 21 Oct 2020
Cited by 26 | Viewed by 4817
Abstract
The NRF transcription factors NRF1, NRF2, and NRF3, are a subset of Cap‘n’collar transcriptional regulators which modulate the expression of genes harboring antioxidant-response element (ARE) sequences within their genomic loci. Despite the emerging physiological importance of NRF family members, the repertoire of their [...] Read more.
The NRF transcription factors NRF1, NRF2, and NRF3, are a subset of Cap‘n’collar transcriptional regulators which modulate the expression of genes harboring antioxidant-response element (ARE) sequences within their genomic loci. Despite the emerging physiological importance of NRF family members, the repertoire of their genetic targets remains incompletely defined. Here we use RNA-sequencing-based transcriptional profiling and quantitative proteomics to delineate the overlapping and differential genetic programs effected by the three NRF transcription factors. We then create consensus target gene sets regulated by NRF1, NRF2, and NRF3 and define the integrity of these gene sets for probing NRF activity in mammalian cell culture and human tissues. Together, our data provide a quantitative assessment of how NRF family members sculpt proteomes and transcriptomes, providing a framework to understand the critical physiological importance of NRF transcription factors and to establish pharmacologic approaches for therapeutically activating these transcriptional programs in disease. Full article
(This article belongs to the Special Issue Keap1/Nrf2 Signaling Pathway)
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15 pages, 963 KiB  
Article
Betaine and Isoquinoline Alkaloids Protect against Heat Stress and Colonic Permeability in Growing Pigs
by Hieu Huu Le, Majid Shakeri, Hafiz Ansar Rasul Suleria, Weicheng Zhao, Rachel Mai McQuade, Deborah Jayne Phillips, Eva Vidacs, John Barton Furness, Frank Rowland Dunshea, Valeria Artuso-Ponte and Jeremy James Cottrell
Antioxidants 2020, 9(10), 1024; https://doi.org/10.3390/antiox9101024 - 21 Oct 2020
Cited by 18 | Viewed by 4284
Abstract
Heat stress (HS) compromises productivity of pork production, in part as a result of increased oxidative stress and inflammatory responses, particularly within the gastrointestinal tract. This study aimed to investigate whether plant-derived betaine and isoquinoline alkaloids could ameliorate HS in pigs. Fifty female [...] Read more.
Heat stress (HS) compromises productivity of pork production, in part as a result of increased oxidative stress and inflammatory responses, particularly within the gastrointestinal tract. This study aimed to investigate whether plant-derived betaine and isoquinoline alkaloids could ameliorate HS in pigs. Fifty female Large White × Landrace grower pigs, which were acclimated to control (CON), control plus betaine (BET), or control plus isoquinoline alkaloids (IQA) diets for 14 days were then exposed to heat stress or thermoneutral condition. Both BET and IQA partially ameliorated increases in respiration rate (p = 0.013) and rectal temperature (p = 0.001) associated with HS conditions. Heat stress increased salivary cortisol concentrations and reduced plasma creatinine, lactate, and thyroid hormone concentrations. Heat stress increased colon FD4 permeability, which was reduced by IQA (p = 0.030). Heat stress increased inflammation in the jejunum and ileum, as indicated by elevated interleukin-1β (p = 0.022) in the jejunum and interleukin-1β (p = 0.004) and interleukin-8 (p = 0.001) in the ileum. No differences in plasma total antioxidant capacity (TAC) were observed with HS, but betaine increased plasma TAC compared to IQA. Dietary BET increased betaine concentrations in the jejunum, ileum (p < 0.001 for both), plasma, liver, kidney (p < 0.010 for all), urine (p = 0.002) and tended to be higher in muscle (p = 0.084). Betaine concentration was not influenced by HS, but it tended to be higher in plasma and accumulated in the liver. These data suggest that betaine and isoquinoline alkaloids supplementation ameliorated consequences of heat stress in grower pigs and protected against HS induced increases in colonic permeability. Full article
(This article belongs to the Special Issue Antioxidants in Veterinary Medicine)
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30 pages, 1049 KiB  
Review
Polyphenols in Farm Animals: Source of Reproductive Gain or Waste?
by Nesrein M. Hashem, Antonio Gonzalez-Bulnes and Jesus Simal-Gandara
Antioxidants 2020, 9(10), 1023; https://doi.org/10.3390/antiox9101023 - 21 Oct 2020
Cited by 36 | Viewed by 4878
Abstract
Reproduction is a complex process that is substantially affected by environmental cues, specifically feed/diet and its components. Farm animals as herbivorous animals are exposed to a large amount of polyphenols present in their natural feeding system, in alternative feed resources (shrubs, trees, and [...] Read more.
Reproduction is a complex process that is substantially affected by environmental cues, specifically feed/diet and its components. Farm animals as herbivorous animals are exposed to a large amount of polyphenols present in their natural feeding system, in alternative feed resources (shrubs, trees, and agro-industrial byproducts), and in polyphenol-enriched additives. Such exposure has increased because of the well-known antioxidant properties of polyphenols. However, to date, the argumentation around the impacts of polyphenols on reproductive events is debatable. Accordingly, the intensive inclusion of polyphenols in the diets of breeding animals and in media for assisted reproductive techniques needs further investigation, avoiding any source of reproductive waste and achieving maximum benefits. This review illustrates recent findings connecting dietary polyphenols consumption from different sources (conventional and unconventional feeds) with the reproductive performance of farm animals, underpinned by the findings of in vitro studies in this field. This update will help in formulating proper diets, optimizing the introduction of new plant species, and feed additives for improving reproductive function, avoiding possible reproductive wastes and maximizing possible benefits. Full article
(This article belongs to the Special Issue Antioxidants in Veterinary Medicine)
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34 pages, 2571 KiB  
Review
Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation
by Fiona Limanaqi, Francesca Biagioni, Federica Mastroiacovo, Maico Polzella, Gloria Lazzeri and Francesco Fornai
Antioxidants 2020, 9(10), 1022; https://doi.org/10.3390/antiox9101022 - 20 Oct 2020
Cited by 32 | Viewed by 5553
Abstract
Wide experimental evidence has been provided in the last decade concerning the neuroprotective effects of phytochemicals in a variety of neurodegenerative disorders. Generally, the neuroprotective effects of bioactive compounds belonging to different phytochemical classes are attributed to antioxidant, anti-aggregation, and anti-inflammatory activity along [...] Read more.
Wide experimental evidence has been provided in the last decade concerning the neuroprotective effects of phytochemicals in a variety of neurodegenerative disorders. Generally, the neuroprotective effects of bioactive compounds belonging to different phytochemical classes are attributed to antioxidant, anti-aggregation, and anti-inflammatory activity along with the restoration of mitochondrial homeostasis and targeting alterations of cell-clearing systems. Far from being independent, these multi-target effects represent interconnected events that are commonly implicated in the pathogenesis of most neurodegenerative diseases, independently of etiology, nosography, and the specific misfolded proteins being involved. Nonetheless, the increasing amount of data applying to a variety of neurodegenerative disorders joined with the multiple effects exerted by the wide variety of plant-derived neuroprotective agents may rather confound the reader. The present review is an attempt to provide a general guideline about the most relevant mechanisms through which naturally occurring agents may counteract neurodegeneration. With such an aim, we focus on some popular phytochemical classes and bioactive compounds as representative examples to design a sort of main highway aimed at deciphering the most relevant protective mechanisms which make phytochemicals potentially useful in counteracting neurodegeneration. In this frame, we emphasize the potential role of the cell-clearing machinery as a kernel in the antioxidant, anti-aggregation, anti-inflammatory, and mitochondrial protecting effects of phytochemicals. Full article
(This article belongs to the Special Issue Role of Natural Antioxidants on Neuroprotection and Neuroinflammation)
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18 pages, 3306 KiB  
Article
The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses
by Ho-Jae Lee, Joon Seok Park, Hyun Jung Yoo, Hae Min Lee, Byung Cheon Lee and Ji Hyung Kim
Antioxidants 2020, 9(10), 1021; https://doi.org/10.3390/antiox9101021 - 20 Oct 2020
Cited by 14 | Viewed by 3641
Abstract
Immune activation associates with the intracellular generation of reactive oxygen species (ROS). To elicit effective immune responses, ROS levels must be balanced. Emerging evidence shows that ROS-mediated signal transduction can be regulated by selenoproteins such as methionine sulfoxide reductase B1 (MsrB1). However, how [...] Read more.
Immune activation associates with the intracellular generation of reactive oxygen species (ROS). To elicit effective immune responses, ROS levels must be balanced. Emerging evidence shows that ROS-mediated signal transduction can be regulated by selenoproteins such as methionine sulfoxide reductase B1 (MsrB1). However, how the selenoprotein shapes immunity remains poorly understood. Here, we demonstrated that MsrB1 plays a crucial role in the ability of dendritic cells (DCs) to provide the antigen presentation and costimulation that are needed for cluster of differentiation antigen four (CD4) T-cell priming in mice. We found that MsrB1 regulated signal transducer and activator of transcription-6 (STAT6) phosphorylation in DCs. Moreover, both in vitro and in vivo, MsrB1 potentiated the lipopolysaccharide (LPS)-induced Interleukin-12 (IL-12) production by DCs and drove T-helper 1 (Th1) differentiation after immunization. We propose that MsrB1 activates the STAT6 pathway in DCs, thereby inducing the DC maturation and IL-12 production that promotes Th1 differentiation. Additionally, we showed that MsrB1 promoted follicular helper T-cell (Tfh) differentiation when mice were immunized with sheep red blood cells. This study unveils as yet unappreciated roles of the MsrB1 selenoprotein in the innate control of adaptive immunity. Targeting MsrB1 may have therapeutic potential in terms of controlling immune reactions. Full article
(This article belongs to the Special Issue Biological Significance of Methionine Oxidation and Reduction)
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28 pages, 908 KiB  
Review
Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)
by Isabel Hinarejos, Candela Machuca, Paula Sancho and Carmen Espinós
Antioxidants 2020, 9(10), 1020; https://doi.org/10.3390/antiox9101020 - 20 Oct 2020
Cited by 40 | Viewed by 7408
Abstract
The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are [...] Read more.
The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA genes. In line with this, isolated cases of known monogenic disorders, and also, new genetic diseases, which present with abnormal brain iron phenotypes compatible with NBIA, have been described. Several pathways are involved in NBIA syndromes: iron and lipid metabolism, mitochondrial dynamics, and autophagy. However, many neurodegenerative conditions share features such as mitochondrial dysfunction and oxidative stress, given the bioenergetics requirements of neurons. This review aims to describe the existing link between the classical ten NBIA forms by examining their connection with mitochondrial impairment as well as oxidative stress and neuroinflammation. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Health and Diseases)
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41 pages, 942 KiB  
Review
A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases
by Nur Zuliani Ramli, Mohamad Fairuz Yahaya, Ikuo Tooyama and Hanafi Ahmad Damanhuri
Antioxidants 2020, 9(10), 1019; https://doi.org/10.3390/antiox9101019 - 20 Oct 2020
Cited by 20 | Viewed by 4203
Abstract
Nutraceuticals have been extensively studied worldwide due to its neuroprotective effects in in vivo and in vitro studies, attributed by the antioxidative properties. Alzheimer (AD) and Parkinson disease (PD) are the two main neurodegenerative disorders that are discussed in this review. Both AD [...] Read more.
Nutraceuticals have been extensively studied worldwide due to its neuroprotective effects in in vivo and in vitro studies, attributed by the antioxidative properties. Alzheimer (AD) and Parkinson disease (PD) are the two main neurodegenerative disorders that are discussed in this review. Both AD and PD share the similar involvement of oxidative stress in their pathophysiology. Nutraceuticals exert their antioxidative effects via direct scavenging of free radicals, prevent damage to biomolecules, indirectly stimulate the endogenous antioxidative enzymes and gene expressions, inhibit activation of pro-oxidant enzymes, and chelate metals. In addition, nutraceuticals can act as modulators of pro-survival, pro-apoptotic, and inflammatory signaling pathways. They have been shown to be effective particularly in preclinical stages, due to their multiple mechanisms of action in attenuating oxidative stress underlying AD and PD. Natural antioxidants from food sources and natural products such as resveratrol, curcumin, green tea polyphenols, and vitamin E are promising therapeutic agents in oxidative stress-mediated neurodegenerative disease as they have fewer adverse effects, more tolerable, cheaper, and sustainable for long term consumption. Full article
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21 pages, 616 KiB  
Review
Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain
by Caitlyn A. Mullins, Ritchel B. Gannaban, Md Shahjalal Khan, Harsh Shah, Md Abu B. Siddik, Vijay K. Hegde, P. Hemachandra Reddy and Andrew C. Shin
Antioxidants 2020, 9(10), 1018; https://doi.org/10.3390/antiox9101018 - 20 Oct 2020
Cited by 29 | Viewed by 4345
Abstract
Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in [...] Read more.
Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed. Full article
(This article belongs to the Special Issue Oxidative Stress in Obesity)
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17 pages, 1758 KiB  
Review
Anthocyanins from Purple Tomatoes as Novel Antioxidants to Promote Human Health
by Silvia Gonzali and Pierdomenico Perata
Antioxidants 2020, 9(10), 1017; https://doi.org/10.3390/antiox9101017 - 20 Oct 2020
Cited by 31 | Viewed by 6106
Abstract
Anthocyanins are plant secondary metabolites belonging to the class of polyphenols, whose beneficial roles in the prevention and treatment of several important human diseases have been demonstrated in many epidemiological studies. Their intake through diet strictly depends on the eating habits, as anthocyanins [...] Read more.
Anthocyanins are plant secondary metabolites belonging to the class of polyphenols, whose beneficial roles in the prevention and treatment of several important human diseases have been demonstrated in many epidemiological studies. Their intake through diet strictly depends on the eating habits, as anthocyanins are contained in red and purple fruit and vegetables as well as in some processed foods and beverages, such as red wine. Genetic engineering and breeding programs have been recently carried out to increase the content of anthocyanins in candidate plant species which cannot offer satisfactory levels of these precious compounds. Tomato (Solanum lycopersicum) is a vegetable commodity where these strategies have resulted in success, leading to the production of new anthocyanin-rich fruit varieties, some of which are already marketed. These varieties produce purple fruits with a high nutraceutical value, combining the health benefits of the anthocyanins to the other classical tomato phytochemicals, particularly carotenoids. The antioxidant capacity in tomato purple fruits is higher than in non-anthocyanin tomatoes and their healthy role has already been demonstrated in both in vitro and in vivo studies. Recent evidence has indicated a particular capacity of tomato fruit anthocyanins to act as scavengers of harmful reactive chemical species and inhibitors of proliferating cancer cells, as well as anti-inflammatory molecules. Full article
(This article belongs to the Special Issue Plant Antioxidants in the “One Health” Paradigm)
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15 pages, 1641 KiB  
Article
Changes in Bioactive Compounds, Antioxidant Activity, and Nutritional Quality of Blood Orange Cultivars at Different Storage Temperatures
by Fariborz Habibi, Asghar Ramezanian, Fabián Guillén, Salvador Castillo, María Serrano and Daniel Valero
Antioxidants 2020, 9(10), 1016; https://doi.org/10.3390/antiox9101016 - 20 Oct 2020
Cited by 41 | Viewed by 4314
Abstract
Information about the postharvest physiological behavior of blood orange cultivars can provide comprehensive insight into the best period of storage to maintain the highest fruit quality during prolonged cold storage. In this paper, changes in nutritional quality, bioactive compounds, and antioxidant enzymes in [...] Read more.
Information about the postharvest physiological behavior of blood orange cultivars can provide comprehensive insight into the best period of storage to maintain the highest fruit quality during prolonged cold storage. In this paper, changes in nutritional quality, bioactive compounds, and antioxidant enzymes in the juice of four blood orange cultivars (“Moro”, “Tarocco”, “Sanguinello”, and “Sanguine”) stored at 2 and 5 °C were studied. Parameters were measured after 0, 30, 60, 90, 120, 150, and 180 days, plus 2 days at 20 °C for shelf life. Sucrose was the sugar found in higher concentrations and decreased during storage in all cultivars, as did glucose and fructose. Organic acids decreased at both temperatures, with the highest content found in “Sanguinello”, especially major (citric acid) and ascorbic acid. Total phenolics content (TPC), total anthocyanins (TAC), and individual cyanidin 3-glucoside and cyanidin 3-(6″-malonylglucoside) increased for all cultivars, with “Sanguinello” having higher concentrations. The antioxidant enzymes catalase (CAT), ascorbate peroxidase (APX), and superoxide dismutase (SOD) were also higher in “Sanguinello” and increased during storage. Overall, these results together with the sensory analysis suggested that “Sanguinello” would be the best cultivar for prolonged storage. The results of this study could be useful to select the best storage duration and temperature for each cultivar and provide the presence of such a high-value commodity for fresh consumption or juice processing long after the harvest season. Full article
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14 pages, 3424 KiB  
Article
Chemometric Analysis of Extracts and Fractions from Green, Oxidized, and Microbial Fermented Teas and Their Correlation to Potential Antioxidant and Anticancer Effects
by Chan-Su Rha, Young Sung Jung, Jung-Dae Lee, Davin Jang, Mi-Seon Kim, Min-Seuk Lee, Yong Deok Hong and Dae-Ok Kim
Antioxidants 2020, 9(10), 1015; https://doi.org/10.3390/antiox9101015 - 19 Oct 2020
Cited by 12 | Viewed by 3213
Abstract
Previous reports on phytochemicals in green tea (GT) and processed teas mainly focused on more representative compounds such as catechins. Here, we focus on the insignificantly studied non-catechin components in tea extracts, and explore the multivariate correlation between diverse phenolic compounds in tea [...] Read more.
Previous reports on phytochemicals in green tea (GT) and processed teas mainly focused on more representative compounds such as catechins. Here, we focus on the insignificantly studied non-catechin components in tea extracts, and explore the multivariate correlation between diverse phenolic compounds in tea and the in vitro antioxidant and anticancer effects. Extracts from GT and four types of processed teas were further divided into hydrophilic and hydrophobic fractions, whose phenolic compositions and antioxidant capacities were quantified using HPLC-MS and three antioxidant assays, respectively. For three types of teas, the anticancer effects of their extracts and fractions were assessed using cancer cell lines. The hydrophobic fractions had lower antioxidant capacities than the corresponding hydrophilic fractions, but exhibited superior antiproliferative effects on cancer cells compared with the whole extract and the hydrophilic fraction. Partial least squares-discriminant analysis revealed a strong correlation between the anticancer effects and the theaflavins and flavonols. Therefore, in addition to catechins, the hydrophobic fraction of tea extracts may have beneficial health effects. Full article
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19 pages, 2141 KiB  
Article
Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Effects of Azolla pinnata Ethanolic Extract against Lead-Induced Hepatotoxicity in Rats
by Ahmed Shaaban Abd Elrasoul, Ahmed Abdelmoniem Mousa, Sahar Hassan Orabi, Mostafa Abd El-Gaber Mohamed, Shaban M. Gad-Allah, Rafa Almeer, Mohamed M. Abdel-Daim, Shaden A. M. Khalifa, Hesham R. El-Seedi and Mabrouk Attia Abd Eldaim
Antioxidants 2020, 9(10), 1014; https://doi.org/10.3390/antiox9101014 - 19 Oct 2020
Cited by 23 | Viewed by 4310
Abstract
The current study investigated the protective potential of Azolla pinnate ethanolic extract (APE) against lead-induced hepatotoxicity in rats. Sixty male Wistar albino rats were randomly allocated into six groups (n = 10). The control group was orally administrated with saline. The second group [...] Read more.
The current study investigated the protective potential of Azolla pinnate ethanolic extract (APE) against lead-induced hepatotoxicity in rats. Sixty male Wistar albino rats were randomly allocated into six groups (n = 10). The control group was orally administrated with saline. The second group received lead acetate (100 mg/kg body weight (BW) orally for 60 days). The third group was fed with APE (10 mg/kg BW orally for 60 days). The fourth group was administrated with lead acetate like the second group and APE like the third group, concomitantly, for 60 days. The fifth group was administrated with APE like the third group for 30 days, then orally administrated with the lead acetate like the second group for another 30 days. The sixth group was administrated with lead acetate like the second group for 30 days, then with APE like the third group for a further 30 days. Phytochemical analysis of APE indicated the presence of peonidin 3-O-glucoside cation, vitexin, rutin, thiamine, choline, tamarixetin, hyperoside, astragalin, and quercetin. The latter has been elucidated using one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) and liquid chromatography–mass spectrometry (LC–MS-MS). Lead acetate increased the serum levels of alanine and aspartate aminotransferases and that of urea, creatinine, tumor necrosis factor alpha, and interleukin 1β, hepatic tissue malondialdehyde contents, and caspase 3 protein expression, as well as altering the hepatic tissue architecture. However, it decreased the serum levels of interleukin 10 and glutathione (GSH) contents, and the activities of catalase and superoxide dismutase in hepatic tissue. In contrast, the administration of APE ameliorated the lead-induced alterations in liver function and structure, exemplifying the benefits of Azolla’s phytochemical contents. Collectively, A. pinnate extract is a protective and curative agent against lead-induced hepatotoxicity via its antioxidant, anti-inflammatory, and anti-apoptotic impacts. Full article
(This article belongs to the Special Issue Antioxidants of Natural Product)
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39 pages, 579 KiB  
Review
Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue
by Gustavo Egea, Francesc Jiménez-Altayó and Victoria Campuzano
Antioxidants 2020, 9(10), 1013; https://doi.org/10.3390/antiox9101013 - 19 Oct 2020
Cited by 19 | Viewed by 4186
Abstract
Connective tissue is known to provide structural and functional “glue” properties to other tissues. It contains cellular and molecular components that are arranged in several dynamic organizations. Connective tissue is the focus of numerous genetic and nongenetic diseases. Genetic diseases of the connective [...] Read more.
Connective tissue is known to provide structural and functional “glue” properties to other tissues. It contains cellular and molecular components that are arranged in several dynamic organizations. Connective tissue is the focus of numerous genetic and nongenetic diseases. Genetic diseases of the connective tissue are minority or rare, but no less important than the nongenetic diseases. Here we review the impact of reactive oxygen species (ROS) and oxidative stress on the onset and/or progression of diseases that directly affect connective tissue and have a genetic origin. It is important to consider that ROS and oxidative stress are not synonymous, although they are often closely linked. In a normal range, ROS have a relevant physiological role, whose levels result from a fine balance between ROS producers and ROS scavenge enzymatic systems. However, pathology arises or worsens when such balance is lost, like when ROS production is abnormally and constantly high and/or when ROS scavenge (enzymatic) systems are impaired. These concepts apply to numerous diseases, and connective tissue is no exception. We have organized this review around the two basic structural molecular components of connective tissue: The ground substance and fibers (collagen and elastic fibers). Full article
(This article belongs to the Special Issue Oxidative Stress in Vascular Pathophysiology)
20 pages, 1146 KiB  
Review
Mechanisms of Chronic Metabolic Stress in Arrhythmias
by Blake H. Gowen, Michael V. Reyes, Leroy C. Joseph and John P. Morrow
Antioxidants 2020, 9(10), 1012; https://doi.org/10.3390/antiox9101012 - 19 Oct 2020
Cited by 6 | Viewed by 3489
Abstract
Cardiac arrhythmias are responsible for many cardiovascular disease-related deaths worldwide. While arrhythmia pathogenesis is complex, there is increasing evidence for metabolic causes. Obesity, diabetes, and chronically consuming high-fat foods significantly increase the likelihood of developing arrhythmias. Although these correlations are well established, mechanistic [...] Read more.
Cardiac arrhythmias are responsible for many cardiovascular disease-related deaths worldwide. While arrhythmia pathogenesis is complex, there is increasing evidence for metabolic causes. Obesity, diabetes, and chronically consuming high-fat foods significantly increase the likelihood of developing arrhythmias. Although these correlations are well established, mechanistic explanations connecting a high-fat diet (HFD) to arrhythmogenesis are incomplete, although oxidative stress appears to be critical. This review investigates the metabolic changes that occur in obesity and after HFD. Potential therapies to prevent or treat arrhythmias are discussed, including antioxidants. Full article
(This article belongs to the Special Issue Antioxidant Therapy in Cardiovascular Medicine: Bench to Bedside)
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33 pages, 2467 KiB  
Article
Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies
by Federica Fogacci, Manfredi Rizzo, Christoffer Krogager, Cormac Kennedy, Coralie M.G. Georges, Tamara Knežević, Evangelos Liberopoulos, Alexandre Vallée, Pablo Pérez-Martínez, Eliane F.E. Wenstedt, Agnė Šatrauskienė, Michal Vrablík and Arrigo F.G. Cicero
Antioxidants 2020, 9(10), 1011; https://doi.org/10.3390/antiox9101011 - 19 Oct 2020
Cited by 32 | Viewed by 7880
Abstract
Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile [...] Read more.
Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile through a systematic review of the literature and a meta-analysis of the available randomized placebo-controlled clinical studies. The literature search included EMBASE, PubMed Medline, SCOPUS, Google Scholar, and ISI Web of Science by Clarivate databases up to 15th August 2020. Data were pooled from 71 clinical studies, comprising 155 treatment arms, which included 4749 subjects with 2558 subjects treated with ALA and 2294 assigned to placebo. A meta-analysis of extracted data suggested that supplementation with ALA was not associated with an increased risk of any treatment-emergent adverse event (all p > 0.05). ALA supplementation was safe, even in subsets of studies categorized according to smoking habit, cardiovascular disease, presence of diabetes, pregnancy status, neurological disorders, rheumatic affections, severe renal impairment, and status of children/adolescents at baseline. Full article
(This article belongs to the Special Issue Role of Natural Antioxidants on Neuroprotection and Neuroinflammation)
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18 pages, 1760 KiB  
Article
Valorisation of Exhausted Olive Pomace by an Eco-Friendly Solvent Extraction Process of Natural Antioxidants
by Irene Gómez-Cruz, Cristóbal Cara, Inmaculada Romero, Eulogio Castro and Beatriz Gullón
Antioxidants 2020, 9(10), 1010; https://doi.org/10.3390/antiox9101010 - 17 Oct 2020
Cited by 32 | Viewed by 5143 | Correction
Abstract
Exhausted olive pomace (EOP) is the waste generated from the drying and subsequent extraction of residual oil from the olive pomace. In this work, the effect of different aqueous solvents on the recovery of antioxidant compounds from this lignocellulosic biomass was assessed. Water [...] Read more.
Exhausted olive pomace (EOP) is the waste generated from the drying and subsequent extraction of residual oil from the olive pomace. In this work, the effect of different aqueous solvents on the recovery of antioxidant compounds from this lignocellulosic biomass was assessed. Water extraction was selected as the best option for recovering bioactive compounds from EOP, and the influence of the main operational parameters involved in the extraction was evaluated by response surface methodology. Aqueous extraction of EOP under optimised conditions (10% solids, 85 ºC, and 90 min) yielded an extract with concentrations (per g EOP) of phenolic compounds and flavonoids of 44.5 mg gallic acid equivalent and 114.9 mg rutin equivalent, respectively. Hydroxytyrosol was identified as the major phenolic compound in EOP aqueous extracts. Moreover, these extracts showed high antioxidant activity, as well as moderate bactericidal action against some food-borne pathogens. In general, these results indicate the great potential of EOP as a source of bioactive compounds, with potential uses in several industrial applications. Full article
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13 pages, 640 KiB  
Article
Conservation of Native Wild Ivory-White Olives from the MEDES Islands Natural Reserve to Maintain Virgin Olive Oil Diversity
by Anallely López-Yerena, Antònia Ninot, Julián Lozano-Castellón, Elvira Escribano-Ferrer, Agustí J. Romero-Aroca, Angjelina Belaj, Anna Vallverdú-Queralt and Rosa M. Lamuela-Raventós
Antioxidants 2020, 9(10), 1009; https://doi.org/10.3390/antiox9101009 - 17 Oct 2020
Cited by 12 | Viewed by 6168
Abstract
Food diversity, and in particular genetic diversity, is being lost at an alarming rate. Protection of natural areas is crucial to safeguard the world’s threatened species. The Medes Islands (MI), located in the northwest Mediterranean Sea, are a protected natural reserve. Wild olive [...] Read more.
Food diversity, and in particular genetic diversity, is being lost at an alarming rate. Protection of natural areas is crucial to safeguard the world’s threatened species. The Medes Islands (MI), located in the northwest Mediterranean Sea, are a protected natural reserve. Wild olive trees also known as oleasters make up part of the vegetation of the Meda Gran island. Among them, in 2012, a wild albino ivory-white olive tree with fruit was identified. Fruits were collected from this tree and their seeds were first sown in a greenhouse and then planted in an orchard for purposes of ex situ preservation. Seven out of the 78 seedling trees obtained (12%) produced ivory-white fruits. In autumn 2018, fruits from these trees were sampled. Although the fruits had low oil content, virgin olive oil with unique sensory, physicochemical, and stability characteristics was produced. With respect to the polyphenols content, oleacein was the main compound identified (373.29 ± 72.02 mg/kg) and the oleocanthal was the second most abundant phenolic compound (204.84 ± 52.58 mg/kg). Regarding pigments, samples were characterized by an intense yellow color, with 12.5 ± 4.6 mg/kg of chlorophyll and 9.2 ± 3.3 mg/kg of carotenoids. Finally, oleic acid was the main fatty acid identified. This study explored the resources of the natural habitat of the MI as a means of enrichment of olive oil diversity and authenticity of this traditional Mediterranean food Full article
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17 pages, 1621 KiB  
Article
The Protective Role of Bioactive Quinones in Stress-induced Senescence Phenotype of Endothelial Cells Exposed to Cigarette Smoke Extract
by Ilenia Cirilli, Patrick Orlando, Fabio Marcheggiani, Phiwayinkosi V. Dludla, Sonia Silvestri, Elisabetta Damiani and Luca Tiano
Antioxidants 2020, 9(10), 1008; https://doi.org/10.3390/antiox9101008 - 16 Oct 2020
Cited by 18 | Viewed by 3206
Abstract
Endothelial dysfunction represents the initial stage in atherosclerotic lesion development which occurs physiologically during aging, but external factors like diet, sedentary lifestyle, smoking accelerate it. Since cigarette smoking promotes oxidative stress and cell damage, we developed an in vitro model of endothelial dysfunction [...] Read more.
Endothelial dysfunction represents the initial stage in atherosclerotic lesion development which occurs physiologically during aging, but external factors like diet, sedentary lifestyle, smoking accelerate it. Since cigarette smoking promotes oxidative stress and cell damage, we developed an in vitro model of endothelial dysfunction using vascular cells exposed to chemicals present in cigarette smoke, to help elucidate the protective effects of anti-inflammatory and antioxidant agents, such as ubiquinol and vitamin K, that play a fundamental role in vascular health. Treatment of both young and senescent Human Umbilical Vein Endothelial Cells (HUVECs) for 24 h with cigarette smoke extract (CSE) decreased cellular viability, induced apoptosis via reactive oxygen species (ROS) imbalance and mitochondrial dysfunction and promoted an inflammatory response. Moreover, the senescence marker SA-β-galactosidase was observed in both young CSE-exposed and in senescent HUVECs suggesting that CSE exposure accelerates aging in endothelial cells. Supplementation with 10 µM ubiquinol and menaquinone-7 (MK7) counteracted oxidative stress and inflammation, resulting in improved viability, decreased apoptosis and reduced SA-β-galactosidase, but were ineffective against CSE-induced mitochondrial permeability transition pore opening. Other K vitamins tested like menaquinone-4 (MK4) and menaquinone-1 (K1) were less protective. In conclusion, CSE exposure was able to promote a stress-induced senescent phenotype in young endothelial cells likely contributing to endothelial dysfunction in vivo. Furthermore, the molecular changes encountered could be offset by ubiquinol and menaquinone-7 supplementation, the latter resulting the most bioactive K vitamin in counteracting CSE-induced damage. Full article
(This article belongs to the Special Issue Feature Papers in Antioxidants in 2020)
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51 pages, 3211 KiB  
Review
Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease
by E. Maruthi Prasad and Shih-Ya Hung
Antioxidants 2020, 9(10), 1007; https://doi.org/10.3390/antiox9101007 - 16 Oct 2020
Cited by 48 | Viewed by 8003
Abstract
Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes [...] Read more.
Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP+), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms’ treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms. Full article
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15 pages, 1285 KiB  
Article
Protection of Polyphenols against Glyco-Oxidative Stress: Involvement of Glyoxalase Pathway
by Laura Cianfruglia, Camilla Morresi, Tiziana Bacchetti, Tatiana Armeni and Gianna Ferretti
Antioxidants 2020, 9(10), 1006; https://doi.org/10.3390/antiox9101006 - 16 Oct 2020
Cited by 13 | Viewed by 3980
Abstract
Chronic high glucose (HG) exposure increases methylglyoxal (MGO)-derived advanced glycation end-products (AGEs) and is involved in the onset of pathological conditions, such as diabetes, atherosclerosis and chronic-degenerative diseases. Under physiologic conditions the harmful effects of MGO are contrasted by glyoxalase system that is [...] Read more.
Chronic high glucose (HG) exposure increases methylglyoxal (MGO)-derived advanced glycation end-products (AGEs) and is involved in the onset of pathological conditions, such as diabetes, atherosclerosis and chronic-degenerative diseases. Under physiologic conditions the harmful effects of MGO are contrasted by glyoxalase system that is implicated in the detoxification of Reactive Carbonyl Species (RCS) and maintain the homeostasis of the redox environment of the cell. Polyphenols are the most abundant antioxidants in the diet and present various health benefits. Aims of the study were to investigate the effects of HG-chronic exposure on glyco-oxidation and glyoxalase system in intestinal cells, using CaCo-2 cells. Moreover, we studied the effect of apple polyphenols on glyco-oxidative stress. Our data demonstrated that HG-treatment triggers glyco-oxidation stress with a significant increase in intracellular Reactive Oxygen Species (ROS), lipid peroxidation, AGEs, and increase of Glyoxalase I (GlxI) activity. On the contrary, Glyoxalase II (GlxII) activity was lower in HG-treated cells. We demonstrate that apple polyphenols exert a protective effect against oxidative stress and dicarbonyl stress. The increase of total antioxidant capacity and glutathione (GSH) levels in HG-treated cells in the presence of apple polyphenols was associated with a decrease of GlxI activity. Full article
(This article belongs to the Special Issue Redox Biology of Glyoxalases)
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17 pages, 22400 KiB  
Article
Antioxidant Carbon Nanoparticles Inhibit Fibroblast-Like Synoviocyte Invasiveness and Reduce Disease Severity in a Rat Model of Rheumatoid Arthritis
by Mark R. Tanner, Redwan Huq, William K. A. Sikkema, Lizanne G. Nilewski, Nejla Yosef, Cody Schmitt, Carlos P. Flores-Suarez, Arielle Raugh, Teresina Laragione, Pércio S. Gulko, James M. Tour and Christine Beeton
Antioxidants 2020, 9(10), 1005; https://doi.org/10.3390/antiox9101005 - 16 Oct 2020
Cited by 3 | Viewed by 2625
Abstract
Reactive oxygen species have been involved in the pathogenesis of rheumatoid arthritis (RA). Our goal was to determine the effects of selectively scavenging superoxide (O2•−) and hydroxyl radicals with antioxidant nanoparticles, called poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), on the [...] Read more.
Reactive oxygen species have been involved in the pathogenesis of rheumatoid arthritis (RA). Our goal was to determine the effects of selectively scavenging superoxide (O2•−) and hydroxyl radicals with antioxidant nanoparticles, called poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), on the pathogenic functions of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and on the progression of an animal model of RA. We used human FLS from patients with RA to determine PEG-HCC internalization and effects on FLS cytotoxicity, invasiveness, proliferation, and production of proteases. We used the pristane-induced arthritis (PIA) rat model of RA to assess the benefits of PEG-HCCs on reducing disease severity. PEG-HCCs were internalized by RA-FLS, reduced their intracellular O2•−, and reduced multiple measures of their pathogenicity in vitro, including proliferation and invasion. In PIA, PEG-HCCs caused a 65% reduction in disease severity, as measured by a standardized scoring system of paw inflammation and caused a significant reduction in bone and tissue damage, and circulating rheumatoid factor. PEG-HCCs did not induce lymphopenia during PIA. Our study demonstrated a role for O2•− and hydroxyl radicals in the pathogenesis of a rat model of RA and showed efficacy of PEG-HCCs in treating a rat model of RA. Full article
(This article belongs to the Special Issue Nanoantioxidants)
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20 pages, 5876 KiB  
Review
Methylmercury-Mediated Oxidative Stress and Activation of the Cellular Protective System
by Masatake Fujimura and Fusako Usuki
Antioxidants 2020, 9(10), 1004; https://doi.org/10.3390/antiox9101004 - 16 Oct 2020
Cited by 22 | Viewed by 3049
Abstract
Methylmercury (MeHg) is a well-known neurotoxicant that causes severe intoxication in humans. In Japan, it is referred to as Minamata disease, which involves two characteristic clinical forms: fetal type and adult type depending on the exposed age. In addition to MeHg burden level, [...] Read more.
Methylmercury (MeHg) is a well-known neurotoxicant that causes severe intoxication in humans. In Japan, it is referred to as Minamata disease, which involves two characteristic clinical forms: fetal type and adult type depending on the exposed age. In addition to MeHg burden level, individual susceptibility to MeHg plays a role in the manifestation of MeHg toxicity. Research progress has pointed out the importance of oxidative stress in the pathogenesis of MeHg toxicity. MeHg has a high affinity for selenohydryl groups, sulfhydryl groups, and selenides. It has been clarified that such affinity characteristics cause the impairment of antioxidant enzymes and proteins, resulting in the disruption of antioxidant systems. Furthermore, MeHg-induced intracellular selenium deficiency due to the greater affinity of MeHg for selenohydryl groups and selenides leads to failure in the recoding of a UGA codon for selenocysteine and results in the degradation of antioxidant selenoenzyme mRNA by nonsense-mediated mRNA decay. The defect of antioxidant selenoenzyme replenishment exacerbates MeHg-mediated oxidative stress. On the other hand, it has also been revealed that MeHg can directly activate the antioxidant Keap1/Nrf2 signaling pathway. This review summarizes the incidence of MeHg-mediated oxidative stress from the viewpoint of the individual intracellular redox system interactions and the MeHg-mediated aforementioned intracellular events. In addition, the mechanisms of cellular stress pathways and neuronal cell death triggered by MeHg-mediated oxidative stress and direct interactions of MeHg with reactive residues of proteins are mentioned. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Toxicology)
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22 pages, 3392 KiB  
Article
Allium subhirsutum L. as a Potential Source of Antioxidant and Anticancer Bioactive Molecules: HR-LCMS Phytochemical Profiling, In Vitro and In Vivo Pharmacological Study
by Riadh Badraoui, Tarek Rebai, Salem Elkahoui, Mousa Alreshidi, Vajid N. Veettil, Emira Noumi, Khaled A. Al-Motair, Kaïss Aouadi, Adel Kadri, Vincenzo De Feo and Mejdi Snoussi
Antioxidants 2020, 9(10), 1003; https://doi.org/10.3390/antiox9101003 - 16 Oct 2020
Cited by 34 | Viewed by 3229
Abstract
This study investigated Allium subhirsutum L. (AS) anticancer and antioxidant effects and inhibition of tumor angiogenesis in a murine model of skeletal metastases due to inoculation of Walker 256/B cells. Phytochemical composition of AS extract (ASE) was studied by High Resolution-Liquid Chromatography Mass [...] Read more.
This study investigated Allium subhirsutum L. (AS) anticancer and antioxidant effects and inhibition of tumor angiogenesis in a murine model of skeletal metastases due to inoculation of Walker 256/B cells. Phytochemical composition of AS extract (ASE) was studied by High Resolution-Liquid Chromatography Mass Spectroscopy (HR-LCMS). Total phenolic and flavonoid contents (TPC and TFC) were determined. In vitro, the antioxidant properties were evaluated by reducing power and antiradical activity against DPPH. Cancer cells’ proliferation, apoptosis, metastatic development and angiogenesis were evaluated using Walker 256/B and MatLyLu cells. The p-coumaric acid was the major phenolic acid (1700 µg/g extract). ASE showed high levels of TPC and TFC and proved potent antioxidant effects. ASE inhibited Walker 256/B and MatLyLu cells’ proliferation (Half-maximal inhibitory concentration: IC50 ≃ 150 µg/mL) and induced apoptosis. In silico and in vivo assays confirmed these findings. ASE effectively acts as a chemo-preventive compound, induces apoptosis and attenuates angiogenesis and osteolytic metastases due to Walker 256/B malignant cells. Full article
(This article belongs to the Special Issue Antioxidant and Biological Properties of Plant Extracts)
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26 pages, 3944 KiB  
Review
An Overview of the Genus Cotoneaster (Rosaceae): Phytochemistry, Biological Activity, and Toxicology
by Agnieszka Kicel
Antioxidants 2020, 9(10), 1002; https://doi.org/10.3390/antiox9101002 - 16 Oct 2020
Cited by 9 | Viewed by 6551
Abstract
Traditional herbal medicines have become a subject of global importance with both medical and economic implications. The regular consumption of herbal drugs has led to serious concerns regarding their quality, effectiveness, and safety. Thus, relevant scientific evidence has become an important criterion for [...] Read more.
Traditional herbal medicines have become a subject of global importance with both medical and economic implications. The regular consumption of herbal drugs has led to serious concerns regarding their quality, effectiveness, and safety. Thus, relevant scientific evidence has become an important criterion for the acceptance of traditional health claims. The genus Cotoneaster Medikus provides numerous species traditionally used in Asian medicine for the treatment of haemorrhoids, diabetes, and cardiovascular diseases. This review summarises the achievements of modern research on the Cotoneaster taxa, including ethnobotany, phytochemistry, pharmacology, and toxicology. To date, more than 90 compounds have been isolated or analytically identified in Cotoneaster leaves, fruits, flowers or twigs. These phytochemicals are categorised into flavonoids, procyanidins, phenolic acids, cotonefurans, cyanogenic glycosides, triterpenes, sterols, fatty acids, volatile compounds, and carbohydrates, and many of them are responsible for Cotoneaster pharmacological properties including antioxidant, anti-inflammatory, antimicrobial, antiparasitic, hepatoprotective, anti-diabetic or anti-dyslipidaemic activity. In order to ensure the safety of pharmaceutical applications, the potential toxicity of Cotoneaster extracts has also been investigated. In conclusion, this systematic review provides an important reference base for further study into the various medical applications of both the dry extracts and pure isolates of Cotoneaster species. Full article
(This article belongs to the Special Issue Phenolics as Antioxidant Agents)
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36 pages, 2118 KiB  
Review
Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling
by Simin Yan, Thomas C. Resta and Nikki L. Jernigan
Antioxidants 2020, 9(10), 999; https://doi.org/10.3390/antiox9100999 - 15 Oct 2020
Cited by 22 | Viewed by 5939
Abstract
Elevated resistance of pulmonary circulation after chronic hypoxia exposure leads to pulmonary hypertension. Contributing to this pathological process is enhanced pulmonary vasoconstriction through both calcium-dependent and calcium sensitization mechanisms. Reactive oxygen species (ROS), as a result of increased enzymatic production and/or decreased scavenging, [...] Read more.
Elevated resistance of pulmonary circulation after chronic hypoxia exposure leads to pulmonary hypertension. Contributing to this pathological process is enhanced pulmonary vasoconstriction through both calcium-dependent and calcium sensitization mechanisms. Reactive oxygen species (ROS), as a result of increased enzymatic production and/or decreased scavenging, participate in augmentation of pulmonary arterial constriction by potentiating calcium influx as well as activation of myofilament sensitization, therefore mediating the development of pulmonary hypertension. Here, we review the effects of chronic hypoxia on sources of ROS within the pulmonary vasculature including NADPH oxidases, mitochondria, uncoupled endothelial nitric oxide synthase, xanthine oxidase, monoamine oxidases and dysfunctional superoxide dismutases. We also summarize the ROS-induced functional alterations of various Ca2+ and K+ channels involved in regulating Ca2+ influx, and of Rho kinase that is responsible for myofilament Ca2+ sensitivity. A variety of antioxidants have been shown to have beneficial therapeutic effects in animal models of pulmonary hypertension, supporting the role of ROS in the development of pulmonary hypertension. A better understanding of the mechanisms by which ROS enhance vasoconstriction will be useful in evaluating the efficacy of antioxidants for the treatment of pulmonary hypertension. Full article
(This article belongs to the Special Issue Oxidative Stress in Vascular Pathophysiology)
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24 pages, 2140 KiB  
Review
Solid Lipid Nanoparticles as Carriers of Natural Phenolic Compounds
by Alexandra Borges, Victor de Freitas, Nuno Mateus, Iva Fernandes and Joana Oliveira
Antioxidants 2020, 9(10), 998; https://doi.org/10.3390/antiox9100998 - 15 Oct 2020
Cited by 86 | Viewed by 8813
Abstract
Phenolic compounds are one of the most widespread classes of compounds in nature, with several beneficial biological effects being associated with their anti-oxidant and anti-carcinogenic activities. Their application in the prevention or treatment of numerous chronic diseases have been studied, but a major [...] Read more.
Phenolic compounds are one of the most widespread classes of compounds in nature, with several beneficial biological effects being associated with their anti-oxidant and anti-carcinogenic activities. Their application in the prevention or treatment of numerous chronic diseases have been studied, but a major drawback is still the low bioavailability of these compounds, as well as their instability towards pH, temperature, and light in some cases. Nanotechnology has emerged as an alternative to overcome these limitations, and the use of lipidic encapsulation systems is a promising technique to achieve an efficient drug delivery, protecting molecules from external factors and improving their bioavailability. In this review, solid lipid nanoparticles and nanostructured lipid carriers are highlighted as an important tool for the improvement of the bioavailability and stability of natural phenolic compounds, including their preparation methods and functionalization approaches and the discussion of several applications for putative use in cosmetic and pharmacologic products. Full article
(This article belongs to the Special Issue Lipid Nanostructures for Antioxidant Delivery)
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16 pages, 3561 KiB  
Article
Vitamin D Deficiency Induces Elevated Oxidative and Biomechanical Damage in Coronary Arterioles in Male Rats
by Réka Eszter Sziva, Zoltán Fontányi, Éva Pál, Leila Hadjadj, Anna Monori-Kiss, Eszter Mária Horváth, Rita Benkő, Attila Magyar, Andrea Heinzlmann, Zoltán Benyó, György L. Nádasy and Szabolcs Várbíró
Antioxidants 2020, 9(10), 997; https://doi.org/10.3390/antiox9100997 - 15 Oct 2020
Cited by 8 | Viewed by 5061
Abstract
Background: Several reports prove interconnection between vitamin D (VD) deficiency and increased cardiovascular risk. Our aim was to investigate the effects of VD status on biomechanical and oxidative–nitrative (O–N) stress parameters of coronary arterioles in rats. Methods: 4-week-old male Wistar rats were divided [...] Read more.
Background: Several reports prove interconnection between vitamin D (VD) deficiency and increased cardiovascular risk. Our aim was to investigate the effects of VD status on biomechanical and oxidative–nitrative (O–N) stress parameters of coronary arterioles in rats. Methods: 4-week-old male Wistar rats were divided into a control group (11 animals) with optimal VD supply (300 IU/kgbw/day) and a VD-deficient group (11 animals, <5 IU/kg/day). After 8 weeks, coronary arteriole segments were prepared. Geometrical, elastic, and biomechanical characteristics were measured by in vitro arteriography. O–N stress markers were investigated by immunohistochemistry. Results: Inner radius decreased; wall thickness and wall-thickness/lumen diameter ratio increased; tangential wall stress and elastic modulus were reduced in VD-deficient group. No difference could be found in wall-cross-sectional area, intima-media area %. While the elastic elements of the vessel wall decreased, the α-smooth muscle actin (α-SMA) immunostaining intensity showed no changes. Significant elevation was found in the lipid peroxidation marker of 4-hidroxy-2-nonenal (HNE), while other O–N stress markers staining intensity (poly(ADP)ribose, 3-nitrotyrosine) did not change. Conclusions: Inward eutrophic remodeling has developed. The potential background of these impairments may involve the initial change in oxidative damage markers (HNE). These mechanisms can contribute to the increased incidence of the cardiovascular diseases in VD deficiency. Full article
(This article belongs to the Special Issue Oxidative-Nitrative Stress in Human Health and Disease)
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