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Antioxidants
Volume 12
Issue 4
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Antioxidants, Volume 12, Issue 4 (April 2023) – 200 articles

Cover Story (view full-size image): Complex molecular interactions drive biological processes in response to environmental exposures. Understanding antagonistic interactions is important because pathologic outcomes can result from adverse responses or failure of beneficial mechanisms. Environmental metal manganese is beneficial at low doses but a neurotoxicant at high doses and is suitable for the study of antagonistic interactions. Utilizing an advanced multi-omics approach, we show that metabolite and transcript changes can be combined with cellular and mitochondrial specific responses to provide a systems view of underlying neurotoxic mechanisms. Our results show that antagonistic interactions reflect mechanisms of mitochondrial oxidative stress, cellular thiol oxidation and protective effects of mitochondrial bioenergetics. View this paper
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25 pages, 5706 KiB  
Article
Protective Effect of Dexmedetomidine against Hyperoxia-Damaged Cerebellar Neurodevelopment in the Juvenile Rat
by Robert Puls, Clarissa von Haefen, Christoph Bührer and Stefanie Endesfelder
Antioxidants 2023, 12(4), 980; https://doi.org/10.3390/antiox12040980 - 21 Apr 2023
Cited by 2 | Viewed by 1736
Abstract
Impaired cerebellar development of premature infants and the associated impairment of cerebellar functions in cognitive development could be crucial factors for neurodevelopmental disorders. Anesthetic- and hyperoxia-induced neurotoxicity of the immature brain can lead to learning and behavioral disorders. Dexmedetomidine (DEX), which is associated [...] Read more.
Impaired cerebellar development of premature infants and the associated impairment of cerebellar functions in cognitive development could be crucial factors for neurodevelopmental disorders. Anesthetic- and hyperoxia-induced neurotoxicity of the immature brain can lead to learning and behavioral disorders. Dexmedetomidine (DEX), which is associated with neuroprotective properties, is increasingly being studied for off-label use in the NICU. For this purpose, six-day-old Wistar rats (P6) were exposed to hyperoxia (80% O2) or normoxia (21% O2) for 24 h after DEX (5 µg/kg, i.p.) or vehicle (0.9% NaCl) application. An initial detection in the immature rat cerebellum was performed after the termination of hyperoxia at P7 and then after recovery in room air at P9, P11, and P14. Hyperoxia reduced the proportion of Calb1+-Purkinje cells and affected the dendrite length at P7 and/or P9/P11. Proliferating Pax6+-granule progenitors remained reduced after hyperoxia and until P14. The expression of neurotrophins and neuronal transcription factors/markers of proliferation, migration, and survival were also reduced by oxidative stress in different manners. DEX demonstrated protective effects on hyperoxia-injured Purkinje cells, and DEX without hyperoxia modulated neuronal transcription in the short term without any effects at the cellular level. DEX protects hyperoxia-damaged Purkinje cells and appears to differentially affect cerebellar granular cell neurogenesis following oxidative stress. Full article
(This article belongs to the Special Issue The Role of Antioxidants in Pregnant Woman and Child’s Health)
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24 pages, 4629 KiB  
Review
Grape Pomace as a Cardiometabolic Health-Promoting Ingredient: Activity in the Intestinal Environment
by Diego Taladrid, Miguel Rebollo-Hernanz, Maria A. Martin-Cabrejas, M. Victoria Moreno-Arribas and Begoña Bartolomé
Antioxidants 2023, 12(4), 979; https://doi.org/10.3390/antiox12040979 - 21 Apr 2023
Cited by 7 | Viewed by 2939
Abstract
Grape pomace (GP) is a winemaking by-product particularly rich in (poly)phenols and dietary fiber, which are the main active compounds responsible for its health-promoting effects. These components and their metabolites generated at the intestinal level have been shown to play an important role [...] Read more.
Grape pomace (GP) is a winemaking by-product particularly rich in (poly)phenols and dietary fiber, which are the main active compounds responsible for its health-promoting effects. These components and their metabolites generated at the intestinal level have been shown to play an important role in promoting health locally and systemically. This review focuses on the potential bioactivities of GP in the intestinal environment, which is the primary site of interaction for food components and their biological activities. These mechanisms include (i) regulation of nutrient digestion and absorption (GP has been shown to inhibit enzymes such as α-amylase and α-glucosidase, protease, and lipase, which can help to reduce blood glucose and lipid levels, and to modulate the expression of intestinal transporters, which can also help to regulate nutrient absorption); (ii) modulation of gut hormone levels and satiety (GP stimulates GLP-1, PYY, CCK, ghrelin, and GIP release, which can help to regulate appetite and satiety); (iii) reinforcement of gut morphology (including the crypt-villi structures, which can improve nutrient absorption and protect against intestinal damage); (iv) protection of intestinal barrier integrity (through tight junctions and paracellular transport); (v) modulation of inflammation and oxidative stress triggered by NF-kB and Nrf2 signaling pathways; and (vi) impact on gut microbiota composition and functionality (leading to increased production of SCFAs and decreased production of LPS). The overall effect of GP within the gut environment reinforces the intestinal function as the first line of defense against multiple disorders, including those impacting cardiometabolic health. Future research on GP’s health-promoting properties should consider connections between the gut and other organs, including the gut-heart axis, gut-brain axis, gut-skin axis, and oral-gut axis. Further exploration of these connections, including more human studies, will solidify GP’s role as a cardiometabolic health-promoting ingredient and contribute to the prevention and management of cardiovascular diseases. Full article
(This article belongs to the Special Issue Antioxidant Foods and Cardiometabolic Health - 2nd Edition)
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19 pages, 4791 KiB  
Article
The Prebiotic Effects of an Extract with Antioxidant Properties from Morus alba L. Contribute to Ameliorate High-Fat Diet-Induced Obesity in Mice
by María Jesús Rodríguez-Sojo, Antonio Jesús Ruiz-Malagón, Laura Hidalgo-García, Jose Alberto Molina-Tijeras, Patricia Diez-Echave, Laura López-Escanez, Lucrezia Rosati, Elena González-Lozano, Laura Cenis-Cifuentes, Jorge García-García, Federico García, Iñaki Robles-Vera, Miguel Romero, Juan Duarte, José Luis Cenis, Antonio Abel Lozano-Pérez, Julio Gálvez, María Elena Rodríguez-Cabezas and Alba Rodríguez-Nogales
Antioxidants 2023, 12(4), 978; https://doi.org/10.3390/antiox12040978 - 21 Apr 2023
Cited by 1 | Viewed by 2630
Abstract
Obesity is a global health issue, in which modifications in gut microbiota composition have a key role. Different therapeutic strategies are being developed in combination with diet and exercise, including the use of plant extracts, such as those obtained from Morus alba L. [...] Read more.
Obesity is a global health issue, in which modifications in gut microbiota composition have a key role. Different therapeutic strategies are being developed in combination with diet and exercise, including the use of plant extracts, such as those obtained from Morus alba L. leaves. Recent studies have revealed their anti-inflammatory and antioxidant properties. The aim of the present work was to evaluate whether the beneficial effects of M. alba L. leaf extract in high-fat diet-induced obesity in mice is correlated with its impact on gut microbiota. The extract reduced body weight gain and attenuated lipid accumulation, as well as increased glucose sensitivity. These effects were associated with an amelioration of the obesity-associated inflammatory status, most probably due to the described antioxidant properties of the extract. Moreover, M. alba L. leaf extract mitigated gut dysbiosis, which was evidenced by the restoration of the Firmicutes/Bacteroidota ratio and the decrease in plasma lipopolysaccharide (LPS) levels. Specifically, the extract administration reduced Alistipes and increased Faecalibaculum abundance, these effects being correlated with the beneficial effects exerted by the extract on the obesity-associated inflammation. In conclusion, anti-obesogenic effects of M. alba L. leaf extract may be mediated through the amelioration of gut dysbiosis. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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33 pages, 9581 KiB  
Article
New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors
by Neda Anastassova, Denitsa Stefanova, Nadya Hristova-Avakumova, Irina Georgieva, Magdalena Kondeva-Burdina, Miroslav Rangelov, Nadezhda Todorova, Rumiana Tzoneva and Denitsa Yancheva
Antioxidants 2023, 12(4), 977; https://doi.org/10.3390/antiox12040977 - 21 Apr 2023
Cited by 2 | Viewed by 1633
Abstract
In light of the known neuroprotective properties of indole compounds and the promising potential of hydrazone derivatives, two series of aldehyde-heterocyclic hybrids combining those pharmacophores were synthesized as new multifunctional neuroprotectors. The obtained derivatives of indole-3-propionic acid (IPA) and 5-methoxy-indole carboxylic acid (5MICA) [...] Read more.
In light of the known neuroprotective properties of indole compounds and the promising potential of hydrazone derivatives, two series of aldehyde-heterocyclic hybrids combining those pharmacophores were synthesized as new multifunctional neuroprotectors. The obtained derivatives of indole-3-propionic acid (IPA) and 5-methoxy-indole carboxylic acid (5MICA) had good safety profiles: Hemolytic effects < 5% (200 μM) and IC50 > 150 µM were found in the majority of the SH-SY5Y and bEnd3 cell lines. The 2,3-dihydroxy, 2-hydroxy-4-methoxy, and syringaldehyde derivatives of 5MICA exhibited the strongest neuroprotection against H2O2-induced oxidative stress in SH-SY5Y cells and 6-OHDA-induced neurotoxicity in rat-brain synaptosomes. All the compounds suppressed the iron-induced lipid peroxidation. The hydroxyl derivatives were also the most active in terms of deoxyribose-degradation inhibition, whereas the 3,4-dihydroxy derivatives were able to decrease the superoxide-anion generation. Both series of compounds showed an increased inhibition of hMAO-B, with greater expression detected in the 5MICA hybrids. The in vitro BBB model with the bEnd3 cell line showed that some compounds increased the permeability of the endothelial monolayer while maintaining the tight junctions. The combined results demonstrated that the derivatives of IPA and 5MICA showed strong neuroprotective, antioxidant, MAO-B inhibitory activity and could be considered as prospective multifunctional compounds for the treatment of neurodegenerative disorders. Full article
(This article belongs to the Special Issue 10th Anniversary of Antioxidants-Advances in Health Outcomes of Oxidative Stress)
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22 pages, 1407 KiB  
Review
Interaction between Dietary Fibre and Bioactive Compounds in Plant By-Products: Impact on Bioaccessibility and Bioavailability
by Vanesa Núñez-Gómez, Rocío González-Barrio and María Jesús Periago
Antioxidants 2023, 12(4), 976; https://doi.org/10.3390/antiox12040976 - 21 Apr 2023
Cited by 8 | Viewed by 2655
Abstract
In Europe, around 31 million tonnes of food by-products are generated during primary production and trade. The management of these by-products may cause a negative impact, both at the economic and environmental levels, for both industry and society. In this regard, taking into [...] Read more.
In Europe, around 31 million tonnes of food by-products are generated during primary production and trade. The management of these by-products may cause a negative impact, both at the economic and environmental levels, for both industry and society. In this regard, taking into consideration that these by-products retain the dietary fibre compositions and the bioactive compounds of the starting materials, plant food agro-industries have an interest in taking advantage of them, from a nutritional point of view. Therefore, this review evaluates the role of dietary fibre and bioactive compounds in these by-products as well as the potential interactions of both components and their implications for health, since the bioactive compounds associated with fibre may reach the colon, where they can be metabolised into postbiotic compounds, providing important health benefits (prebiotic, antioxidant, anti-inflammatory, etc.). Consequently, this aspect, on which there are few studies, is very relevant and must be considered in the revaluation of by-products to obtain new ingredients for food processing with improved nutritional and technological properties. Full article
(This article belongs to the Special Issue Antioxidants in Food, Food Waste, and By-Product)
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45 pages, 1737 KiB  
Systematic Review
Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment
by Giuseppe De Simone, Benedetta Mazza, Licia Vellucci, Annarita Barone, Mariateresa Ciccarelli and Andrea de Bartolomeis
Antioxidants 2023, 12(4), 975; https://doi.org/10.3390/antiox12040975 - 21 Apr 2023
Cited by 5 | Viewed by 3109
Abstract
Schizophrenia is a worldwide mental illness characterized by alterations at dopaminergic and glutamatergic synapses resulting in global dysconnectivity within and between brain networks. Impairments in inflammatory processes, mitochondrial functions, energy expenditure, and oxidative stress have been extensively associated with schizophrenia pathophysiology. Antipsychotics, the [...] Read more.
Schizophrenia is a worldwide mental illness characterized by alterations at dopaminergic and glutamatergic synapses resulting in global dysconnectivity within and between brain networks. Impairments in inflammatory processes, mitochondrial functions, energy expenditure, and oxidative stress have been extensively associated with schizophrenia pathophysiology. Antipsychotics, the mainstay of schizophrenia pharmacological treatment and all sharing the common feature of dopamine D2 receptor occupancy, may affect antioxidant pathways as well as mitochondrial protein levels and gene expression. Here, we systematically reviewed the available evidence on antioxidants’ mechanisms in antipsychotic action and the impact of first- and second-generation compounds on mitochondrial functions and oxidative stress. We further focused on clinical trials addressing the efficacy and tolerability of antioxidants as an augmentation strategy of antipsychotic treatment. EMBASE, Scopus, and Medline/PubMed databases were interrogated. The selection process was conducted in respect of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Several mitochondrial proteins involved in cell viability, energy metabolism, and regulation of oxidative systems were reported to be significantly modified by antipsychotic treatment with differences between first- and second-generation drugs. Finally, antioxidants may affect cognitive and psychotic symptoms in patients with schizophrenia, and although the evidence is only preliminary, the results indicate that further studies are warranted. Full article
(This article belongs to the Special Issue The Versatility of Mitochondrial Calcium: Insights in the Regulation of Redox Signaling)
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17 pages, 4172 KiB  
Article
Hepatitis Delta Virus Antigens Trigger Oxidative Stress, Activate Antioxidant Nrf2/ARE Pathway, and Induce Unfolded Protein Response
by Olga A. Smirnova, Olga N. Ivanova, Furkat Mukhtarov, Vladimir T. Valuev-Elliston, Artemy P. Fedulov, Petr M. Rubtsov, Natalia F. Zakirova, Sergey N. Kochetkov, Birke Bartosch and Alexander V. Ivanov
Antioxidants 2023, 12(4), 974; https://doi.org/10.3390/antiox12040974 - 21 Apr 2023
Cited by 2 | Viewed by 1929
Abstract
Hepatitis delta virus (HDV) is a viroid-like satellite that may co-infect individuals together with hepatitis B virus (HBV), as well as cause superinfection by infecting patients with chronic hepatitis B (CHB). Being a defective virus, HDV requires HBV structural proteins for virion production. [...] Read more.
Hepatitis delta virus (HDV) is a viroid-like satellite that may co-infect individuals together with hepatitis B virus (HBV), as well as cause superinfection by infecting patients with chronic hepatitis B (CHB). Being a defective virus, HDV requires HBV structural proteins for virion production. Although the virus encodes just two forms of its single antigen, it enhances the progression of liver disease to cirrhosis in CHB patients and increases the incidence of hepatocellular carcinoma. HDV pathogenesis so far has been attributed to virus-induced humoral and cellular immune responses, while other factors have been neglected. Here, we evaluated the impact of the virus on the redox status of hepatocytes, as oxidative stress is believed to contribute to the pathogenesis of various viruses, including HBV and hepatitis C virus (HCV). We show that the overexpression of large HDV antigen (L-HDAg) or autonomous replication of the viral genome in cells leads to increased production of reactive oxygen species (ROS). It also leads to the upregulated expression of NADPH oxidases 1 and 4, cytochrome P450 2E1, and ER oxidoreductin 1α, which have previously been shown to mediate oxidative stress induced by HCV. Both HDV antigens also activated the Nrf2/ARE pathway, which controls the expression of a spectrum of antioxidant enzymes. Finally, HDV and its large antigen also induced endoplasmic reticulum (ER) stress and the concomitant unfolded protein response (UPR). In conclusion, HDV may enhance oxidative and ER stress induced by HBV, thus aggravating HBV-associated pathologies, including inflammation, liver fibrosis, and the development of cirrhosis and hepatocellular carcinoma. Full article
(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)
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16 pages, 737 KiB  
Review
Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease
by Lauren H. Fairley, Shatarupa Das, Vivek Dharwal, Nadia Amorim, Karl J. Hegarty, Ridhima Wadhwa, Guntipally Mounika and Philip M. Hansbro
Antioxidants 2023, 12(4), 973; https://doi.org/10.3390/antiox12040973 - 21 Apr 2023
Cited by 5 | Viewed by 2427
Abstract
Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging and cellular senescence. Evidence suggests that oxidative damage is not solely due to exogenous exposure to inhaled irritants, but also endogenous sources of [...] Read more.
Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging and cellular senescence. Evidence suggests that oxidative damage is not solely due to exogenous exposure to inhaled irritants, but also endogenous sources of oxidants in the form of reactive oxygen species (ROS). Mitochondria, the major producers of ROS, exhibit impaired structure and function in COPD, resulting in reduced oxidative capacity and excessive ROS production. Antioxidants have been shown to protect against ROS-induced oxidative damage in COPD, by reducing ROS levels, reducing inflammation, and protecting against the development of emphysema. However, currently available antioxidants are not routinely used in the management of COPD, suggesting the need for more effective antioxidant agents. In recent years, a number of mitochondria-targeted antioxidant (MTA) compounds have been developed that are capable of crossing the mitochondria lipid bilayer, offering a more targeted approach to reducing ROS at its source. In particular, MTAs have been shown to illicit greater protective effects compared to non-targeted, cellular antioxidants by further reducing apoptosis and offering greater protection against mtDNA damage, suggesting they are promising therapeutic agents for the treatment of COPD. Here, we review evidence for the therapeutic potential of MTAs as a treatment for chronic lung disease and discuss current challenges and future directions. Full article
(This article belongs to the Special Issue Oxidative Stress in Chronic Obstructive Pulmonary Disease)
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21 pages, 2850 KiB  
Article
Synergistic Combination of Citrus Flavanones as Strong Antioxidant and COX-Inhibitor Agent
by Antonella Smeriglio, Nunzio Iraci, Marcella Denaro, Giuseppina Mandalari, Salvatore Vincenzo Giofrè and Domenico Trombetta
Antioxidants 2023, 12(4), 972; https://doi.org/10.3390/antiox12040972 - 21 Apr 2023
Cited by 2 | Viewed by 1523
Abstract
Recently, we demonstrated that a Citrus flavanone mix (FM) shows antioxidant and anti-inflammatory activity, even after gastro-duodenal digestion (DFM). The aim of this study was to investigate the possible involvement of the cyclooxygenases (COXs) in the anti-inflammatory activity previously detected, using a human [...] Read more.
Recently, we demonstrated that a Citrus flavanone mix (FM) shows antioxidant and anti-inflammatory activity, even after gastro-duodenal digestion (DFM). The aim of this study was to investigate the possible involvement of the cyclooxygenases (COXs) in the anti-inflammatory activity previously detected, using a human COX inhibitor screening assay, molecular modeling studies, and PGE2 release by Caco-2 cells stimulated with IL-1β and arachidonic acid. Furthermore, the ability to counteract pro-oxidative processes induced by IL-1β was evaluated by measuring four oxidative stress markers, namely, carbonylated proteins, thiobarbituric acid-reactive substances, reactive oxygen species, and reduced glutathione/oxidized glutathione ratio in Caco-2 cells. All flavonoids showed a strong inhibitory activity on COXs, confirmed by molecular modeling studies, with DFM, which showed the best and most synergistic activity on COX-2 (82.45% vs. 87.93% of nimesulide). These results were also corroborated by the cell-based assays. Indeed, DFM proves to be the most powerful anti-inflammatory and antioxidant agent reducing, synergistically and in a statistically significant manner (p < 0.05), PGE2 release than the oxidative stress markers, also with respect to the nimesulide and trolox used as reference compounds. This leads to the hypothesis that FM could be an excellent antioxidant and COX inhibitor candidate to counteract intestinal inflammation. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation as Targets for Novel Preventive and Therapeutic Approaches in Non-Communicable Diseases III)
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15 pages, 4130 KiB  
Article
Low-Dose Acetylsalicylic Acid and Mitochondria-Targeted Antioxidant Mitoquinone Attenuate Non-Alcoholic Steatohepatitis in Mice
by Saadet Turkseven, Cristian Turato, Gianmarco Villano, Mariagrazia Ruvoletto, Maria Guido, Massimo Bolognesi, Patrizia Pontisso and Marco Di Pascoli
Antioxidants 2023, 12(4), 971; https://doi.org/10.3390/antiox12040971 - 21 Apr 2023
Cited by 2 | Viewed by 1460
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. NAFLD can evolve from simple fatty liver to non-alcoholic steatohepatitis (NASH), and ultimately, to cirrhosis. Inflammation and oxidative stress, promoted by mitochondrial dysfunction, play a crucial role in the onset and [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. NAFLD can evolve from simple fatty liver to non-alcoholic steatohepatitis (NASH), and ultimately, to cirrhosis. Inflammation and oxidative stress, promoted by mitochondrial dysfunction, play a crucial role in the onset and development of NASH. To date, no therapy has been approved for NAFLD and NASH. The aim of this study is to evaluate if the anti-inflammatory activity of acetylsalicylic acid (ASA) and the mitochondria-targeted antioxidant effect of mitoquinone could hinder the progression of non-alcoholic steatohepatitis. In mice, fatty liver was induced through the administration of a deficient in methionine and choline and rich in fat diet. Two experimental groups were treated orally with ASA or mitoquinone. Histopathologic evaluation of steatosis and inflammation was performed; the hepatic expression of genes associated with inflammation, oxidative stress, and fibrosis was evaluated; the protein expression of IL-10, cyclooxygenase 2, superoxide dismutase 1, and glutathione peroxidase 1 in the liver was analyzed; a quantitative analysis of 15-epi-lipoxin A4 in liver homogenates was performed. Mitoquinone and ASA significantly reduced liver steatosis and inflammation by decreasing the expression of TNFα, IL-6, Serpinb3, and cyclooxygenase 1 and 2 and restoring the anti-inflammatory IL-10. Treatment with mitoquinone and ASA increased the gene and protein expression of antioxidants, i.e., catalase, superoxide dismutase 1, and glutathione peroxidase 1, and decreased the expression of profibrogenic genes. ASA normalized the levels of 15-epi-Lipoxin A4. In mice fed with a deficient in methionine and choline and rich in fat diet, mitoquinone and ASA reduce steatosis and necroinflammation and may represent two effective novel strategies for the treatment of non-alcoholic steatohepatitis. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases - 2nd Edition)
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18 pages, 3539 KiB  
Article
Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia
by Diego Romero-Miguel, Marta Casquero-Veiga, Javier Fernández, Nicolás Lamanna-Rama, Vanessa Gómez-Rangel, Carlos Gálvez-Robleño, Cristina Santa-Marta, Claudio J. Villar, Felipe Lombó, Raquel Abalo, Manuel Desco and María Luisa Soto-Montenegro
Antioxidants 2023, 12(4), 970; https://doi.org/10.3390/antiox12040970 - 20 Apr 2023
Cited by 1 | Viewed by 1980
Abstract
The microbiota-gut-brain axis is a complex interconnected system altered in schizophrenia. The antioxidant N-acetylcysteine (NAC) has been proposed as an adjunctive therapy to antipsychotics in clinical trials, but its role in the microbiota-gut-brain axis has not been sufficiently explored. We aimed to describe [...] Read more.
The microbiota-gut-brain axis is a complex interconnected system altered in schizophrenia. The antioxidant N-acetylcysteine (NAC) has been proposed as an adjunctive therapy to antipsychotics in clinical trials, but its role in the microbiota-gut-brain axis has not been sufficiently explored. We aimed to describe the effect of NAC administration during pregnancy on the gut-brain axis in the offspring from the maternal immune stimulation (MIS) animal model of schizophrenia. Pregnant Wistar rats were treated with PolyI:C/Saline. Six groups of animals were studied according to the study factors: phenotype (Saline, MIS) and treatment (no NAC, NAC 7 days, NAC 21 days). Offspring were subjected to the novel object recognition test and were scanned using MRI. Caecum contents were used for metagenomics 16S rRNA sequencing. NAC treatment prevented hippocampal volume reduction and long-term memory deficits in MIS-offspring. In addition, MIS-animals showed lower bacterial richness, which was prevented by NAC. Moreover, NAC7/NAC21 treatments resulted in a reduction of proinflammatory taxons in MIS-animals and an increase in taxa known to produce anti-inflammatory metabolites. Early approaches, like this one, with anti-inflammatory/anti-oxidative compounds, especially in neurodevelopmental disorders with an inflammatory/oxidative basis, may be useful in modulating bacterial microbiota, hippocampal size, as well as hippocampal-based memory impairments. Full article
(This article belongs to the Special Issue The Role of Natural Antioxidants in Neuroinflammation)
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19 pages, 4338 KiB  
Article
Epigallocatechin-3-Gallate Attenuates Leukocyte Infiltration in 67-kDa Laminin Receptor-Dependent and -Independent Pathways in the Rat Frontoparietal Cortex following Status Epilepticus
by Ji-Eun Kim, Duk-Shin Lee and Tae-Cheon Kang
Antioxidants 2023, 12(4), 969; https://doi.org/10.3390/antiox12040969 - 20 Apr 2023
Viewed by 1257
Abstract
Status epilepticus (SE) evokes leukocyte infiltration in the frontoparietal cortex (FPC) without the blood-brain barrier disruption. Monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) regulate leukocyte recruitments into the brain parenchyma. Epigallocatechin-3-gallate (EGCG) is an antioxidant and a ligand for non-integrin 67-kDa [...] Read more.
Status epilepticus (SE) evokes leukocyte infiltration in the frontoparietal cortex (FPC) without the blood-brain barrier disruption. Monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) regulate leukocyte recruitments into the brain parenchyma. Epigallocatechin-3-gallate (EGCG) is an antioxidant and a ligand for non-integrin 67-kDa laminin receptor (67LR). However, it is unknown whether EGCG and/or 67LR affect SE-induced leukocyte infiltrations in the FPC. In the present study, SE infiltrated myeloperoxidase (MPO)-positive neutrophils, as well as cluster of differentiation 68 (CD68)-positive monocytes in the FPC are investigated. Following SE, MCP-1 was upregulated in microglia, which was abrogated by EGCG treatment. The C–C motif chemokine receptor 2 (CCR2, MCP-1 receptor) and MIP-2 expressions were increased in astrocytes, which were attenuated by MCP-1 neutralization and EGCG treatment. SE reduced 67LR expression in astrocytes, but not endothelial cells. Under physiological conditions, 67LR neutralization did not lead to MCP-1 induction in microglia. However, it induced MIP-2 expression and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in astrocytes and leukocyte infiltration in the FPC. Co-treatment of EGCG or U0126 (an ERK1/2 inhibitor) attenuated these events induced by 67LR neutralization. These findings indicate that the EGCG may ameliorate leukocyte infiltration in the FPC by inhibiting microglial MCP-1 induction independent of 67LR, as well as 67LR-ERK1/2-MIP-2 signaling pathway in astrocytes. Full article
(This article belongs to the Special Issue Inhibition of Oxidative Stress and Related Signaling Pathways in Neuroprotection)
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21 pages, 4701 KiB  
Article
Protective Effect of Lonicera japonica on PM2.5-Induced Pulmonary Damage in BALB/c Mice via the TGF-β and NF-κB Pathway
by Hyo Lim Lee, Jong Min Kim, Min Ji Go, Tae Yoon Kim, Seung Gyum Joo, Ju Hui Kim, Han Su Lee, Hyun-Jin Kim and Ho Jin Heo
Antioxidants 2023, 12(4), 968; https://doi.org/10.3390/antiox12040968 - 20 Apr 2023
Cited by 4 | Viewed by 1816
Abstract
This study aimed to assess the protective effect of an extract of Lonicera japonica against particulate-matter (PM)2.5-induced pulmonary inflammation and fibrosis. The compounds with physiological activity were identified as shanzhiside, secologanoside, loganic acid, chlorogenic acid, secologanic acid, secoxyloganin, quercetin pentoside, and [...] Read more.
This study aimed to assess the protective effect of an extract of Lonicera japonica against particulate-matter (PM)2.5-induced pulmonary inflammation and fibrosis. The compounds with physiological activity were identified as shanzhiside, secologanoside, loganic acid, chlorogenic acid, secologanic acid, secoxyloganin, quercetin pentoside, and dicaffeoyl quinic acids (DCQA), including 3,4-DCQA, 3,5-DCQA, 4,5-DCQA, and 1,4-DCQA using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). The extract of Lonicera japonica reduced cell death, reactive oxygen species (ROS) production, and inflammation in A549 cells. The extract of Lonicera japonica decreased serum T cells, including CD4+ T cells, CD8+ T cells, and total T helper 2 (Th2) cells, and immunoglobulins, including immunoglobulin G (IgG) and immunoglobulin E (IgE), in PM2.5-induced BALB/c mice. The extract of Lonicera japonica protected the pulmonary antioxidant system by regulating superoxide dismutase (SOD) activity, reduced glutathione (GSH) contents, and malondialdehyde (MDA) levels. In addition, it ameliorated mitochondrial function by regulating the production of ROS, mitochondrial membrane potential (MMP), and ATP contents. Moreover, the extract of Lonicera japonica exhibited a protective activity of apoptosis, fibrosis, and matrix metalloproteinases (MMPs) via TGF-β and NF-κB signaling pathways in lung tissues. This study suggests that the extract of Lonicera japonica might be a potential material to improve PM2.5-induced pulmonary inflammation, apoptosis, and fibrosis. Full article
(This article belongs to the Special Issue Oxidative Stress and Lung Inflammation)
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27 pages, 2923 KiB  
Review
Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?
by Lei Li, Peilan Peng, Ning Ding, Wenhui Jia, Canhua Huang and Yong Tang
Antioxidants 2023, 12(4), 967; https://doi.org/10.3390/antiox12040967 - 20 Apr 2023
Cited by 15 | Viewed by 4682
Abstract
Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD [...] Read more.
Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD by regulating the homeostasis of the gut microbiota and immune response. Therefore, redox-targeted therapy is a promising treatment option for IBD. Recent evidence has verified that Chinese herbal medicine (CHM)-derived polyphenols, natural antioxidants, are able to maintain redox equilibrium in the intestinal tract to prevent abnormal gut microbiota and radical inflammatory responses. Here, we provide a comprehensive perspective for implementing natural antioxidants as potential IBD candidate medications. In addition, we demonstrate novel technologies and stratagems for promoting the antioxidative properties of CHM-derived polyphenols, including novel delivery systems, chemical modifications, and combination strategies. Full article
(This article belongs to the Special Issue Reactive Oxygen Species (ROS) in Gastrointestinal Diseases)
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20 pages, 12226 KiB  
Article
EGCG Attenuates CA1 Neuronal Death by Regulating GPx1, NF-κB S536 Phosphorylation and Mitochondrial Dynamics in the Rat Hippocampus following Status Epilepticus
by Ji-Eun Kim, Tae-Hyun Kim and Tae-Cheon Kang
Antioxidants 2023, 12(4), 966; https://doi.org/10.3390/antiox12040966 - 20 Apr 2023
Cited by 1 | Viewed by 1362
Abstract
Epigallocatechin-3-gallate (EGCG) is an antioxidant that directly scavenges reactive oxygen species (ROS) and inhibits pro-oxidant enzymes. Although EGCG protects hippocampal neurons from status epilepticus (SE, a prolonged seizure activity), the underlying mechanisms are not fully understood. As the preservation of mitochondrial dynamics is [...] Read more.
Epigallocatechin-3-gallate (EGCG) is an antioxidant that directly scavenges reactive oxygen species (ROS) and inhibits pro-oxidant enzymes. Although EGCG protects hippocampal neurons from status epilepticus (SE, a prolonged seizure activity), the underlying mechanisms are not fully understood. As the preservation of mitochondrial dynamics is essential for cell viability, it is noteworthy to elucidate the effects of EGCG on impaired mitochondrial dynamics and the related signaling pathways in SE-induced CA1 neuronal degeneration, which are yet unclear. In the present study, we found that EGCG attenuated SE-induced CA1 neuronal death, accompanied by glutathione peroxidase-1 (GPx1) induction. EGCG also abrogated mitochondrial hyperfusion in these neurons by the preservation of extracellular signal-regulated kinase 1/2 (ERK1/2)–dynamin-related protein 1 (DRP1)-mediated mitochondrial fission, independent of c-Jun N-terminal kinase (JNK) activity. Furthermore, EGCG abolished SE-induced nuclear factor-κB (NF-κB) serine (S) 536 phosphorylation in CA1 neurons. ERK1/2 inhibition by U0126 diminished the effect of EGCG on neuroprotection and mitochondrial hyperfusion in response to SE without affecting GPx1 induction and NF-κB S536 phosphorylation, indicating that the restoration of ERK1/2–DRP1-mediated fission may be required for the neuroprotective effects of EGCG against SE. Therefore, our findings suggest that EGCG may protect CA1 neurons from SE insults through GPx1–ERK1/2–DRP1 and GPx1–NF-κB signaling pathways, respectively. Full article
(This article belongs to the Special Issue Cellular ROS and Antioxidants: Physiological and Pathological Role)
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34 pages, 1855 KiB  
Review
Redox Imbalance in Neurological Disorders in Adults and Children
by Federica Rey, Clarissa Berardo, Erika Maghraby, Alessia Mauri, Letizia Messa, Letizia Esposito, Giovanna Casili, Sara Ottolenghi, Eleonora Bonaventura, Salvatore Cuzzocrea, Gianvincenzo Zuccotti, Davide Tonduti, Emanuela Esposito, Irene Paterniti, Cristina Cereda and Stephana Carelli
Antioxidants 2023, 12(4), 965; https://doi.org/10.3390/antiox12040965 - 20 Apr 2023
Cited by 3 | Viewed by 3637
Abstract
Oxygen is a central molecule for numerous metabolic and cytophysiological processes, and, indeed, its imbalance can lead to numerous pathological consequences. In the human body, the brain is an aerobic organ and for this reason, it is very sensitive to oxygen equilibrium. The [...] Read more.
Oxygen is a central molecule for numerous metabolic and cytophysiological processes, and, indeed, its imbalance can lead to numerous pathological consequences. In the human body, the brain is an aerobic organ and for this reason, it is very sensitive to oxygen equilibrium. The consequences of oxygen imbalance are especially devastating when occurring in this organ. Indeed, oxygen imbalance can lead to hypoxia, hyperoxia, protein misfolding, mitochondria dysfunction, alterations in heme metabolism and neuroinflammation. Consequently, these dysfunctions can cause numerous neurological alterations, both in the pediatric life and in the adult ages. These disorders share numerous common pathways, most of which are consequent to redox imbalance. In this review, we will focus on the dysfunctions present in neurodegenerative disorders (specifically Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis) and pediatric neurological disorders (X-adrenoleukodystrophies, spinal muscular atrophy, mucopolysaccharidoses and Pelizaeus–Merzbacher Disease), highlighting their underlining dysfunction in redox and identifying potential therapeutic strategies. Full article
(This article belongs to the Special Issue Redox Signaling Regulation in Neurological Disorders)
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13 pages, 1212 KiB  
Article
CoQ10Phytosomes Improve Cellular Ubiquinone Uptake in Skeletal Muscle Cells: An Ex Vivo Study Using CoQ10-Enriched Low-Density Lipoproteins Obtained in a Randomized Crossover Study
by Fabio Marcheggiani, Patrick Orlando, Sonia Silvestri, Ilenia Cirilli, Antonella Riva, Giovanna Petrangolini, Francesca Orsini and Luca Tiano
Antioxidants 2023, 12(4), 964; https://doi.org/10.3390/antiox12040964 - 20 Apr 2023
Viewed by 1561
Abstract
Coenzyme Q10 (CoQ10) bioavailability in vivo is limited due to its lipophilic nature. Moreover, a large body of evidence in the literature shows that muscle CoQ10 uptake is limited. In order to address cell specific differences in CoQ uptake, [...] Read more.
Coenzyme Q10 (CoQ10) bioavailability in vivo is limited due to its lipophilic nature. Moreover, a large body of evidence in the literature shows that muscle CoQ10 uptake is limited. In order to address cell specific differences in CoQ uptake, we compared cellular CoQ10 content in cultured human dermal fibroblasts and murine skeletal muscle cells that were incubated with lipoproteins from healthy volunteers and enriched with different formulations of CoQ10 following oral supplementation. Using a crossover design, eight volunteers were randomized to supplement 100 mg/daily CoQ10 for two weeks, delivered both in phytosome form (UBQ) as a lecithin formulation and in CoQ10 crystalline form. After supplementation, plasma was collected for CoQ10 determination. In the same samples, low density lipoproteins (LDL) were extracted and normalized for CoQ10 content, and 0.5 µg/mL in the medium were incubated with the two cell lines for 24 h. The results show that while both formulations were substantially equivalent in terms of plasma bioavailability in vivo, UBQ-enriched lipoproteins showed a higher bioavailability compared with crystalline CoQ10-enriched ones both in human dermal fibroblasts (+103%) and in murine skeletal myoblasts (+48%). Our data suggest that phytosome carriers might provide a specific advantage in delivering CoQ10 to skin and muscle tissues. Full article
(This article belongs to the Special Issue The Ubiquitous and Multifaceted Coenzyme Q)
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12 pages, 3297 KiB  
Article
Human Microglia Synthesize Neurosteroids to Cope with Rotenone-Induced Oxidative Stress
by Chiara Lucchi, Alessandro Codeluppi, Monica Filaferro, Giovanni Vitale, Cecilia Rustichelli, Rossella Avallone, Jessica Mandrioli and Giuseppe Biagini
Antioxidants 2023, 12(4), 963; https://doi.org/10.3390/antiox12040963 - 19 Apr 2023
Cited by 3 | Viewed by 1350
Abstract
We obtained evidence that mouse BV2 microglia synthesize neurosteroids dynamically to modify neurosteroid levels in response to oxidative damage caused by rotenone. Here, we evaluated whether neurosteroids could be produced and altered in response to rotenone by the human microglial clone 3 (HMC3) [...] Read more.
We obtained evidence that mouse BV2 microglia synthesize neurosteroids dynamically to modify neurosteroid levels in response to oxidative damage caused by rotenone. Here, we evaluated whether neurosteroids could be produced and altered in response to rotenone by the human microglial clone 3 (HMC3) cell line. To this aim, HMC3 cultures were exposed to rotenone (100 nM) and neurosteroids were measured in the culture medium by liquid chromatography with tandem mass spectrometry. Microglia reactivity was evaluated by measuring interleukin 6 (IL-6) levels, whereas cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. After 24 h (h), rotenone increased IL-6 and reactive oxygen species levels by approximately +37% over the baseline, without affecting cell viability; however, microglia viability was significantly reduced at 48 h (p < 0.01). These changes were accompanied by the downregulation of several neurosteroids, including pregnenolone, pregnenolone sulfate, 5α-dihydroprogesterone, and pregnanolone, except for allopregnanolone, which instead was remarkably increased (p < 0.05). Interestingly, treatment with exogenous allopregnanolone (1 nM) efficiently prevented the reduction in HMC3 cell viability. In conclusion, this is the first evidence that human microglia can produce allopregnanolone and that this neurosteroid is increasingly released in response to oxidative stress, to tentatively support the microglia’s survival. Full article
(This article belongs to the Special Issue Oxidative Stress in Brain Function)
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27 pages, 12080 KiB  
Article
Influence of Storage Conditions on Stability of Phenolic Compounds and Antioxidant Activity Values in Nutraceutical Mixtures with Edible Flowers as New Dietary Supplements
by Martina Mrázková, Daniela Sumczynski and Jana Orsavová
Antioxidants 2023, 12(4), 962; https://doi.org/10.3390/antiox12040962 - 19 Apr 2023
Cited by 1 | Viewed by 2132
Abstract
This paper investigates the effects of storage conditions on the stability of phenolics and their antioxidant activities in unique nutraceutical supplements containing non-traditional cereal flakes, edible flowers, fruits, nuts, and seeds. Significant total phenolic content (TPC) of 1170–2430 mg GAE/kg and total anthocyanin [...] Read more.
This paper investigates the effects of storage conditions on the stability of phenolics and their antioxidant activities in unique nutraceutical supplements containing non-traditional cereal flakes, edible flowers, fruits, nuts, and seeds. Significant total phenolic content (TPC) of 1170–2430 mg GAE/kg and total anthocyanin content (TAC) with the values of 322–663 mg C3G/kg were determined with the highest TPC content established in free phenolic fractions. The most notable declines in TPC (by 53%), TAC (by 62%), phenolics (e.g., glycosylated anthocyanins by 35–67%), and antioxidant activity (by 25% using DPPH) were established in the presence of sunlight at 23 °C followed by the storage at 40 °C. Quercetin, rutin, peonidin, pelargonidin, p-coumaric, ellagic, and p-hydroxybenzoic acids were identified as the least stable phenolics when exposed to sunlight. Furthermore, glycosylated forms of anthocyanins demonstrated a greater stability when compared with anthocyanidins. The mixtures considerably eliminated ABTS and DPPH radicals. In all samples, water-soluble substances showed a higher antioxidant activity than lipid-soluble substances with the main contributors in the following order: delphinidin-3-glucoside (r = +0.9839) > p-coumaric > gallic > sinapic > p-hydroxybenzoic acids > delphinidin > peonidin and malvidin (r = +0.6538). Gluten-free nutraceutical mixtures M3 (containing red rice and black quinoa flakes, red and blue cornflowers, blueberries, and barberries) and M4 (containing red and black rice flakes, rose, blue cornflower, blueberries, raspberries, and barberries) were evaluated as the least stable under all storage conditions although they showed considerable phenolic concentrations. Phenolic contents and antioxidant activity of the nutraceutical mixtures were the highest at 23 °C without the presence of sunlight with the most stable M1 nutraceutical mixture (containing oat and red wheat flakes, hibiscus, lavender, blueberries, raspberries, and barberries). Full article
(This article belongs to the Special Issue Dietary Supplements and Oxidative Stress)
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14 pages, 1751 KiB  
Article
Distinct Effects of Seed Coat and Flower Colors on Metabolite Contents and Antioxidant Activities in Safflower Seeds
by Weilan Li, Eunae Yoo, Jungsook Sung, Sookyeong Lee, Sojeong Hwang and Gi-An Lee
Antioxidants 2023, 12(4), 961; https://doi.org/10.3390/antiox12040961 - 19 Apr 2023
Cited by 1 | Viewed by 1527
Abstract
Safflower is an important oilseed crop cultivated primarily for its seeds, which have pharmaceutical properties. Color is an important agronomical trait that appears to be a prior parameter for evaluating the internal quality of plant seeds. This study employs 197 safflower accessions seeds [...] Read more.
Safflower is an important oilseed crop cultivated primarily for its seeds, which have pharmaceutical properties. Color is an important agronomical trait that appears to be a prior parameter for evaluating the internal quality of plant seeds. This study employs 197 safflower accessions seeds to analyze how their seed coat and flower colors affect their total oil content, fatty acid composition, total phenolic content (TPC), N-(p-coumaroyl)serotonin (CS) and N-feruloylserotonin (FS) contents, and [2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)] radical scavenging activities. Significant variations were observed in the targeted metabolite contents and antioxidant properties among genotypes. Notably, the linoleic acid content, total unsaturated fatty acid content, the ratio of total unsaturated fatty acid to total saturated fatty acid, CS, FS, ABTS, and DPPH scavenging capacities varied significantly based on seed coat color, with white-seeded genotypes having the highest average values of these parameters. Moreover, the linoleic acid content differed significantly (p < 0.05) among the genotypes with varying flower colors, with white-flowered accessions having the highest average content. Furthermore, genotypes K185105 (No. 75) and K175278 (No. 146) were identified as promising genetic resources with health benefits. Overall, these findings reveal that seed coat and flower colors distinctly affect metabolite contents and antioxidant properties in safflower seeds. Full article
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16 pages, 2387 KiB  
Article
Colchicine Protects against Ethanol-Induced Senescence and Senescence-Associated Secretory Phenotype in Endothelial Cells
by Huakang Zhou, Dilaware Khan, Norbert Gerdes, Carsten Hagenbeck, Majeed Rana, Jan Frederick Cornelius and Sajjad Muhammad
Antioxidants 2023, 12(4), 960; https://doi.org/10.3390/antiox12040960 - 19 Apr 2023
Cited by 5 | Viewed by 2237
Abstract
Inflammaging is a potential risk factor for cardiovascular diseases. It results in the development of thrombosis and atherosclerosis. The accumulation of senescent cells in vessels causes vascular inflammaging and contributes to plaque formation and rupture. In addition to being an acquired risk factor [...] Read more.
Inflammaging is a potential risk factor for cardiovascular diseases. It results in the development of thrombosis and atherosclerosis. The accumulation of senescent cells in vessels causes vascular inflammaging and contributes to plaque formation and rupture. In addition to being an acquired risk factor for cardiovascular diseases, ethanol can induce inflammation and senescence, both of which have been implicated in cardiovascular diseases. In the current study, we used colchicine to abate the cellular damaging effects of ethanol on endothelial cells. Colchicine prevented senescence and averted oxidative stress in endothelial cells exposed to ethanol. It lowered the relative protein expression of aging and senescence marker P21 and restored expression of the DNA repair proteins KU70/KU80. Colchicine inhibited the activation of nuclear factor kappa B (NFκ-B) and mitogen activated protein kinases (MAPKs) in ethanol-treated endothelial cells. It reduced ethanol-induced senescence-associated secretory phenotype. In summary, we show that colchicine ameliorated the ethanol-caused molecular events, resulting in attenuated senescence and senescence-associated secretory phenotype in endothelial cells. Full article
(This article belongs to the Special Issue Alcohol-Induced Oxidative Stress in Health and Disease)
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19 pages, 1618 KiB  
Review
Impaired Melatonin Secretion, Oxidative Stress and Metabolic Syndrome in Night Shift Work
by Sorina Hohor, Cristina Mandanach, Andreea Maftei, Corina Aurelia Zugravu and Marina Ruxandra Oțelea
Antioxidants 2023, 12(4), 959; https://doi.org/10.3390/antiox12040959 - 19 Apr 2023
Cited by 3 | Viewed by 2163
Abstract
Metabolic syndrome has been associated in many studies with working in shifts. Even if the mechanistic details are not fully understood, forced sleep deprivation and exposure to light, as happens during night shifts, or irregular schedules with late or very early onset of [...] Read more.
Metabolic syndrome has been associated in many studies with working in shifts. Even if the mechanistic details are not fully understood, forced sleep deprivation and exposure to light, as happens during night shifts, or irregular schedules with late or very early onset of the working program, lead to a sleep–wake rhythm misalignment, metabolic dysregulation and oxidative stress. The cyclic melatonin secretion is regulated by the hypothalamic suprachiasmatic nuclei and light exposure. At a central level, melatonin promotes sleep and inhibits wake-signals. Beside this role, melatonin acts as an antioxidant and influences the functionality of the cardiovascular system and of different metabolic processes. This review presents data about the influence of night shifts on melatonin secretion and oxidative stress. Assembling data from epidemiological, experimental and clinical studies contributes to a better understanding of the pathological links between chronodisruption and the metabolic syndrome related to working in shifts. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Metabolic Syndrome)
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12 pages, 630 KiB  
Article
Low Grade Endotoxemia and Oxidative Stress in Offspring of Patients with Early Myocardial Infarction
by Bianca Laura Cinicola, Ilaria Maria Palumbo, Arianna Pannunzio, Roberto Carnevale, Simona Bartimoccia, Vittoria Cammisotto, Martina Capponi, Giulia Brindisi, Francesca Salvatori, Francesco Barillà, Francesco Martino, Alessandra D’Amico, Roberto Poscia, Alberto Spalice, Anna Maria Zicari, Francesco Violi and Lorenzo Loffredo
Antioxidants 2023, 12(4), 958; https://doi.org/10.3390/antiox12040958 - 19 Apr 2023
Cited by 2 | Viewed by 1419
Abstract
Background and aims: Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets [...] Read more.
Background and aims: Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets in these patients. Furthermore, altered intestinal permeability and serum lipopolysaccharide (LPS) could be a trigger to promote NOX-2 activation and platelet aggregation. This study aims to evaluate the behavior of low grade endotoxemia, oxidative stress and platelet activation in offspring of patients with early myocardial infarction. Methods: We enrolled, in a cross-sectional study, 46 offspring of patients with early myocardial infarction and 86 healthy subjects (HS). LPS levels and gut permeability (assessed by zonulin), oxidative stress (assessed by serum NOX-2-derived peptide (sNOX2-dp) release, hydrogen peroxide (H2O2) production and isoprostanes), serum nitric oxide (NO) bioavailability and platelet activation (by serum thromboxane B2 (TXB2) and soluble P-Selectin (sP-Selectin)) were analyzed. Results: Compared to HS, offspring of patients with early myocardial infarction had higher values of LPS, zonulin, serum isoprostanes, sNOX2-dp H2O2, TXB2, p-selectin and lower NO bioavailability. Logistic regression analysis showed that the variables associated with offspring of patients with early myocardial infarction were LPS, TXB2 and isoprostanes. The multiple linear regression analysis confirmed that serum NOX-2, isoprostanes, p-selectin and H2O2 levels were significantly associated to LPS. Furthermore, serum LPS, isoprostanes and TXB2 levels were significantly associated with sNOX-2-dp. Conclusions: Offspring of patients with early myocardial infarction have a low grade endotoxemia that could generate oxidative stress and platelet activation increasing their cardiovascular risk. Future studies are needed to understand the role of dysbiosis in this population. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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13 pages, 860 KiB  
Article
Valorization of Grape Pomace as a Renewable Source of Techno-Functional and Antioxidant Pectins
by Roberto Megías-Pérez, Alvaro Ferreira-Lazarte and Mar Villamiel
Antioxidants 2023, 12(4), 957; https://doi.org/10.3390/antiox12040957 - 19 Apr 2023
Cited by 6 | Viewed by 1490
Abstract
The food industry’s increasing demand for new functional ingredients that meet both organoleptic and healthy requirements has driven the exploration of new sources of functional ingredients in agro-industrial by-products. The aim of this work was to valorize grape pomace (Vitis vinifera L. [...] Read more.
The food industry’s increasing demand for new functional ingredients that meet both organoleptic and healthy requirements has driven the exploration of new sources of functional ingredients in agro-industrial by-products. The aim of this work was to valorize grape pomace (Vitis vinifera L. garnacha) as a source of pectins using food-grade extracting agents. Obtained pectins were evaluated for monomeric composition, methyl esterification, molecular weight, water retention, oil-holding capacity, and antioxidant properties. The relatively soft extraction conditions used permitted obtaining low methoxyl pectin (10–42%) enriched in homogalacturonan (38–45%) or rhamnogalacturonan (33–41%) with different branching degrees, molecular weight, and fewer impurities than those found in the scarce previous literature. The relationship between structure and functionality was studied. Among the different pectins obtained, the sample derived from the extraction with sodium citrate could resume the best characteristics, such as pectin purity and higher water retention and oil holding capacity. These results underscore the relevance of grape pomace as a viable alternative source of pectin. Full article
(This article belongs to the Special Issue Antioxidant Foods and Cardiometabolic Health - 2nd Edition)
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20 pages, 3825 KiB  
Article
Influence of Increased Radiation Background on Antioxidative Responses of Helianthus tuberosus L.
by Oksana B. Polivanova, Kirill N. Tiurin, Anastasia B. Sivolapova, Svetlana V. Goryunova and Sergey V. Zhevora
Antioxidants 2023, 12(4), 956; https://doi.org/10.3390/antiox12040956 - 18 Apr 2023
Cited by 2 | Viewed by 1215
Abstract
As a result of the accident at the Chornobyl Nuclear Power Plant, significant territories were exposed to ionizing radiation. Some isotopes, such as 137Cs, are capable of making a significant impact on living organisms in the long-term perspective. The generation of reactive [...] Read more.
As a result of the accident at the Chornobyl Nuclear Power Plant, significant territories were exposed to ionizing radiation. Some isotopes, such as 137Cs, are capable of making a significant impact on living organisms in the long-term perspective. The generation of reactive oxygen species is one mechanism by which ionizing radiation affects living organisms, initiating mechanisms of antioxidant protection. In this article, the effect of increased ionizing radiation on the content of non–enzymatic antioxidants and the activity of antioxidant defense enzymes of Helianthus tuberosum L. was studied. This plant is widely distributed in Europe and characterized by high adaptability to abiotic factors. We found that the activity of antioxidant defense enzymes, such as catalase and peroxidase, weakly correlated with radiation exposure. The activity of ascorbate peroxidase, on the contrary, is strongly positively correlated with radiation exposure. The samples growing on the territory with constant low exposure to ionizing radiation were also characterized by an increased concentration of ascorbic acid and water-soluble phenolic compounds compared to the controls. This study may be useful for understanding the mechanisms underlying the adaptive reactions of plants under prolonged exposure to ionizing radiation. Full article
(This article belongs to the Special Issue Antioxidant Mechanisms in Plants)
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14 pages, 887 KiB  
Review
Oxidative Stress and Neuroinflammation in Parkinson’s Disease: The Role of Dopamine Oxidation Products
by Sasanka Chakrabarti and Marco Bisaglia
Antioxidants 2023, 12(4), 955; https://doi.org/10.3390/antiox12040955 - 18 Apr 2023
Cited by 6 | Viewed by 1996
Abstract
Parkinson’s disease (PD) is a chronic neurodegenerative condition affecting more than 1% of people over 65 years old. It is characterized by the preferential degeneration of nigrostriatal dopaminergic neurons, which is responsible for the motor symptoms of PD patients. The pathogenesis of this [...] Read more.
Parkinson’s disease (PD) is a chronic neurodegenerative condition affecting more than 1% of people over 65 years old. It is characterized by the preferential degeneration of nigrostriatal dopaminergic neurons, which is responsible for the motor symptoms of PD patients. The pathogenesis of this multifactorial disorder is still elusive, hampering the discovery of therapeutic strategies able to suppress the disease’s progression. While redox alterations, mitochondrial dysfunctions, and neuroinflammation are clearly involved in PD pathology, how these processes lead to the preferential degeneration of dopaminergic neurons is still an unanswered question. In this context, the presence of dopamine itself within this neuronal population could represent a crucial determinant. In the present review, an attempt is made to link the aforementioned pathways to the oxidation chemistry of dopamine, leading to the formation of free radical species, reactive quinones and toxic metabolites, and sustaining a pathological vicious cycle. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Movement Disorders)
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15 pages, 2913 KiB  
Article
Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment
by Paula Aranda-Martínez, José Fernández-Martínez, Yolanda Ramírez-Casas, César Rodríguez-Santana, Iryna Rusanova, Germaine Escames and Darío Acuña-Castroviejo
Antioxidants 2023, 12(4), 954; https://doi.org/10.3390/antiox12040954 - 18 Apr 2023
Cited by 4 | Viewed by 1606
Abstract
Beyond sleep/wake, clock genes regulate the daily rhythms of melatonin production, motor activity, innate immunity, and mitochondrial dynamics, among others. All these rhythms are affected in Parkinson’s disease (PD), suggesting that chronodisruption may be an early stage of the disease. The aim of [...] Read more.
Beyond sleep/wake, clock genes regulate the daily rhythms of melatonin production, motor activity, innate immunity, and mitochondrial dynamics, among others. All these rhythms are affected in Parkinson’s disease (PD), suggesting that chronodisruption may be an early stage of the disease. The aim of this study was to evaluate the connection between clock genes and these rhythms in PD, and whether melatonin administration reestablished the normal clock function. Parkinsonism was induced with 600 μM MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in 24–120 h post fertilization (hpf) zebrafish embryos and melatonin was administered at a dose of 1 μM. Day–night melatonin rhythm disappeared in MPTP-treated embryos, which showed an advance in the activity phase in parallel with changes in the rhythm of clock genes. An alteration in the fission-to-fusion mitochondrial dynamics was also detected in parkinsonian embryos, increasing the former and leading to apoptosis. Melatonin administration to MPTP-treated embryos fully restored the circadian system, including the rhythms of clock genes, motor activity, melatonin rhythm, and mitochondrial dynamics, and decreasing apoptosis. Because clock-controlled rhythms such as sleep/wake alterations are early events in PD, the data here reported may point to chronodisruption as one initial pathophysiological event of the disease. Full article
(This article belongs to the Special Issue Natural Antioxidants in Neurodegeneration and Aging Processes)
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16 pages, 2078 KiB  
Article
A Study on the Planarian Model Confirms the Antioxidant Properties of Tameron against X-ray- and Menadione-Induced Oxidative Stress
by Elena Tsarkova, Kristina Filippova, Vera Afanasyeva, Olga Ermakova, Anastasia Kolotova, Artem Blagodatski and Artem Ermakov
Antioxidants 2023, 12(4), 953; https://doi.org/10.3390/antiox12040953 - 18 Apr 2023
Cited by 1 | Viewed by 1456
Abstract
Ionizing radiation and radiation-related oxidative stress are two important factors responsible for the death of actively proliferating cells, thus drastically reducing the regeneration capacity of living organisms. Planarian flatworms are freshwater invertebrates that are rich in stem cells called neoblasts and, therefore, present [...] Read more.
Ionizing radiation and radiation-related oxidative stress are two important factors responsible for the death of actively proliferating cells, thus drastically reducing the regeneration capacity of living organisms. Planarian flatworms are freshwater invertebrates that are rich in stem cells called neoblasts and, therefore, present a well-established model for studies on regeneration and the testing of novel antioxidant and radioprotective substances. In this work, we tested an antiviral and antioxidant drug Tameron (Monosodium α-Luminol or 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt) for its ability to reduce the harm of X-ray- and chemically induced oxidative stress on a planarian model. Our study has revealed the ability of Tameron to effectively protect planarians from oxidative stress while enhancing their regenerative capacity by modulating the expression of neoblast marker genes and NRF-2-controlled oxidative stress response genes. Full article
(This article belongs to the Special Issue Ionizing Radiation, Antioxidant Response and Oxidative Damage: Radiomodulators)
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17 pages, 8407 KiB  
Article
Pharmacologic Comparison of High-Dose Hesperetin and Quercetin on MDCK II Cell Viability, Tight Junction Integrity, and Cell Shape
by Mio Nakashima, Natsuko Goda, Takeshi Tenno, Ayaka Kotake, Yuko Inotsume, Minako Amaya and Hidekazu Hiroaki
Antioxidants 2023, 12(4), 952; https://doi.org/10.3390/antiox12040952 - 18 Apr 2023
Cited by 2 | Viewed by 2577
Abstract
The modulation of tight junction (TJ) integrity with small molecules is important for drug delivery. High-dose baicalin (BLI), baicalein (BLE), quercetin (QUE), and hesperetin (HST) have been shown to open TJs in Madin-Darby canine kidney (MDCK) II cells, but the mechanisms for HST [...] Read more.
The modulation of tight junction (TJ) integrity with small molecules is important for drug delivery. High-dose baicalin (BLI), baicalein (BLE), quercetin (QUE), and hesperetin (HST) have been shown to open TJs in Madin-Darby canine kidney (MDCK) II cells, but the mechanisms for HST and QUE remain unclear. In this study, we compared the effects of HST and QUE on cell proliferation, morphological changes, and TJ integrity. HST and QUE were found to have opposing effects on the MDCK II cell viability, promotion, and suppression, respectively. Only QUE, but not HST, induced a morphological change in MDCK II into a slenderer cell shape. Both HST and QUE downregulated the subcellular localization of claudin (CLD)-2. However, only QUE, but not HST, downregulated CLD-2 expression. Conversely, only HST was shown to directly bind to the first PDZ domain of ZO-1, a key molecule to promote TJ biogenesis. The TGFβ pathway partially contributed to the HST-induced cell proliferation, since SB431541 ameliorated the effect. In contrast, the MEK pathway was not involved by both the flavonoids, since U0126 did not revert their TJ-opening effect. The results offer insight for using HST or QUE as naturally occurring absorption enhancers through the paracellular route. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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27 pages, 4011 KiB  
Review
Health Benefits of Antioxidant Bioactive Compounds in the Fruits and Leaves of Lonicera caerulea L. and Aronia melanocarpa (Michx.) Elliot
by Bogdan-Stefan Negreanu-Pirjol, Ovidiu Cristian Oprea, Ticuta Negreanu-Pirjol, Florentina Nicoleta Roncea, Ana-Maria Prelipcean, Oana Craciunescu, Andreea Iosageanu, Victoria Artem, Aurora Ranca, Ludmila Motelica, Anca-Cristina Lepadatu, Madalina Cosma and Dan Razvan Popoviciu
Antioxidants 2023, 12(4), 951; https://doi.org/10.3390/antiox12040951 - 18 Apr 2023
Cited by 12 | Viewed by 3593
Abstract
Lonicera caerulaea L. and Aronia melanocarpa (Michx.) Elliot fruits are frequently used for their health benefits as they are rich in bioactive compounds. They are recognized as a source of natural and valuable phytonutrients, which makes them a superfood. L. caerulea presents antioxidant [...] Read more.
Lonicera caerulaea L. and Aronia melanocarpa (Michx.) Elliot fruits are frequently used for their health benefits as they are rich in bioactive compounds. They are recognized as a source of natural and valuable phytonutrients, which makes them a superfood. L. caerulea presents antioxidant activity three to five times higher than other berries which are more commonly consumed, such as blackberries or strawberries. In addition, their ascorbic acid level is the highest among fruits. The species A. melanocarpa is considered one of the richest known sources of antioxidants, surpassing currants, cranberries, blueberries, elderberries, and gooseberries, and contains one of the highest amounts of sorbitol. The non-edible leaves of genus Aronia became more extensively analyzed as a byproduct or waste material due to their high polyphenol, flavonoid, and phenolic acid content, along with a small amount of anthocyanins, which are used as ingredients in nutraceuticals, herbal teas, bio-cosmetics, cosmeceuticals, food and by the pharmaceutical industry. These plants are a rich source of vitamins, tocopherols, folic acid, and carotenoids. However, they remain outside of mainstream fruit consumption, being well known only to a small audience. This review aims to shed light on L. caerulaea and A. melanocarpa and their bioactive compounds as healthy superfoods with antioxidant, anti-inflammatory, antitumor, antimicrobial, and anti-diabetic effects, and hepato-, cardio-, and neuro-protective potential. In this view, we hope to promote their cultivation and processing, increase their commercial availability, and also highlight the ability of these species to be used as potential nutraceutical sources, helpful for human health. Full article
(This article belongs to the Special Issue Berries in Human Health: Antioxidation, Anti-inflammation and Other Modes of Action)
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