Antioxidants

18 pages, 2715 KiB

Open AccessArticle

Loss of the Kidney Urate Transporter, Urat1, Leads to Disrupted Redox Homeostasis in Mice

by Neema Jamshidi, Kabir B. Nigam and Sanjay K. Nigam

Antioxidants 2023, 12(3), 780; https://doi.org/10.3390/antiox12030780 - 22 Mar 2023

Cited by 2 | Viewed by 1966

High uric acid is associated with gout, hypertension, metabolic syndrome, cardiovascular disease, and kidney disease. URAT1 (SLC22A12), originally discovered in mice as Rst, is generally considered a very selective uric acid transporter compared to other closely-related kidney uric acid transporters such as OAT1 [...] Read more.

High uric acid is associated with gout, hypertension, metabolic syndrome, cardiovascular disease, and kidney disease. URAT1 (SLC22A12), originally discovered in mice as Rst, is generally considered a very selective uric acid transporter compared to other closely-related kidney uric acid transporters such as OAT1 (SLC22A6, NKT) and OAT3 (SLC22A8). While the role of URAT1 in regulating human uric acid is well-established, in recent studies the gene has been linked to redox regulation in flies as well as progression of renal cell carcinoma. We have now identified over twenty metabolites in the Urat1 knockout that are generally distinct from metabolites accumulating in the Oat1 and Oat3 knockout mice, with distinct molecular properties as revealed by chemoinformatics and machine learning analysis. These metabolites are involved in seemingly disparate aspects of cellular metabolism, including pyrimidine, fatty acid, and amino acid metabolism. However, through integrative systems metabolic analysis of the transcriptomic and metabolomic data using a human metabolic reconstruction to build metabolic genome-scale models (GEMs), the cellular response to loss of Urat1/Rst revealed compensatory processes related to reactive oxygen species handling and maintaining redox state balances via Vitamin C metabolism and cofactor charging reactions. These observations are consistent with the increasingly appreciated role of the antioxidant properties of uric acid. Collectively, the results highlight the role of Urat1/Rst as a transporter strongly tied to maintaining redox homeostasis, with implications for metabolic side effects from drugs that block its function. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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12 pages, 3029 KiB

Open AccessArticle

Effects of Citrus kawachiensis Peel in Frailty-like Model Mice Induced by Low Protein Nutrition Disorders

by Toshiki Omasa, Satoshi Okuyama, Atsushi Sawamoto, Mitsunari Nakajima and Yoshiko Furukawa

Antioxidants 2023, 12(3), 779; https://doi.org/10.3390/antiox12030779 - 22 Mar 2023

Viewed by 1265

Abstract

“Frailty” caused by a decline in physiological reserve capacity, chronic inflammation, and oxidative stress in the elderly has recently become a major social issue. The present study examined the effects of the peel of Citrus kawachiensis (CK), which exhibits anti-inflammatory, antioxidant, and pro-neurogenesis [...] Read more.

“Frailty” caused by a decline in physiological reserve capacity, chronic inflammation, and oxidative stress in the elderly has recently become a major social issue. The present study examined the effects of the peel of Citrus kawachiensis (CK), which exhibits anti-inflammatory, antioxidant, and pro-neurogenesis activities in frailty-like model mice. Male C57BL/6 mice (15 weeks old) were fed an 18% protein diet (CON), a 2.5% protein diet (PM), and PM mixed with 1% dried CK peel powder for approximately 1 month. Mice were euthanized 2 or 8 days after a single intraperitoneal administration of lipopolysaccharide (LPS) and tissues were dissected. Among peripheral tissues, muscle weight, liver weight, and blood glucose levels were significantly higher in the PM–LPS–CK group than in the PM–LPS group. In the behavioral analysis, locomotive activity was significantly lower in the PM–LPS group than in the PM group. The reduction in locomotive activity in the PM–LPS–CK group was significantly smaller than that in the PM–LPS group. The quantification of microglia in the hippocampal stratum lacunosum-moleculare revealed that increases in the PM–LPS group were significantly suppressed by the dried CK peel powder. Furthermore, the quantification of synaptic vesicle membrane proteins in the hippocampal CA3 region showed down-regulated expression in the PM–LPS group, which was significantly ameliorated by the administration of the dried CK peel powder. Collectively, these results suggest that CK inhibits inflammation and oxidative stress induced by PM and LPS in the central nervous system and peripheral tissue. Therefore, C. kawachiensis is highly effective against “frailty”. Full article

(This article belongs to the Special Issue 10th Anniversary of Antioxidants-Advances in Health Outcomes of Oxidative Stress)

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20 pages, 4558 KiB

Open AccessReview

Activators of Nrf2 to Counteract Neurodegenerative Diseases

by Rosa Amoroso, Cristina Maccallini and Ilaria Bellezza

Antioxidants 2023, 12(3), 778; https://doi.org/10.3390/antiox12030778 - 22 Mar 2023

Cited by 9 | Viewed by 2145

Abstract

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and loss of nerve cells. Oxidative stress has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders since neuron cells are particularly vulnerable to [...] Read more.

Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and loss of nerve cells. Oxidative stress has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders since neuron cells are particularly vulnerable to oxidative damage. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is strictly related to anti-inflammatory and antioxidative cell response; therefore, its activation and the consequent enhancement of the related cellular pathways have been proposed as a potential therapeutic approach. Several Nrf2 activators with different mechanisms and diverse structures have been reported, but those applied for neurodisorders are still limited. However, in the very last few years, interesting progress has been made, particularly in enhancing the blood–brain barrier penetration, to make Nrf2 activators effective drugs, and in designing Nrf2-based multitarget-directed ligands to affect multiple pathways involved in the pathology of neurodegenerative diseases. The present review gives an overview of the most representative findings in this research area. Full article

(This article belongs to the Special Issue Molecular Targets of Oxidative Stress: Focus on the Nrf2 Signaling Pathway in Health and Disease)

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20 pages, 3876 KiB

Open AccessArticle

Nrf2 Activation Does Not Protect from Aldosterone-Induced Kidney Damage in Mice

by Ronja Brinks, Christoph Jan Wruck, Jutta Schmitz and Nicole Schupp

Antioxidants 2023, 12(3), 777; https://doi.org/10.3390/antiox12030777 - 22 Mar 2023

Cited by 2 | Viewed by 1578

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is downregulated in chronic kidney disease (CKD). Activation of Nrf2 might be a therapeutic option in CKD. Here we investigate the effect of Nrf2 activation on aldosterone (Aldo)-induced renal injury. Wild-type (WT) mice, transgenic Keap1 hypomorphic [...] Read more.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is downregulated in chronic kidney disease (CKD). Activation of Nrf2 might be a therapeutic option in CKD. Here we investigate the effect of Nrf2 activation on aldosterone (Aldo)-induced renal injury. Wild-type (WT) mice, transgenic Keap1 hypomorphic (Nrf2ꜛ, genotype results in upregulation of Nrf2 expression) mice and WT mice treated with the Nrf2 activator sulforaphane (Sulf) received Aldo for 4 weeks. In Aldo-treated mice, kidneys were significantly heavier and pathologically altered, reflected by increased urinary albumin levels and tissue damage. In Nrf2ꜛ-Aldo mice the tubule damage marker NGAL was significantly decreased. Increased oxidative damage markers (8-OHdG, 15-isoprostane F_2t) were measured in all Aldo-treated groups. Aldo-increased Nrf2 amounts were mainly found in the late tubule system. The amount of phosphorylated and thus putatively active Nrf2 was significantly increased by Aldo only in WT mice. However, expression of Nrf2 target genes NQO1 and HO1 was decreased in all Aldo-infused mice. GSK3β, which promotes Nrf2 degradation, was significantly increased in the kidneys of Aldo-treated WT mice. Neither genetic nor pharmacological Nrf2 activation was able to prevent oxidative injury induced by Aldo, probably due to induction of negative regulators of Nrf2. Full article

(This article belongs to the Special Issue Nrf2 in Kidney Injury and Physiology)

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14 pages, 1699 KiB

Open AccessCommunication

Assessment of Cystamine’s Radioprotective/Antioxidant Ability under High-Dose-Rate Irradiation: A Monte Carlo Multi-Track Chemistry Simulation Study

by Samafou Penabeï, Jintana Meesungnoen and Jean-Paul Jay-Gerin

Antioxidants 2023, 12(3), 776; https://doi.org/10.3390/antiox12030776 - 22 Mar 2023

Cited by 2 | Viewed by 1226

Abstract

(1) Background: cystamine and its reduced form cysteamine have radioprotective/antioxidant effects in vivo. In this study, we use an in vitro model system to examine the behavior of cystamine towards the reactive primary species produced during the radiolysis of the Fricke dosimeter under [...] Read more.

(1) Background: cystamine and its reduced form cysteamine have radioprotective/antioxidant effects in vivo. In this study, we use an in vitro model system to examine the behavior of cystamine towards the reactive primary species produced during the radiolysis of the Fricke dosimeter under high dose-rate irradiation conditions. (2) Methods: our approach was to use the familiar radiolytic oxidation of ferrous to ferric ions as an indicator of the radioprotective/antioxidant capacity of cystamine. A Monte Carlo computer code was used to simulate the multi-track radiation-induced chemistry of aerated and deaerated Fricke-cystamine solutions as a function of dose rate while covering a large range of cystamine concentrations. (3) Results: our simulations revealed that cystamine provides better protection at pulsed dose rates compared to conventional, low-dose-rate irradiations. Furthermore, our simulations confirmed the radical-capturing ability of cystamine, clearly indicating the strong antioxidant profile of this compound. (4) Conclusion: assuming that these findings can be transposable to cells and tissues at physiological pH, it is suggested that combining cystamine with FLASH-RT could be a promising approach to further enhance the therapeutic ratio of cancer cure. Full article

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16 pages, 1715 KiB

Open AccessArticle

Advanced Processing of Giant Kelp (Macrocystis pyrifera) for Protein Extraction and Generation of Hydrolysates with Anti-Hypertensive and Antioxidant Activities In Vitro and the Thermal/Ionic Stability of These Compounds

by Paniz Biparva, Armin Mirzapour-Kouhdasht, Shahriyar Valizadeh and Marco Garcia-Vaquero

Antioxidants 2023, 12(3), 775; https://doi.org/10.3390/antiox12030775 - 22 Mar 2023

Cited by 2 | Viewed by 2505

Abstract

In this study, giant kelp was explored under various conventional and ultrasound-assisted extraction (UAE) conditions for the extraction of protein, its hydrolysis, and ultrafiltration to generate multiple fractions. The amino acid composition of all the fractions and their biological activities in vitro, including [...] Read more.

In this study, giant kelp was explored under various conventional and ultrasound-assisted extraction (UAE) conditions for the extraction of protein, its hydrolysis, and ultrafiltration to generate multiple fractions. The amino acid composition of all the fractions and their biological activities in vitro, including angiotensin-converting enzyme I (ACE) inhibitory activity and antioxidant activities (2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, reducing power (RP), and ferrous chelating (FC) activities) were tested by storing the compounds for 2 weeks at various temperatures (−20–60 °C) and pHs (2–11) to elucidate their thermal and ionic stability, respectively. The yield of protein extraction using the conventional method was lower (≈39%) compared to the use of UAE (150 W, 15 min), which achieved protein recoveries of approximately 60%. After enzymatic hydrolysis and ultrafiltration, low-molecular-weight (MW) hydrolysates had the highest levels of ACE inhibitory (80%), DPPH (84%), RP (0.71 mM trolox equivalents), and FC (81%) activities. Amino acids associated with peptides of high biological activities, such as Val, Ala, Asx, Gly, Lys, Met, Leu, and His, were at higher levels in the low MW fraction compared to any other sample. The biological activities in vitro of all the samples fluctuated under the multiple storage conditions studied, with the highest stability of all the samples appreciated at −20 °C and pH 7. This study shows for the first time the use of giant kelp as a promising source of bioactive peptides and indicates the optimum processing and storing conditions for the use of these compounds as nutraceuticals or functional foods that could help in the prevention of cardiovascular disorders and multiple chronic diseases associated with oxidative damage. Full article

(This article belongs to the Special Issue Antioxidant Properties and Potential Mechanisms of Protein Hydrolysates)

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14 pages, 1568 KiB

Open AccessArticle

Hangover-Relieving Effect of Ginseng Berry Kombucha Fermented by Saccharomyces cerevisiae and Gluconobacter oxydans in Ethanol-Treated Cells and Mice Model

by Eun Jung Choi, Hyeongyeong Kim, Ki-Bae Hong, Hyung Joo Suh and Yejin Ahn

Antioxidants 2023, 12(3), 774; https://doi.org/10.3390/antiox12030774 - 22 Mar 2023

Cited by 8 | Viewed by 2147

Abstract

This study aimed to evaluate the hangover relieving effect of ginseng berry kombucha (GBK) fermented with Saccharomyces cerevisiae and Gluconobacter oxydans in in vitro and in vivo models. The antioxidant activity and oxidative stress inhibitory effect of GBK were evaluated in ethanol-treated human [...] Read more.

This study aimed to evaluate the hangover relieving effect of ginseng berry kombucha (GBK) fermented with Saccharomyces cerevisiae and Gluconobacter oxydans in in vitro and in vivo models. The antioxidant activity and oxidative stress inhibitory effect of GBK were evaluated in ethanol-treated human liver HepG2 cells. In addition, biochemical and behavioral analyses of ethanol treated male ICR mice were performed to confirm the anti-hangover effect of GBK. The radical scavenging activity of GBK was increased by fermentation, and the total ginsenoside content of GBK was 70.24 μg/mL. In HepG2 cells, in which oxidative stress was induced using ethanol, GBK significantly increased the expression of antioxidant enzymes by upregulating the Nrf2/Keap1 pathway. Moreover, GBK (15 and 30 mg/kg) significantly reduced blood ethanol and acetaldehyde concentrations in ethanol-treated mice. GBK significantly increased the levels of alcohol-metabolizing enzymes, including alcohol dehydrogenase and acetaldehyde dehydrogenase. The balance beam test and elevated plus maze test revealed that high-dose GBK significantly ameliorated ethanol-induced behavioral changes. Collectively, GBK exerted a protective effect against ethanol-induced liver damage by regulating the Nrf2/Keap1 pathway. Full article

(This article belongs to the Special Issue Oxidative Stress in Hepatic Injury)

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11 pages, 993 KiB

Open AccessHypothesis

The Combined Treatment of Glutathione Sodium Salt and Ascorbic Acid for Preventing Contrast-Associated Acute Kidney Injury in ST-Elevation Myocardial Infarction Patients Undergoing Primary PCI: A Hypothesis to Be Validated

by Alessio Arrivi, Giovanni Truscelli, Giacomo Pucci, Francesco Barillà, Roberto Carnevale, Cristina Nocella, Martina Sordi, Marcello Dominici, Gaetano Tanzilli and Enrico Mangieri

Antioxidants 2023, 12(3), 773; https://doi.org/10.3390/antiox12030773 - 22 Mar 2023

Cited by 3 | Viewed by 1452

Abstract

The occurrence of Contrast-Associated Acute Kidney Injury (CA-AKI) in patients with ST-Elevation Myocardial Infarction (STEMI) has a negative impact on the length of hospital stay and mortality. Reactive Oxygen Species (ROS) release, along with vasoconstriction and hypoperfusion, play a key role in its [...] Read more.

The occurrence of Contrast-Associated Acute Kidney Injury (CA-AKI) in patients with ST-Elevation Myocardial Infarction (STEMI) has a negative impact on the length of hospital stay and mortality. Reactive Oxygen Species (ROS) release, along with vasoconstriction and hypoperfusion, play a key role in its development. To date, there is still no validated prophylactic therapy for this disease. The use of antioxidants, based on experimental and clinical studies, looks promising. Taking into consideration previous literature, we speculate that an early, combined and prolonged intravenous administration of both Glutathione (GSH) and ascorbic acid in STEMI patients undergoing primary Percutaneous Coronary Intervention (pPCI) may be of value in counteracting the occurrence of CA-AKI. We aimed at evaluating this hypothesis by applying a multicenter research protocol, using a double-blind randomized, placebo-controlled trial design. The primary endpoint will be to test the efficacy of this combined antioxidant therapy in reducing the occurrence of renal damage, in patients with acute myocardial infarction treated with pPCI. Furthermore, we will investigate the effect of the study compounds on changes in oxidative stress markers and platelet activation levels through bio-humoral analyses. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiorenal System)

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17 pages, 823 KiB

Open AccessArticle

Dietary Guanidine Acetic Acid Improves Ruminal Antioxidant Capacity and Alters Rumen Fermentation and Microflora in Rapid-Growing Lambs

by Wenjuan Li, Zhaoyang Cui, Yaowen Jiang, Ailiyasi Aisikaer, Qichao Wu, Fang Zhang, Weikang Wang, Yukun Bo and Hongjian Yang

Antioxidants 2023, 12(3), 772; https://doi.org/10.3390/antiox12030772 - 22 Mar 2023

Cited by 3 | Viewed by 1782

Abstract

Guanidine acetic acid (GAA) has been reported to improve growth performance, nutrient utilization, and meat quality in livestock. This study aimed to investigate whether coated GAA (CGAA) in comparison with uncoated GAA (UGAA) could have different effects on rumen fermentation, antioxidant capacity, and [...] Read more.

Guanidine acetic acid (GAA) has been reported to improve growth performance, nutrient utilization, and meat quality in livestock. This study aimed to investigate whether coated GAA (CGAA) in comparison with uncoated GAA (UGAA) could have different effects on rumen fermentation, antioxidant capacity, and microflora composition in the rumen. Seventy-two lambs were randomly arranged in a 2 × 3 factorial experiment design with two diets of different forage type (OH: oaten hay; OHWS: oaten hay plus wheat silage) and three GAA treatments within each diet (control, diet without GAA addition; UGAA, uncoated GAA; CGAA, coated GAA). The whole feeding trial lasted for 120 days. The lambs in the OH group presented lower total volatile fatty acid (VFA), alpha diversity, Firmicutes, NK4A214_group, and Lachnospiraceae_NK3A20_group than those on the OHWS diet in the last 60 days of the feeding stage (p < 0.05). Regardless of what GAA form was added, dietary GAA supplementation increased the total VFA, microbial crude protein (MCP), adenosine triphosphate (ATP), and antioxidant capacity in rumen during lamb feedlotting (p < 0.05). However, molar propionate proportion, acetate:propionate ratio (A:P), and relative Succiniclasticum abundance decreased with GAA addition in the first 60 days of the growing stage, while the molar butyrate proportion and NK4A214_group (p < 0.05) in response to GAA addition increased in the last 60 days of feeding. These findings indicated that dietary GAA enhanced antioxidant capacity and fermentation characteristics in the rumen, but the addition of uncoated GAA in diets might cause some dysbacteriosis of the rumen microbiota. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Animal Nutrition)

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28 pages, 2192 KiB

Open AccessReview

Nutriepigenomics in Environmental-Associated Oxidative Stress

by Karla Rubio, Estefani Y. Hernández-Cruz, Diana G. Rogel-Ayala, Pouya Sarvari, Ciro Isidoro, Guillermo Barreto and José Pedraza-Chaverri

Antioxidants 2023, 12(3), 771; https://doi.org/10.3390/antiox12030771 - 21 Mar 2023

Cited by 4 | Viewed by 2516

Abstract

Complex molecular mechanisms define our responses to environmental stimuli. Beyond the DNA sequence itself, epigenetic machinery orchestrates changes in gene expression induced by diet, physical activity, stress and pollution, among others. Importantly, nutrition has a strong impact on epigenetic players and, consequently, sustains [...] Read more.

Complex molecular mechanisms define our responses to environmental stimuli. Beyond the DNA sequence itself, epigenetic machinery orchestrates changes in gene expression induced by diet, physical activity, stress and pollution, among others. Importantly, nutrition has a strong impact on epigenetic players and, consequently, sustains a promising role in the regulation of cellular responses such as oxidative stress. As oxidative stress is a natural physiological process where the presence of reactive oxygen-derived species and nitrogen-derived species overcomes the uptake strategy of antioxidant defenses, it plays an essential role in epigenetic changes induced by environmental pollutants and culminates in signaling the disruption of redox control. In this review, we present an update on epigenetic mechanisms induced by environmental factors that lead to oxidative stress and potentially to pathogenesis and disease progression in humans. In addition, we introduce the microenvironment factors (physical contacts, nutrients, extracellular vesicle-mediated communication) that influence the epigenetic regulation of cellular responses. Understanding the mechanisms by which nutrients influence the epigenome, and thus global transcription, is crucial for future early diagnostic and therapeutic efforts in the field of environmental medicine. Full article

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16 pages, 2951 KiB

Open AccessArticle

The NADPH Oxidase Inhibitors Apocynin and Diphenyleneiodonium Protect Rats from LPS-Induced Pulmonary Inflammation

by Ahmed Kouki, Wafa Ferjani, Néziha Ghanem-Boughanmi, Mossadok Ben-Attia, Pham My-Chan Dang, Abdelaziz Souli and Jamel El-Benna

Antioxidants 2023, 12(3), 770; https://doi.org/10.3390/antiox12030770 - 21 Mar 2023

Cited by 4 | Viewed by 2000

Abstract

Inflammation is the body’s response to insults, for instance, lung inflammation is generally caused by pathogens or by exposure to pollutants, irritants and toxins. This process involves many inflammatory cells such as epithelial cells, monocytes, macrophages and neutrophils. These cells produce and release [...] Read more.

Inflammation is the body’s response to insults, for instance, lung inflammation is generally caused by pathogens or by exposure to pollutants, irritants and toxins. This process involves many inflammatory cells such as epithelial cells, monocytes, macrophages and neutrophils. These cells produce and release inflammatory mediators such as pro-inflammatory cytokines, lipids and reactive oxygen species (ROS). Lung epithelial cells and phagocytes (monocytes, macrophages and neutrophils) produce ROS mainly by the NADPH oxidase NOX1 and NOX2, respectively. The aim of this study was to investigate the effects of two NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI), on lipopolysaccharide (LPS)-induced lung inflammation in rats. Our results showed that apocynin and DPI attenuated the LPS-induced morphological and histological alterations of the lung, reduced edema and decreased lung permeability. The evaluation of oxidative stress markers in lung homogenates showed that apocynin and DPI inhibited LPS-induced NADPH oxidase activity, and restored superoxide dismutase (SOD) and catalase activity in the lung resulting in the reduction in LPS-induced protein and lipid oxidation. Additionally, apocynin and DPI decreased LPS-induced MPO activity in bronchoalveolar liquid and lung homogenates, TNF-α and IL-1β in rat plasma. NADPH oxidase inhibition could be a new therapeutic strategy for the treatment of inflammatory lung diseases. Full article

(This article belongs to the Special Issue NADPH Oxidases: Physiology and Therapeutic Potential)

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19 pages, 2173 KiB

Open AccessReview

Recent Perspective of Lactobacillus in Reducing Oxidative Stress to Prevent Disease

by Tingting Zhao, Haoran Wang, Zhenjiang Liu, Yang Liu, DeJi, Bin Li and Xiaodan Huang

Antioxidants 2023, 12(3), 769; https://doi.org/10.3390/antiox12030769 - 21 Mar 2023

Cited by 8 | Viewed by 2762

Abstract

During oxidative stress, an important factor in the development of many diseases, cellular oxidative and antioxidant activities are imbalanced due to various internal and external factors such as inflammation or diet. The administration of probiotic Lactobacillus strains has been shown to confer a [...] Read more.

During oxidative stress, an important factor in the development of many diseases, cellular oxidative and antioxidant activities are imbalanced due to various internal and external factors such as inflammation or diet. The administration of probiotic Lactobacillus strains has been shown to confer a range of antibacterial, anti-inflammatory, antioxidant, and immunomodulatory effects in the host. This review focuses on the potential role of oxidative stress in inflammatory bowel diseases (IBD), cancer, and liver-related diseases in the context of preventive and therapeutic effects associated with Lactobacillus. This article reviews studies in cell lines and animal models as well as some clinical population reports that suggest that Lactobacillus could alleviate basic symptoms and related abnormal indicators of IBD, cancers, and liver damage, and covers evidence supporting a role for the Nrf2, NF-κB, and MAPK signaling pathways in the effects of Lactobacillus in alleviating inflammation, oxidative stress, aberrant cell proliferation, and apoptosis. This review also discusses the unmet needs and future directions in probiotic Lactobacillus research including more extensive mechanistic analyses and more clinical trials for Lactobacillus-based treatments. Full article

(This article belongs to the Special Issue Antioxidant Activity of Fermented Foods and Food Microorganisms)

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18 pages, 3471 KiB

Open AccessArticle

Taurine as Antioxidant in a Novel Cell- and Oxygen Carrier-Free Perfusate for Normothermic Machine Perfusion of Porcine Kidneys

by Laura Zarnitz, Benedict M. Doorschodt, Lisa Ernst, Aisa Hosseinnejad, Eileen Edgworth, Tamara Fechter, Alexander Theißen, Sonja Djudjaj, Peter Boor, Rolf Rossaint, René H. Tolba and Christian Bleilevens

Antioxidants 2023, 12(3), 768; https://doi.org/10.3390/antiox12030768 - 21 Mar 2023

Cited by 1 | Viewed by 1719

Abstract

Donor organ-shortage has resulted in the increased use of marginal grafts; however, normothermic machine perfusion (NMP) holds the potential for organ viability assessment and restoration of marginal grafts prior to transplantation. Additionally, cell-, oxygen carrier-free and antioxidants-supplemented solutions could potentially prevent adverse effects [...] Read more.

Donor organ-shortage has resulted in the increased use of marginal grafts; however, normothermic machine perfusion (NMP) holds the potential for organ viability assessment and restoration of marginal grafts prior to transplantation. Additionally, cell-, oxygen carrier-free and antioxidants-supplemented solutions could potentially prevent adverse effects (transfusion reactions, inflammation, hemolysis), associated with the use of autologous packed red blood cell (pRBC)-based perfusates. This study compared 6 h NMP of porcine kidneys, using an established pRBC-based perfusate (pRBC, n = 7), with the novel cell- and oxygen carrier-free organ preservation solution Ecosol, containing taurine (Ecosol, n = 7). Despite the enhanced tissue edema and tubular injury in the Ecosol group, related to a suboptimal molecular mass of polyethylene glycol as colloid present in the solution, functional parameters (renal blood flow, intrarenal resistance, urinary flow, pH) and oxygenation (arterial pO₂, absence of hypoxia-inducible factor 1-alpha) were similar to the pRBC group. Furthermore, taurine significantly improved the antioxidant capacity in the Ecosol group, reflected in decreased lactate dehydrogenase, urine protein and tubular vacuolization compared to pRBC. This study demonstrates the feasibility of 6 h NMP using a taurine containing, cell- and oxygen carrier-free perfusate, achieving a comparable organ quality to pRBC perfused porcine kidneys. Full article

(This article belongs to the Special Issue Antioxidants and Their Role in Kidney Machine Perfusion and Kidney Injury)

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20 pages, 2535 KiB

Open AccessReview

Recent Advances in Biotechnologies for the Treatment of Environmental Pollutants Based on Reactive Sulfur Species

by Kaili Fan, Wei Wang, Xijun Xu, Yuan Yuan, Nanqi Ren, Duu-Jong Lee and Chuan Chen

Antioxidants 2023, 12(3), 767; https://doi.org/10.3390/antiox12030767 - 21 Mar 2023

Cited by 4 | Viewed by 2105

Abstract

The definition of reactive sulfur species (RSS) is inspired by the reactivity and variable chemical valence of sulfur. Sulfur is an essential element for life and is a part of global geochemical cycles. Wastewater treatment bioreactors can be divided into two major categories: [...] Read more.

The definition of reactive sulfur species (RSS) is inspired by the reactivity and variable chemical valence of sulfur. Sulfur is an essential element for life and is a part of global geochemical cycles. Wastewater treatment bioreactors can be divided into two major categories: sulfur reduction and sulfur oxidation. We review the origins of the definition of RSS and related biotechnological processes in environmental management. Sulfate reduction, sulfide oxidation, and sulfur-based redox reactions are key to driving the coupled global carbon, nitrogen, and sulfur co-cycles. This shows the coupling of the sulfur cycle with the carbon and nitrogen cycles and provides insights into the global material−chemical cycle. We also review the biological classification and RSS metabolic mechanisms of functional microorganisms involved in the biological processes, such as sulfate-reducing and sulfur-oxidizing bacteria. Developments in molecular biology and genomic technologies have allowed us to obtain detailed information on these bacteria. The importance of RSS in environmental technologies requires further consideration. Full article

(This article belongs to the Special Issue Reactive Sulfur Species in Microorganisms)

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18 pages, 1960 KiB

Open AccessArticle

Photobiomodulation Controls Keratinocytes Inflammatory Response through Nrf2 and Reduces Langerhans Cells Activation

by Sara Salman, Cyprien Guermonprez, Laurent Peno-Mazzarino, Elian Lati, Audrey Rousseaud, Lieve Declercq and Saadia Kerdine-Römer

Antioxidants 2023, 12(3), 766; https://doi.org/10.3390/antiox12030766 - 21 Mar 2023

Cited by 5 | Viewed by 3143

Abstract

Photobiomodulation (PBM) is rapidly gaining traction as a valuable tool in dermatology for treating many inflammatory skin conditions using low levels of visible light or near-infrared radiation. However, the physiological regulatory pathways responsible for the anti-inflammatory effect of PBM have not been well [...] Read more.

Photobiomodulation (PBM) is rapidly gaining traction as a valuable tool in dermatology for treating many inflammatory skin conditions using low levels of visible light or near-infrared radiation. However, the physiological regulatory pathways responsible for the anti-inflammatory effect of PBM have not been well defined. Since previous studies showed that nuclear factor-erythroid 2 like 2 (Nrf2) is a master regulator of the skin inflammatory response, we have addressed its role in controlling inflammation by PBM. Primary human keratinocytes (KCs) stimulated with 2,4-dinitrochlorobenzene (DNCB) to mimic pro-inflammatory stress were illuminated with two wavelengths: 660 nm or 520 nm. Both lights significantly reduced the mRNA expression of the DNCB-triggered TNF-α, IL-6, and IL-8 cytokines in KCs, while they enhanced Nrf2 pathway activation. PBM-induced Nrf2 is a key regulator of the inflammatory response in KCs since its absence abolished the regulatory effect of light on cytokines production. Further investigations of the mechanisms contributing to the immunoregulatory effect of PBM in inflamed human skin explants showed that 660 nm light prevented Langerhans cells migration into the dermis, preserving their dendricity, and decreased pro-inflammatory cytokine production compared to the DNCB-treated group. This study is the first to report that the PBM-mediated anti-inflammatory response in KCs is Nrf2-dependent and further support the role of PBM in skin immunomodulation. Therefore, PBM should be considered a promising alternative or complementary therapeutic approach for treating skin-related inflammatory diseases. Full article

(This article belongs to the Special Issue Redox Regulation in Inflammation and Disease – 2nd Edition)

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20 pages, 4710 KiB

Open AccessArticle

Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration

by Lena M. Ernst, Laura Mondragón, Joana Ramis, Muriel F. Gustà, Tetyana Yudina, Eudald Casals, Neus G. Bastús, Guillermo Fernández-Varo, Gregori Casals, Wladimiro Jiménez and Victor Puntes

Antioxidants 2023, 12(3), 765; https://doi.org/10.3390/antiox12030765 - 21 Mar 2023

Cited by 6 | Viewed by 1699

Abstract

Nanoparticle (NP) pharmacokinetics significantly differ from traditional small molecule principles. From this emerges the need to create new tools and concepts to harness their full potential and avoid unnecessary risks. Nanoparticle pharmacokinetics strongly depend on size, shape, surface functionalisation, and aggregation state, influencing [...] Read more.

Nanoparticle (NP) pharmacokinetics significantly differ from traditional small molecule principles. From this emerges the need to create new tools and concepts to harness their full potential and avoid unnecessary risks. Nanoparticle pharmacokinetics strongly depend on size, shape, surface functionalisation, and aggregation state, influencing their biodistribution, accumulation, transformations, and excretion profile, and hence their efficacy and safety. Today, while NP biodistribution and nanoceria biodistribution have been studied often at short times, their long-term accumulation and excretion have rarely been studied. In this work, 3 nm nanoceria at 5.7 mg/kg of body weight was intravenously administrated in a single dose to healthy mice. Biodistribution was measured in the liver, spleen, kidney, lung, brain, lymph nodes, ovary, bone marrow, urine, and faeces at different time points (1, 9, 30, and 100 days). Biodistribution and urinary and faecal excretion were also studied in rats placed in metabolic cages at shorter times. The similarity of results of different NPs in different models is shown as the heterogeneous nanoceria distribution in organs. After the expectable accumulation in the liver and spleen, the concentration of cerium decays exponentially, accounting for about a 50% excretion of cerium from the body in 100 days. Cerium ions, coming from NP dissolution, are most likely excreted via the urinary tract, and ceria nanoparticles accumulated in the liver are most likely excreted via the hepatobiliary route. In addition, nanoceria looks safe and does not damage the target organs. No weight loss or apathy was observed during the course of the experiments. Full article

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16 pages, 4394 KiB

Open AccessArticle

Antrodin C Isolated from Antrodia Cinnamomea Induced Apoptosis through ROS/AKT/ERK/P38 Signaling Pathway and Epigenetic Histone Acetylation of TNFα in Colorectal Cancer Cells

by Yung-Yu Hsieh, Ko-Chao Lee, Kung-Chuan Cheng, Kam-Fai Lee, Ya-Ling Yang, Hsin-Tung Chu, Ting-Wei Lin, Chin-Chu Chen, Meng-Chiao Hsieh, Cheng-Yi Huang, Hsing-Chun Kuo and Chih-Chuan Teng

Antioxidants 2023, 12(3), 764; https://doi.org/10.3390/antiox12030764 - 21 Mar 2023

Cited by 1 | Viewed by 2139

Abstract

Background: Antrodin C, a maleimide derivative compound isolated from the ethanol extract of the mycelium of Antrodia cinnamomea, is an endemic fungus of Taiwan and a potential chemoprotective agent. However, the molecular mechanisms underlying the mode of action of antrodin C on [...] Read more.

Background: Antrodin C, a maleimide derivative compound isolated from the ethanol extract of the mycelium of Antrodia cinnamomea, is an endemic fungus of Taiwan and a potential chemoprotective agent. However, the molecular mechanisms underlying the mode of action of antrodin C on cancer cells, especially in human colorectal cancer (CRC), remain unclear. Methods: The cell death and ROS of the antrodin-C-treated HCT-116 cells were measured by annexin V–FITC/propidium iodide staining, DCFDA, and Fluo-3 fluorescence staining assays. Moreover, signaling molecules regulating TNFα cell death pathways and ROS/AKT/ERK/P38 pathways were also detected in cells treated with antrodin C by Western blotting and chromatin immunoprecipitation. The effects of antrodin C were determined in HCT-116 cell xenograft animal models in terms of tumor volumes and histopathological evaluation. Results: Treatment with antrodin C triggered the activation of extrinsic apoptosis pathways (TNFα, Bax, caspase-3, and -9), and also suppressed the expression of anti-apoptotic molecules Bcl-2 in HCT-116 cells in a time-dependent manner. Antrodin C also decreased cell proliferation and growth through the inactivation of cyclin D1/cyclin for the arrest of the cell cycle at the G1 phase. The activation of the ROS/AKT/ERK/P38 pathways was involved in antrodin-C-induced transcriptional activation, which implicates the role of the histone H3K9K14ac (Acetyl Lys9/Lys14) of the TNFα promoters. Immunohistochemical analyses revealed that antrodin C treatment significantly induced TNFα levels, whereas it decreased the levels of PCNA, cyclin D1, cyclin E, and MMP-9 in an in vivo xenograft mouse model. Thus, antrodin C induces cell apoptosis via the activation of the ROS/AKT/ERK/P38 signaling modules, indicating a new mechanism for antrodin C to treat CRC in vitro and in vivo. Full article

(This article belongs to the Special Issue Natural Products as Agents of Targeted Cancer Therapeutic Action)

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11 pages, 2042 KiB

Open AccessArticle

Host–Guest Complexes HP-β-CD/Citrus Antioxidants: Exploratory Evaluations of Enhanced Properties in Biodegradable Film Packaging

by Giovanni Gallo, Domenico Zannini, Barbara Immirzi, Alessandra De Bruno, Gabriella Fiorentino and Giovanni Dal Poggetto

Antioxidants 2023, 12(3), 763; https://doi.org/10.3390/antiox12030763 - 21 Mar 2023

Cited by 1 | Viewed by 1605

Abstract

The aim of this work was to exploit the antioxidant potential of molecules recovered during the pectin purification process of citrus lemon waste and to encapsulate them in stable pectin films, with a view to a green and circular economy process. Antioxidant molecules [...] Read more.

The aim of this work was to exploit the antioxidant potential of molecules recovered during the pectin purification process of citrus lemon waste and to encapsulate them in stable pectin films, with a view to a green and circular economy process. Antioxidant molecules were recovered during the pectin purification process, further recovering matter from the waste. Seven molecules were identified and quantified, and the antioxidant power of the mixture and its stability over time was evaluated. To improve the stability of the bioactive fraction, this was complexed with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD); indeed, this procedure increased their thermal stability from 120 °C up to 250 °C, as verified by thermogravimetry. Furthermore, the most promising complexes were studied under autoclave-like conditions (120 °C, 28 min) to simulate thermal sterilization. The antioxidants and HP-β-CD were combined in a pectin film, showing increased stability over time (up to three times) compared to uncomplexed antioxidants. This process represents a first step towards the development of applicable devices for the delivery of antioxidant molecules. Full article

(This article belongs to the Special Issue Applications and Health Benefits of Novel Antioxidant Biomaterials)

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11 pages, 1818 KiB

Open AccessArticle

Evaluation of the Physical and Oxidative Stabilities of Fish Oil-in-Water-in-Olive Oil Double Emulsions (O₁/W/O₂) Stabilized with Whey Protein Hydrolysate

by Marta Padial-Domínguez, Pedro J. García-Moreno, Rubén González-Beneded, Antonio Guadix and Emilia M. Guadix

Antioxidants 2023, 12(3), 762; https://doi.org/10.3390/antiox12030762 - 21 Mar 2023

Cited by 1 | Viewed by 1588

Abstract

This work studied the physical and oxidative stabilities of fish oil-in-water-in-olive oil double emulsions (O₁/W/O₂), where whey protein hydrolysate was used as a hydrophilic emulsifier. A 20 wt.% fish oil-in-water emulsion, stabilized with whey protein hydrolysate (oil: protein ratio [...] Read more.

This work studied the physical and oxidative stabilities of fish oil-in-water-in-olive oil double emulsions (O₁/W/O₂), where whey protein hydrolysate was used as a hydrophilic emulsifier. A 20 wt.% fish oil-in-water emulsion, stabilized with whey protein hydrolysate (oil: protein ratio of 5:2 w/w) and with a zeta potential of ~−40 mV, only slightly increased its D_4,3 value during storage at 8 °C for seven days (from 0.725 to 0.897 µm), although it showed severe physical destabilization when stored at 25 °C for seven days (D_4,3 value increased from 0.706 to 9.035 µm). The oxidative stability of the 20 wt.% fish oil-in-water emulsion decreased when the storage temperature increased (25 vs. 8 °C) as indicated by peroxide and p-anisidine values, both in the presence or not of prooxidants (Fe²⁺). Confocal microscopy images confirmed the formation of 20 wt.% fish oil-in-water-in-olive oil (ratio 25:75 w/w) using Polyglycerol polyricinoleate (PGPR, 4 wt.%). Double emulsions were fairly physically stable for 7 days (both at 25 and 8 °C) (Turbiscan stability index, TSI < 4). Moreover, double emulsions had low peroxide (<7 meq O₂/kg oil) and p-anisidine (<7) values that did not increase during storage independently of the storage temperature (8 or 25 °C) and the presence or not of prooxidants (Fe²⁺), which denotes oxidative stability. Full article

(This article belongs to the Special Issue Advances in Controlling Lipid Peroxidation in Bulk and in Emulsified Oils)

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15 pages, 926 KiB

Open AccessArticle

Antioxidant Characterization of Six Tomato Cultivars and Derived Products Destined for Human Consumption

by Anna Rita Bianchi, Ermenegilda Vitale, Valeria Guerretti, Giancarlo Palumbo, Isabella Maria De Clemente, Luca Vitale, Carmen Arena and Anna De Maio

Antioxidants 2023, 12(3), 761; https://doi.org/10.3390/antiox12030761 - 21 Mar 2023

Cited by 5 | Viewed by 2856

Abstract

The consumption of fresh tomatoes and processed tomato products is widespread in the Mediterranean diet. This fruit is a valuable source of antioxidants and plays an important role in preventing oxidative stress. This study aimed to investigate the content of antioxidants and measure [...] Read more.

The consumption of fresh tomatoes and processed tomato products is widespread in the Mediterranean diet. This fruit is a valuable source of antioxidants and plays an important role in preventing oxidative stress. This study aimed to investigate the content of antioxidants and measure the total antioxidant capacity (ABTS and DPPH assays) in the peel, pulp, and seed fractions of six tomato cultivars. Finally, some bioactive compounds and total antioxidant activity were also determined in homemade tomato purees, since such homemade production is commonplace in Southern Italy. The level of antioxidants and total antioxidant capacity in each fraction were also calculated based on their actual fresh weight in the whole tomato. The overall results indicated that the peel and seeds of all analysed tomato cultivars contribute significantly to the antioxidant charge of the fruits. Consequently, consuming tomatoes without peel and seeds results in a substantial loss of compounds beneficial for human health. Our results also showed that phenolic and lycopene content, as well as antioxidant activities in all purees are higher than in fresh tomatoes. Based on this evidence, producing homemade tomato puree is a good practice, and its consumption helps prevent oxidative stress damage. Full article

(This article belongs to the Special Issue Valorization of the Antioxidant Power of Nature Compounds)

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18 pages, 2103 KiB

Open AccessArticle

Impact of Bariatric Surgery on the Stability of the Genetic Material, Oxidation, and Repair of DNA and Telomere Lengths

by Franziska Ferk, Miroslav Mišík, Benjamin Ernst, Gerhard Prager, Christoph Bichler, Doris Mejri, Christopher Gerner, Andrea Bileck, Michael Kundi, Sabine Langie, Klaus Holzmann and Siegfried Knasmueller

Antioxidants 2023, 12(3), 760; https://doi.org/10.3390/antiox12030760 - 21 Mar 2023

Cited by 1 | Viewed by 1681

Abstract

Obesity causes genetic instability, which plays a key-role in the etiology of cancer and aging. We investigated the impact of bariatric surgery (BS) on DNA repair, oxidative DNA damage, telomere lengths, alterations of antioxidant enzymes and, selected proteins which reflect inflammation. The study [...] Read more.

Obesity causes genetic instability, which plays a key-role in the etiology of cancer and aging. We investigated the impact of bariatric surgery (BS) on DNA repair, oxidative DNA damage, telomere lengths, alterations of antioxidant enzymes and, selected proteins which reflect inflammation. The study was realized with BS patients (n = 35). DNA damage, base oxidation, BER, and NER were measured before and 1 month and 6 months after surgery with the single-cell gel electrophoresis technique. SOD and GPx were quantified spectrophotometrically, malondealdehyde (MDA) was quantified by HPLC. Telomere lengths were determined with qPCR, and plasma proteome profiling was performed with high-resolution mass spectrophotometry. Six months after the operations, reduction of body weight by 27.5% was observed. DNA damage decreased after this period, this effect was paralleled by reduced formation of oxidized DNA bases, a decline in the MDA levels and of BER and NER, and an increase in the telomere lengths. The activities of antioxidant enzymes were not altered. Clear downregulation of certain proteins (CRP, SAA1) which reflect inflammation and cancer risks was observed. Our findings show that BS causes reduced oxidative damage of DNA bases, possibly as a consequence of reduction of inflammation and lipid peroxidation, and indicate that the surgery has beneficial long-term health effects. Full article

(This article belongs to the Special Issue Oxidative Stress in Obesity-II)

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13 pages, 1378 KiB

Open AccessArticle

Increased SIRT1 Concentration Following Four Years of Selenium and Q₁₀ Intervention Associated with Reduced Cardiovascular Mortality at 10-Year Follow-Up—Sub-Study of a Previous Prospective Double-Blind Placebo-Controlled Randomized Clinical Trial

by Trine Baur Opstad, Jan Alexander, Jan Aaseth, Anders Larsson, Ingebjørg Seljeflot and Urban Alehagen

Antioxidants 2023, 12(3), 759; https://doi.org/10.3390/antiox12030759 - 21 Mar 2023

Cited by 4 | Viewed by 3752

Abstract

Background: Selenium and coenzyme Q₁₀ (SeQ₁₀) possess antioxidant and anti-inflammatory properties, potentially mediated via Sirtuin1 (SIRT1). We aimed to investigate the influence of a SeQ₁₀ intervention on SIRT1 concentration, with potential interactions with microRNAs. Methods: In this [...] Read more.

Background: Selenium and coenzyme Q₁₀ (SeQ₁₀) possess antioxidant and anti-inflammatory properties, potentially mediated via Sirtuin1 (SIRT1). We aimed to investigate the influence of a SeQ₁₀ intervention on SIRT1 concentration, with potential interactions with microRNAs. Methods: In this sub-study of a prospective double-blind placebo-controlled clinical trial, healthy subjects (mean age 76 years) were randomized to receive an active treatment (n = 165, combined 200 µg/day of Se and 200 mg/day of Q₁₀) or a placebo (n = 161). SIRT1 concentration and microRNAs were measured with ELISA and PCR, respectively. Results: After four years, SIRT1 concentration was increased in the active treatment group, with mean (SD) ng/mL of 469 (436) vs. 252 (162), p < 0.001, and decreased in the placebo group, 190 (186) vs. 269 (172), p = 0.002, and the differences between the groups were significant (p = 0.006, adjusted). Those who suffered CV death during a 10-year follow-up (n = 25 and n = 52 in the active treatment and placebo groups, respectively) had significantly lower baseline SIRT1 concentrations compared to the survivors (p < 0.001). MiR-130a-3p was significantly downregulated during the intervention and correlated inversely with SIRT1 at baseline (r = −0.466, p = 0.007). Conclusion: The increased SIRT1 concentration after the SeQ₁₀ intervention associated with reduced CV mortality, partly mediated via miR-1303a-3p, suggests that SIRT1 is an additional mediator of the intervention, preventing vascular ageing. Full article

(This article belongs to the Section ROS, RNS and RSS)

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20 pages, 2668 KiB

Open AccessArticle

17β-Estradiol Suppresses Gastric Inflammatory and Apoptotic Stress Responses and Restores nNOS-Mediated Gastric Emptying in Streptozotocin (STZ)-Induced Diabetic Female Mice

by Jeremy Sprouse, Chethan Sampath and Pandu Gangula

Antioxidants 2023, 12(3), 758; https://doi.org/10.3390/antiox12030758 - 20 Mar 2023

Cited by 3 | Viewed by 1693

Abstract

Gastroparesis (Gp) is a severe complication of diabetes mellitus (DM) observed predominantly in women. It is characterized by abnormal gastric emptying (GE) without mechanical obstruction in the stomach. Nitric oxide (NO) is an inhibitory neurotransmitter produced by neuronal nitric oxide synthase (nNOS). It [...] Read more.

Gastroparesis (Gp) is a severe complication of diabetes mellitus (DM) observed predominantly in women. It is characterized by abnormal gastric emptying (GE) without mechanical obstruction in the stomach. Nitric oxide (NO) is an inhibitory neurotransmitter produced by neuronal nitric oxide synthase (nNOS). It plays a critical role in gastrointestinal (GI) motility and stomach emptying. Here, we wanted to demonstrate the protective effects of supplemental 17β-estradiol (E₂) on NO-mediated gastric function. We showed E₂ supplementation to alleviate oxidative and inflammatory stress in streptozotocin (STZ)-induced diabetic female mice. Our findings suggest that daily administration of E₂ at therapeutic doses is beneficial for metabolic homeostasis. This restoration occurs via regulating and modulating the expression/function of glycogen synthase kinase-3β (GSK-3β), nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), Phase II enzymes, MAPK- and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB)-mediated inflammatory cytokines (IL-1β, IL-6, TNFα, IGF-1), and gastric apoptotic regulators. We also showed E₂ supplementation to elevate GCH-1 protein levels in female diabetic mice. Since GCH-1 facilitates the production of tetrahydrobiopterin (BH₄, cofactor for nNOS), an increase in GCH-1 protein levels in diabetic mice may improve their GE and nitrergic function. Our findings provide new insights into the impact of estrogen on gastric oxidative stress and intracellular inflammatory cascades in the context of Gp. Full article

(This article belongs to the Special Issue Oxidative Stress in Diabetes and Complications)

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16 pages, 16304 KiB

Open AccessArticle

Safe-Shields: Basal and Anti-UV Protection of Human Keratinocytes by Redox-Active Cerium Oxide Nanoparticles Prevents UVB-Induced Mutagenesis

by Francesca Corsi, Erika Di Meo, Daniela Lulli, Greta Deidda Tarquini, Francesco Capradossi, Emanuele Bruni, Andrea Pelliccia, Enrico Traversa, Elena Dellambra, Cristina Maria Failla and Lina Ghibelli

Antioxidants 2023, 12(3), 757; https://doi.org/10.3390/antiox12030757 - 20 Mar 2023

Cited by 2 | Viewed by 1487

Abstract

Cerium oxide nanoparticles (nanoceria), biocompatible multifunctional nanozymes exerting unique biomimetic activities, mimic superoxide-dismutase and catalase through a self-regenerating, energy-free redox cycle driven by Ce^3+/4+ valence switch. Additional redox-independent UV-filter properties render nanoceria ideal multitask solar screens, shielding from UV exposure, simultaneously protecting [...] Read more.

Cerium oxide nanoparticles (nanoceria), biocompatible multifunctional nanozymes exerting unique biomimetic activities, mimic superoxide-dismutase and catalase through a self-regenerating, energy-free redox cycle driven by Ce^3+/4+ valence switch. Additional redox-independent UV-filter properties render nanoceria ideal multitask solar screens, shielding from UV exposure, simultaneously protecting tissues from UV-oxidative damage. Here, we report that nanoceria favour basal proliferation of primary normal keratinocytes, and protects them from UVB-induced DNA damage, mutagenesis, and apoptosis, minimizing cell loss and accelerating recovery with flawless cells. Similar cell-protective effects were found on irradiated noncancerous, but immortalized, p53-null HaCaT keratinocytes, with the notable exception that here, nanoceria do not accelerate basal HaCaT proliferation. Notably, nanoceria protect HaCaT from oxidative stress induced by irradiated titanium dioxide nanoparticles, a major active principle of commercial UV-shielding lotions, thus neutralizing their most critical side effects. The intriguing combination of nanoceria multiple beneficial properties opens the way for smart and safer containment measures of UV-induced skin damage and carcinogenesis. Full article

(This article belongs to the Special Issue Nanoantioxidants Volume II)

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12 pages, 353 KiB

Open AccessReview

Inhibition of Pyruvate Dehydrogenase in the Heart as an Initiating Event in the Development of Diabetic Cardiomyopathy

by Abdallah Elnwasany, Heba A. Ewida, Pamela A. Szweda and Luke I. Szweda

Antioxidants 2023, 12(3), 756; https://doi.org/10.3390/antiox12030756 - 20 Mar 2023

Cited by 2 | Viewed by 3497

Abstract

Obesity affects a growing fraction of the population and is a risk factor for type 2 diabetes and cardiovascular disease. Even in the absence of hypertension and coronary artery disease, type 2 diabetes can result in a heart disease termed diabetic cardiomyopathy. Diminished [...] Read more.

Obesity affects a growing fraction of the population and is a risk factor for type 2 diabetes and cardiovascular disease. Even in the absence of hypertension and coronary artery disease, type 2 diabetes can result in a heart disease termed diabetic cardiomyopathy. Diminished glucose oxidation, increased reliance on fatty acid oxidation for energy production, and oxidative stress are believed to play causal roles. However, the progression of metabolic changes and mechanisms by which these changes impact the heart have not been established. Cardiac pyruvate dehydrogenase (PDH), the central regulatory site for glucose oxidation, is rapidly inhibited in mice fed high dietary fat, a model of obesity and diabetes. Increased reliance on fatty acid oxidation for energy production, in turn, enhances mitochondrial pro-oxidant production. Inhibition of PDH may therefore initiate metabolic inflexibility and oxidative stress and precipitate diabetic cardiomyopathy. We discuss evidence from the literature that supports a role for PDH inhibition in loss in energy homeostasis and diastolic function in obese and diabetic humans and in rodent models. Finally, seemingly contradictory findings highlight the complexity of the disease and the need to delineate progressive changes in cardiac metabolism, the impact on myocardial structure and function, and the ability to intercede. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic Cardiomyopathy)

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16 pages, 2169 KiB

Open AccessArticle

Biodegradable Active Packaging Enriched with Essential Oils for Enhancing the Shelf Life of Strawberries

by Magdaléna Rusková, Alena Opálková Šišková, Katarína Mosnáčková, Custódia Gago, Adriana Guerreiro, Mária Bučková, Andrea Puškárová, Domenico Pangallo and Maria Dulce Antunes

Antioxidants 2023, 12(3), 755; https://doi.org/10.3390/antiox12030755 - 20 Mar 2023

Cited by 6 | Viewed by 2553

Abstract

The strawberry (Fragaria ananassa) is a nutrient-rich fruit with high content of health-beneficial compounds. However, strawberries are susceptible to mechanical damage and microbiological contamination which can cause changes in fruit sensory properties. These changes consequently effect on ripening and shelf life [...] Read more.

The strawberry (Fragaria ananassa) is a nutrient-rich fruit with high content of health-beneficial compounds. However, strawberries are susceptible to mechanical damage and microbiological contamination which can cause changes in fruit sensory properties. These changes consequently effect on ripening and shelf life of the strawberry. In recent years, essential oils (EOs) have been famous for their antimicrobial and antioxidant properties and are promising ecological alternatives to chemical antimicrobial substances. Nowadays, active packaging is one of several techniques developed for slowing down the metabolic processes of fresh fruits. Poly(lactic acid) (PLA) is one of the several polymers suitable for encapsulation EOs, whereas at the same time represent non-toxic, biodegradable, and compostable polymer derived from renewable resources. Suitable packaging prolongs the shelf life of fruit, keeps the products at the highest possible nutrition level, improves quality, and attracts customer attention. In the current study, we encapsulated EOs (lemongrass and oregano) into a PLA and poly(3-hydroxybutyrate) (PHB) packaging film and explored their antimicrobial and antioxidant properties. Moreover, biochemical and quality parameters for strawberry preservation and shelf-life extension were also assessed. Our tested active packaging film with EOs was proven to be useful for postharvest quality maintenance and shelf-life extension of strawberries, with PLA/PHB/ATBC + 5% lemongrass EO being slightly better than PLA/PHB/ATBC + 5% oregano EO. Full article

(This article belongs to the Special Issue Antioxidant Activity of Essential Oils, 2nd Edition)

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18 pages, 2193 KiB

Open AccessArticle

Beyond Antioxidant Activity: Redox Properties of Catechins May Affect Changes in the DNA Methylation Profile—The Example of SRXN1 Gene

by Patrycja Jakubek, Jovana Rajić, Monika Kuczyńska, Klaudia Suliborska, Mateusz Heldt, Karol Dziedziul, Melita Vidaković, Jacek Namieśnik and Agnieszka Bartoszek

Antioxidants 2023, 12(3), 754; https://doi.org/10.3390/antiox12030754 - 20 Mar 2023

Cited by 4 | Viewed by 1452

Abstract

The role of catechins in the epigenetic regulation of gene expression has been widely studied; however, if and how this phenomenon relates to the redox properties of these polyphenols remains unknown. Our earlier study demonstrated that exposure of the human colon adenocarcinoma HT29 [...] Read more.

The role of catechins in the epigenetic regulation of gene expression has been widely studied; however, if and how this phenomenon relates to the redox properties of these polyphenols remains unknown. Our earlier study demonstrated that exposure of the human colon adenocarcinoma HT29 cell line to these antioxidants affects the expression of redox-related genes. In particular, treatment with (−)-epigallocatechin (EGC) downregulated transcription of gene encoding sulfiredoxin-1 (SRXN1), the peroxidase involved in the protection of cells against hydrogen peroxide-induced oxidative stress. The aim of this study was to investigate whether the observed SRXN1 downregulation was accompanied by changes in the DNA methylation level of its promoter and, if so, whether it was correlated with the redox properties of catechins. The impact on DNA methylation profile in HT29 cells treated with different concentrations of five catechins, varying in chemical structures and standard reduction potentials as well as susceptibility to oxidation, was monitored by a methylation-sensitive high-resolution melting technique employing the SRXN1 promoter region as a model target. We demonstrated that catechins, indeed, are able to modulate DNA methylation of the SRXN1 gene in a redox-related manner. The nonlinear method in the statistical analysis made it possible to fish out two parameters (charge transfer in oxidation process Q_ox and time of electron transfer t), whose strong interactions correlated with observed modulation of DNA methylation by catechins. Based on these findings, we present a proof-of-concept that DNA methylation, which limits SRXN1 expression and thus restricts the multidirectional antioxidant action of SRXN1, may represent a mechanism protecting cells against reductive stress caused by particularly fast-reacting reductants such as EGC and (−)-epicatechin gallate (ECG) in our study. Full article

(This article belongs to the Special Issue Something is Rotten in the State of Redox)

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23 pages, 2094 KiB

Open AccessReview

Nitric Oxide/Nitric Oxide Synthase System in the Pathogenesis of Neurodegenerative Disorders—An Overview

by Olga-Maria Iova, Gheorghe-Eduard Marin, Izabella Lazar, Ioana Stanescu, Gabriela Dogaru, Cristina Ariadna Nicula and Adriana Elena Bulboacă

Antioxidants 2023, 12(3), 753; https://doi.org/10.3390/antiox12030753 - 20 Mar 2023

Cited by 11 | Viewed by 3117

Abstract

Nitric oxide, a ubiquitous molecule found throughout the natural world, is a key molecule implicated in many central and benefic molecular pathways and has a well-established role in the function of the central nervous system, as numerous studies have previously shown. Dysregulation of [...] Read more.

Nitric oxide, a ubiquitous molecule found throughout the natural world, is a key molecule implicated in many central and benefic molecular pathways and has a well-established role in the function of the central nervous system, as numerous studies have previously shown. Dysregulation of its metabolism, mainly the upregulation of nitric oxide production, has been proposed as a trigger and/or aggravator for many neurological affections. Increasing evidence supports the implication of this molecule in prevalent neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, or amyotrophic lateral sclerosis. The mechanisms proposed for its neurotoxicity mainly center around the increased quantities of nitric oxide that are produced in the brain, their cause, and, most importantly, the pathological metabolic cascades created. These cascades lead to the formation of neuronal toxic substances that impair the neurons’ function and structure on multiple levels. The purpose of this review is to present the main causes of increased pathological production, as well as the most important pathophysiological mechanisms triggered by nitric oxide, mechanisms that could help explain a part of the complex picture of neurodegenerative diseases and help develop targeted therapies. Full article

(This article belongs to the Special Issue Advances for the NO/NOS System)

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16 pages, 2728 KiB

Open AccessSystematic Review

The Impact of a Very Short Abstinence Period on Assisted Reproductive Technique Outcomes: A Systematic Review and Meta-Analysis

by Federica Barbagallo, Rossella Cannarella, Andrea Crafa, Sandro La Vignera, Rosita A. Condorelli, Claudio Manna and Aldo E. Calogero

Antioxidants 2023, 12(3), 752; https://doi.org/10.3390/antiox12030752 - 20 Mar 2023

Cited by 4 | Viewed by 2602

Abstract

Background: Previous studies supported the beneficial effects of a very short abstinence period on sperm quality. This systematic review and meta-analysis aimed to evaluate the effects of a very short abstinence period (within 4 h) on assisted reproductive technique (ART) outcomes. Methods: A [...] Read more.

Background: Previous studies supported the beneficial effects of a very short abstinence period on sperm quality. This systematic review and meta-analysis aimed to evaluate the effects of a very short abstinence period (within 4 h) on assisted reproductive technique (ART) outcomes. Methods: A literature search was performed using the Pubmed, Scopus, Web of Science, and Cochrane databases. A meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) for randomized controlled trials (RCTs). All eligible studies were selected following the PICOS (Population, Intervention, Comparison/Comparator, Outcomes, Study type) model. The following pregnancy outcomes after ART were considered: fertilization rate (FR), implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR). This study was registered on PROSPERO (CRD42023396429). Results: We evaluated 414 records for eligibility, and 7 studies were ultimately included. Our analysis showed that a very short abstinence period significantly increased the IR, CPR, and LBR after ART. No significant differences were found for the FR and MR. Conclusions: A second ejaculation collected very shortly after the first one could represent a simple strategy to improve the results of ART, especially in couples including patients with abnormal sperm parameters. Full article

(This article belongs to the Special Issue Role of Oxidative Stress and Inflammation in Maternal-Perinatal Well-Being)

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29 pages, 1857 KiB

Open AccessArticle

Combined Intake of Fish Oil and D-Fagomine Prevents High-Fat High-Sucrose Diet-Induced Prediabetes by Modulating Lipotoxicity and Protein Carbonylation in the Kidney

by Lucía Méndez, Silvia Muñoz, Lorena Barros, Bernat Miralles-Pérez, Marta Romeu, Sara Ramos-Romero, Josep Lluís Torres and Isabel Medina

Antioxidants 2023, 12(3), 751; https://doi.org/10.3390/antiox12030751 - 19 Mar 2023

Cited by 3 | Viewed by 1567

Abstract

Obesity has been recognized as a major risk factor for chronic kidney disease, insulin resistance being an early common metabolic feature in patients suffering from this syndrome. This study aims to investigate the mechanism underlying the induction of kidney dysfunction and the concomitant [...] Read more.

Obesity has been recognized as a major risk factor for chronic kidney disease, insulin resistance being an early common metabolic feature in patients suffering from this syndrome. This study aims to investigate the mechanism underlying the induction of kidney dysfunction and the concomitant onset of insulin resistance by long-term high-fat and sucrose diet feeding in Sprague Dawley rats. To achieve this goal, our study analyzed renal carbonylated protein patterns, ectopic lipid accumulation and fatty acid profiles and correlated them with biometrical and biochemical measurements and other body redox status parameters. Rats fed the obesogenic diet developed a prediabetic state and incipient kidney dysfunction manifested in increased plasma urea concentration and superior levels of renal fat deposition and protein carbonylation. An obesogenic diet increased renal fat by preferentially promoting the accumulation of saturated fat, arachidonic, and docosahexaenoic fatty acids while decreasing oleic acid. Renal lipotoxicity was accompanied by selectively higher carbonylation of proteins involved in the blood pH regulation, i.e., bicarbonate reclamation and synthesis, amino acid, and glucose metabolisms, directly related to the onset of insulin resistance. This study also tested the combination of antioxidant properties of fish oil with the anti-diabetic properties of buckwheat D-Fagomine to counteract diet-induced renal alterations. Results demonstrated that bioactive compounds combined attenuated lipotoxicity, induced more favorable lipid profiles and counteracted the excessive carbonylation of proteins associated with pH regulation in the kidneys, resulting in an inhibition of the progression of the prediabetes state and kidney disease. Full article

(This article belongs to the Special Issue Natural Antioxidants in Obesity and Related Diseases)

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Antioxidants, Volume 12, Issue 3 (March 2023) – 244 articles

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