Antioxidants

22 pages, 1081 KiB

Open AccessArticle

Oxidative Stress in Patients with Advanced CKD and Renal Replacement Therapy: The Key Role of Peripheral Blood Leukocytes

by Carmen Vida, Carlos Oliva, Claudia Yuste, Noemí Ceprián, Paula Jara Caro, Gemma Valera, Ignacio González de Pablos, Enrique Morales and Julia Carracedo

Antioxidants 2021, 10(7), 1155; https://doi.org/10.3390/antiox10071155 - 20 Jul 2021

Cited by 11 | Viewed by 3330

Abstract

Oxidative stress plays a key role in the pathophysiology of chronic kidney disease (CKD). Most studies have investigated peripheral redox state focus on plasma, but not in different immune cells. Our study analyzed several redox state markers in plasma and isolated peripheral polymorphonuclear [...] Read more.

Oxidative stress plays a key role in the pathophysiology of chronic kidney disease (CKD). Most studies have investigated peripheral redox state focus on plasma, but not in different immune cells. Our study analyzed several redox state markers in plasma and isolated peripheral polymorphonuclear (PMNs) and mononuclear (MNs) leukocytes from advanced-CKD patients, also evaluating differences of hemodialysis (HD) and peritoneal dialysis (PD) procedures. Antioxidant (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH)) and oxidant parameters (xanthine oxidase (XO), oxidized glutathione (GSSG), malondialdehyde (MDA)) were assessed in plasma, PMNs and MNs from non-dialysis-dependent-CKD (NDD-CKD), HD and PD patients and healthy controls. Increased oxidative stress and damage were observed in plasma, PMNs and MNs from NDD-CKD, HD and PD patients (increased XO, GSSG and MDA; decreased SOD, CAT, GPX and GSH; altered GSSG/GSH balance). Several oxidative alterations were more exacerbated in PMNs, whereas others were only observed in MNs. Dialysis procedures had a positive effect on preserving the GSSG/GSH balance in PMNs. Interestingly, PD patients showed greater oxidative stress than HD patients, especially in MNs. The assessment of redox state parameters in PMNs and MNs could have potential use as biomarkers of the CKD progression. 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 II)

► Show Figures

Graphical abstract

24 pages, 1469 KiB

Open AccessReview

Impact of Oxidative Stress on Male Reproduction in Domestic and Wild Animals

by Eliana Pintus and José Luis Ros-Santaella

Antioxidants 2021, 10(7), 1154; https://doi.org/10.3390/antiox10071154 - 20 Jul 2021

Cited by 56 | Viewed by 4841

Abstract

Oxidative stress occurs when the levels of reactive oxygen species (ROS) overcome the antioxidant defenses of the organism, jeopardizing several biological functions, including reproduction. In the male reproductive system, oxidative stress not only impairs sperm fertility but also compromises offspring health and survival, [...] Read more.

Oxidative stress occurs when the levels of reactive oxygen species (ROS) overcome the antioxidant defenses of the organism, jeopardizing several biological functions, including reproduction. In the male reproductive system, oxidative stress not only impairs sperm fertility but also compromises offspring health and survival, inducing oxidative damage to lipids, proteins and nucleic acids. Although a clear link between oxidative stress and male fertility disorders has been demonstrated in humans and laboratory rodents, little information is available about the implications of impaired redox homeostasis in the male fertility of domestic and wild animals. Therefore, this review aims to provide an update regarding the intrinsic and extrinsic factors that are associated with oxidative stress in the male reproductive system and their impact on the reproductive performance of domestic and wild animals. The most recent strategies for palliating the detrimental effects of oxidative stress on male fertility are reviewed together with their potential economic and ecological implications in the livestock industry and biodiversity conservation. Full article

(This article belongs to the Special Issue Redox Signal in the Reproductive System)

► Show Figures

Figure 1

12 pages, 1308 KiB

Open AccessArticle

β-Hydroxybutyrate, a Ketone Body, Potentiates the Antioxidant Defense via Thioredoxin 1 Upregulation in Cardiomyocytes

by Shin-ichi Oka, Fan Tang, Adave Chin, Guersom Ralda, Xiaoyong Xu, Chengchen Hu, Zhi Yang, Maha Abdellatif and Junichi Sadoshima

Antioxidants 2021, 10(7), 1153; https://doi.org/10.3390/antiox10071153 - 20 Jul 2021

Cited by 13 | Viewed by 3537

Abstract

Thioredoxin 1 (Trx1) is a major antioxidant that acts adaptively to protect the heart during the development of diabetic cardiomyopathy. The molecular mechanism(s) responsible for regulating the Trx1 level and/or activity during diabetic cardiomyopathy is unknown. β-hydroxybutyrate (βHB), a major ketone body in [...] Read more.

Thioredoxin 1 (Trx1) is a major antioxidant that acts adaptively to protect the heart during the development of diabetic cardiomyopathy. The molecular mechanism(s) responsible for regulating the Trx1 level and/or activity during diabetic cardiomyopathy is unknown. β-hydroxybutyrate (βHB), a major ketone body in mammals, acts as an alternative energy source in cardiomyocytes under stress, but it also appears to be involved in additional mechanisms that protect the heart against stress. βHB upregulated Trx1 in primary cultured cardiomyocytes in a dose- and a time-dependent manner and a ketogenic diet upregulated Trx1 in the heart. βHB protected cardiomyocytes against H₂O₂-induced death, an effect that was abolished in the presence of Trx1 knockdown. βHB also alleviated the H₂O₂-induced inhibition of mTOR and AMPK, known targets of Trx1, in a Trx1-dependent manner, suggesting that βHB potentiates Trx1 function. It has been shown that βHB is a natural inhibitor of HDAC1 and knockdown of HDAC1 upregulated Trx1 in cardiomyocytes, suggesting that βHB may upregulate Trx1 through HDAC inhibition. βHB induced Trx1 acetylation and inhibited Trx1 degradation, suggesting that βHB-induced inhibition of HDAC1 may stabilize Trx1 through protein acetylation. These results suggest that βHB potentiates the antioxidant defense in cardiomyocytes through the inhibition of HDAC1 and the increased acetylation and consequent stabilization of Trx1. Thus, modest upregulation of ketone bodies in diabetic hearts may protect the heart through the upregulation of Trx1. Full article

(This article belongs to the Special Issue Antioxidants in Diabetes)

► Show Figures

Graphical abstract

29 pages, 496 KiB

Open AccessReview

The Coronavirus Disease 2019 (COVID-19): Key Emphasis on Melatonin Safety and Therapeutic Efficacy

by Eva Ramos, Francisco López-Muñoz, Emilio Gil-Martín, Javier Egea, Iris Álvarez-Merz, Sakshi Painuli, Prabhakar Semwal, Natália Martins, Jesús M. Hernández-Guijo and Alejandro Romero

Antioxidants 2021, 10(7), 1152; https://doi.org/10.3390/antiox10071152 - 20 Jul 2021

Cited by 20 | Viewed by 7171

Abstract

Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune [...] Read more.

Viral infections constitute a tectonic convulsion in the normophysiology of the hosts. The current coronavirus disease 2019 (COVID-19) pandemic is not an exception, and therefore the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, like any other invading microbe, enacts a generalized immune response once the virus contacts the body. Melatonin is a systemic dealer that does not overlook any homeostasis disturbance, which consequently brings into play its cooperative triad, antioxidant, anti-inflammatory, and immune-stimulant backbone, to stop the infective cycle of SARS-CoV-2 or any other endogenous or exogenous threat. In COVID-19, the corporal propagation of SARS-CoV-2 involves an exacerbated oxidative activity and therefore the overproduction of great amounts of reactive oxygen and nitrogen species (RONS). The endorsement of melatonin as a possible protective agent against the current pandemic is indirectly supported by its widely demonstrated beneficial role in preclinical and clinical studies of other respiratory diseases. In addition, focusing the therapeutic action on strengthening the host protection responses in critical phases of the infective cycle makes it likely that multi-tasking melatonin will provide multi-protection, maintaining its efficacy against the virus variants that are already emerging and will emerge as long as SARS-CoV-2 continues to circulate among us. Full article

(This article belongs to the Special Issue Melatonin and Related Compounds: Antioxidant and Anti-inflammatory Actions)

15 pages, 14012 KiB

Open AccessArticle

Determination of Bioactive Compounds in Sequential Extracts of Chia Leaf (Salvia hispanica L.) Using UHPLC-HRMS (Q-Orbitrap) and a Global Evaluation of Antioxidant In Vitro Capacity

by María Carolina Zúñiga-López, Gabriela Maturana, Guillem Campmajó, Javier Saurina and Oscar Núñez

Antioxidants 2021, 10(7), 1151; https://doi.org/10.3390/antiox10071151 - 20 Jul 2021

Cited by 16 | Viewed by 3031

Abstract

Consumers’ interest in foods that are nutritionally balanced and with health benefits has increased. The food industry is paying attention to the use of the ancestral seed Salvia hispanica L., commonly known as chia. At present, only chia seeds, which are a natural [...] Read more.

Consumers’ interest in foods that are nutritionally balanced and with health benefits has increased. The food industry is paying attention to the use of the ancestral seed Salvia hispanica L., commonly known as chia. At present, only chia seeds, which are a natural source of omega-3 and omega-6, fiber, proteins, and natural antioxidants, are commercialized. Although some studies reveal the presence of several bioactive compounds, such as polyphenols (e.g., vitexin, orientin, and some hydroxycinnamic acids) in chia leaf methanolic extracts, the chia plant is commonly used as fertilizer or treated as waste after harvest. Therefore, it can represent a by-product that could be considered a great source of bioactive compounds with unexplored potential in medicine and food industry applications. In this work, UHPLC-HRMS (Q-Orbitrap) was employed to tentatively identify and determine the bioactive compounds present in different leaf extracts of chia plants of black and white seed phenotype obtained with solvents of different polarity (ethanol, ethyl acetate, dichloromethane, and hexane) to address chia plant by-product revalorization. The chemical antioxidant capacity was also studied and correlated to the found bioactive compounds. In these experiments, black chia showed a higher antioxidant capacity than white chia in the ethanolic extracts. Moreover, experiments on cellular antioxidant activity were also performed with a predominance of the white chia extract. It is noted that the cellular antioxidant activity results make chia ethanolic extracts promising antioxidants. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Vegetables and Foods)

► Show Figures

Figure 1

25 pages, 2175 KiB

Open AccessArticle

Olive Pomace Phenolic Compounds and Extracts Can Inhibit Inflammatory- and Oxidative-Related Diseases of Human Ocular Surface Epithelium

by Nikolaos Katsinas, Soraya Rodríguez-Rojo and Amalia Enríquez-de-Salamanca

Antioxidants 2021, 10(7), 1150; https://doi.org/10.3390/antiox10071150 - 20 Jul 2021

Cited by 13 | Viewed by 3450

Abstract

Oxidative- and inflammatory-related ocular surface diseases have high prevalence and are an emerging issue in ophthalmology. Olive pomace (OP) is the olive oil’s industry main by-product, and is potentially environmentally hazardous. Nevertheless, it contains phenolic compounds with important bioactivities, like oleuropein (OL) and [...] Read more.

Oxidative- and inflammatory-related ocular surface diseases have high prevalence and are an emerging issue in ophthalmology. Olive pomace (OP) is the olive oil’s industry main by-product, and is potentially environmentally hazardous. Nevertheless, it contains phenolic compounds with important bioactivities, like oleuropein (OL) and hydroxytyrosol (HT). The antioxidant and anti-inflammatory effects of four OP extracts (CONV, OPT(1–3)), pure OL and HT, and mixtures thereof were screened on human corneal (HCE) and conjunctival epithelial (IM-ConjEpi) cells. CONV was conventionally extracted, while OPT(1–3) were produced by pressurized liquid extraction. Thanks to their improved activity, CONV and OPT3 (HT-enriched) were selected for dose-dependent studies. Cells were stimulated with tumor necrosis factor-α or ultraviolet-B radiation, measuring interleukin (IL)-1β, IL-6, IL-8, and IL-17A as well as interferon γ-induced protein [IP]-10 secretion or intracellular ROS production, respectively. On HCE, both extracts and HT inhibited the secretion of most measured ILs, demonstrating a strong anti-inflammatory effect; while in IM-ConjEpi, all samples decreased IP-10 secretion. Moreover, HT, OL, and both extracts showed strong dose-dependent antioxidant activity in both cell lines. Compared with CONV, OPT3 was active at lower concentrations, demonstrating that intensified extraction techniques are selective towards targeted biomarkers. Hence, a high-value application as potential ocular surface therapy was proposed for the OP valorization. Full article

(This article belongs to the Special Issue Intensification Technologies to Efficiently Extract Antioxidants from Agro-Food Residues)

► Show Figures

Figure 1

12 pages, 3982 KiB

Open AccessCommunication

Reactive Species from Two-Signal Activated Macrophages Interfere with Their Oxygen Consumption Measurements

by Panagiotis F. Christopoulos, Mantas Grigalavicius, Alexandre Corthay, Kristian Berg and Theodossis A. Theodossiou

Antioxidants 2021, 10(7), 1149; https://doi.org/10.3390/antiox10071149 - 20 Jul 2021

Cited by 1 | Viewed by 2740

Abstract

Metabolic modulation of macrophage activation has emerged as a promising strategy lately in immunotherapeutics. However, macrophages have a broad spectrum of functions and thus, understanding the exact metabolic changes that drive a particular immune response, is of major importance. In our previous work, [...] Read more.

Metabolic modulation of macrophage activation has emerged as a promising strategy lately in immunotherapeutics. However, macrophages have a broad spectrum of functions and thus, understanding the exact metabolic changes that drive a particular immune response, is of major importance. In our previous work, we have reported a key role of nitric oxide (NO^●) in two(2)-signal activated macrophages [M(2-signals)]. Further characterization using metabolic analysis in intact cells, showed that the basal and maximal respiration levels of M(2-signals) were comparable, with cells being unresponsive to the injections-inducd mitochondrial stress. Here, we show that excessive NO^● secretion by the M(2-signals) macrophages, interferes with the oxygen (O₂) consumption measurements on cells using the seahorse metabolic analyzer. This is attributed mainly to the consumption of ambient oxygen by NO^● to form NO₂⁻ and/or NO₃⁻ but also to the reduction of O₂ to superoxide anion (O₂^●−) by stray electrons from the electron transport chain, leading to the formation of peroxynitrite (ONOO⁻). We found that reactive species-donors in the absence of cells, produce comparable oxygen consumption rates (OCR) with M(2-signals) macrophages. Furthermore, inhibition of NO^● production, partly recovered the respiration of activated macrophages, while external addition of NO^● in non-activated macrophages downregulated their OCR levels. Our findings are crucial for the accurate metabolic characterization of cells, especially in cases where reactive nitrogen or oxygen species are produced in excess. Full article

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

► Show Figures

Figure 1

16 pages, 2855 KiB

Open AccessArticle

Atypical Bacilliredoxin AbxC Plays a Role in Responding to Oxidative Stress in Radiation-Resistant Bacterium Deinococcus radiodurans

by Soyoung Jeong, Jong-Hyun Jung, Min-Kyu Kim, Arjan de Groot, Laurence Blanchard, Sangryeol Ryu, Yong-Sun Bahn and Sangyong Lim

Antioxidants 2021, 10(7), 1148; https://doi.org/10.3390/antiox10071148 - 20 Jul 2021

Cited by 4 | Viewed by 2521

Abstract

Deinococcus radiodurans is a robust bacterium with extraordinary resistance to ionizing radiation and reactive oxygen species (ROS). D. radiodurans produces an antioxidant thiol compound called bacillithiol (BSH), but BSH-related enzymes have not been investigated. The D. radiodurans mutant lacking bshA (dr_ [...] Read more.

Deinococcus radiodurans is a robust bacterium with extraordinary resistance to ionizing radiation and reactive oxygen species (ROS). D. radiodurans produces an antioxidant thiol compound called bacillithiol (BSH), but BSH-related enzymes have not been investigated. The D. radiodurans mutant lacking bshA (dr_1555), the first gene of the BSH biosynthetic pathway, was devoid of BSH and sensitive to hydrogen peroxide (H₂O₂) compared to the wild-type D. radiodurans strain. Three bacilliredoxin (Brx) proteins, BrxA, B, and C, have been identified in BSH-producing bacteria, such as Bacillus. D. radiodurans possesses DR_1832, a putative homolog of BrxC. However, because DR_1832 contains a novel signature motif (TCHKT) and a C-terminal region similar to the colicin-like immunity domain, we named it AbxC (atypical BrxC). The deletion of abxC also sensitized cells to H₂O₂. AbxC exhibited peroxidase activity in vitro, which was linked to nicotinamide adenine dinucleotide phosphate (NADPH) oxidation via the BSH disulfide reductase DR_2623 (DrBdr). AbxC proteins were present mainly as dimers after exposure to H₂O₂ in vitro, and the oxidized dimers were resolved to monomers by the reaction coupled with BSH as an electron donor, in which DrBdr transported reducing equivalents from NADPH to AbxC through BSH recycling. We identified 25 D. radiodurans proteins that potentially interact with AbxC using AbxC-affinity chromatography. Most of them are associated with cellular metabolisms, such as glycolysis and amino acid biosynthesis, and stress response. Interestingly, AbxC could bind to the proposed peroxide-sensing transcription regulator, DrOxyR. These results suggest that AbxC may be involved in the H₂O₂ signaling mechanism mediated by DrOxyR. Full article

(This article belongs to the Special Issue Redox Biology in Microorganisms)

► Show Figures

Figure 1

15 pages, 2555 KiB

Open AccessArticle

Neuroprotective Effect of 4-Phenylbutyric Acid against Photo-Stress in the Retina

by Naymel Alejandra Guzmán Mendoza, Kohei Homma, Hideto Osada, Eriko Toda, Norimitsu Ban, Norihiro Nagai, Kazuno Negishi, Kazuo Tsubota and Yoko Ozawa

Antioxidants 2021, 10(7), 1147; https://doi.org/10.3390/antiox10071147 - 20 Jul 2021

Cited by 9 | Viewed by 2943

Abstract

Exposure to excessive visible light causes retinal degeneration and may influence the progression of retinal blinding diseases. However, there are currently no applied treatments. Here, we focused on endoplasmic reticulum (ER) stress, which can cause cellular degeneration and apoptosis in response to stress. [...] Read more.

Exposure to excessive visible light causes retinal degeneration and may influence the progression of retinal blinding diseases. However, there are currently no applied treatments. Here, we focused on endoplasmic reticulum (ER) stress, which can cause cellular degeneration and apoptosis in response to stress. We analyzed functional, histological, and molecular changes in the light-exposed retina and the effects of administering an ER-stress inhibitor, 4-phenylbutyric acid (4-PBA), in mice. We found that light-induced visual function impairment related to photoreceptor cell loss and outer segment degeneration were substantially suppressed by 4-PBA administration, following attenuated photoreceptor apoptosis. Induction of retinal ER stress soon after light exposure, represented by upregulation of the immunoglobulin heavy chain binding protein (BiP) and C/EBP-Homologous Protein (CHOP), were suppressed by 4-PBA. Concurrently, light-induced oxidative stress markers, Nuclear factor erythroid 2–related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1), and mitochondrial apoptotic markers, B-cell lymphoma 2 apoptosis regulator (Bcl-2)-associated death promoter (Bad), and Bcl-2-associated X protein (Bax), were suppressed by 4-PBA administration. Increased expression of glial fibrillary acidic protein denoted retinal neuroinflammation, and inflammatory cytokines were induced after light exposure; however, 4-PBA acted as an anti-inflammatory. Suppression of ER stress by 4-PBA may be a new therapeutic approach to suppress the progression of retinal neurodegeneration and protect visual function against photo-stress. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Health and Diseases)

► Show Figures

Figure 1

21 pages, 1543 KiB

Open AccessReview

Mechanisms of Ataxia Telangiectasia Mutated (ATM) Control in the DNA Damage Response to Oxidative Stress, Epigenetic Regulation, and Persistent Innate Immune Suppression Following Sepsis

by Laura A. Huff, Shan Yan and Mark G. Clemens

Antioxidants 2021, 10(7), 1146; https://doi.org/10.3390/antiox10071146 - 20 Jul 2021

Cited by 8 | Viewed by 3847

Abstract

Cells have evolved extensive signaling mechanisms to maintain redox homeostasis. While basal levels of oxidants are critical for normal signaling, a tipping point is reached when the level of oxidant species exceed cellular antioxidant capabilities. Myriad pathological conditions are characterized by elevated oxidative [...] Read more.

Cells have evolved extensive signaling mechanisms to maintain redox homeostasis. While basal levels of oxidants are critical for normal signaling, a tipping point is reached when the level of oxidant species exceed cellular antioxidant capabilities. Myriad pathological conditions are characterized by elevated oxidative stress, which can cause alterations in cellular operations and damage to cellular components including nucleic acids. Maintenance of nuclear chromatin are critically important for host survival and eukaryotic organisms possess an elaborately orchestrated response to initiate repair of such DNA damage. Recent evidence indicates links between the cellular antioxidant response, the DNA damage response (DDR), and the epigenetic status of the cell under conditions of elevated oxidative stress. In this emerging model, the cellular response to excessive oxidants may include redox sensors that regulate both the DDR and an orchestrated change to the epigenome in a tightly controlled program that both protects and regulates the nuclear genome. Herein we use sepsis as a model of an inflammatory pathophysiological condition that results in elevated oxidative stress, upregulation of the DDR, and epigenetic reprogramming of hematopoietic stem cells (HSCs) to discuss new evidence for interplay between the antioxidant response, the DNA damage response, and epigenetic status. Full article

(This article belongs to the Special Issue Cellular and Molecular Regulation of Genomic and Epigenetic Integrity by ROS/RNS)

► Show Figures

Graphical abstract

20 pages, 4149 KiB

Open AccessArticle

Purification, Physicochemical Properties, and Antioxidant Activities of Two Low-Molecular-Weight Polysaccharides from Ganoderma leucocontextum Fruiting Bodies

by Xiong Gao, Jiayi Qi, Chi-Tang Ho, Bin Li, Yizhen Xie, Shaodan Chen, Huiping Hu, Zhongzheng Chen and Qingping Wu

Antioxidants 2021, 10(7), 1145; https://doi.org/10.3390/antiox10071145 - 20 Jul 2021

Cited by 19 | Viewed by 3620

Abstract

Two low-molecular-weight polysaccharides (GLP-1 and GLP-2) were purified from Ganoderma leucocontextum fruiting bodies, and their physicochemical properties and antioxidant activities were investigated and compared in this study. The results showed that GLP-1 and GLP-2 were mainly composed of mannose, glucose, galactose, xylose, and [...] Read more.

Two low-molecular-weight polysaccharides (GLP-1 and GLP-2) were purified from Ganoderma leucocontextum fruiting bodies, and their physicochemical properties and antioxidant activities were investigated and compared in this study. The results showed that GLP-1 and GLP-2 were mainly composed of mannose, glucose, galactose, xylose, and arabinose, with weight-average molecular weights of 6.31 and 14.07 kDa, respectively. Additionally, GLP-1 and GLP-2 had a similar chain conformation, crystal structure, and molecular surface morphology. Moreover, GLP-1 exhibited stronger antioxidant activities than GLP-2 in five different assays: 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), hydroxyl radical, superoxide anion radical, ferric reducing antioxidant power (FRAP), and oxygen radical antioxidant capacity (ORAC). The main linkage types of GLP-1 were found to be →4)-α-D-Glcp-(1→, →4)-β-D-Glcp-(1→, →3)-β-D-Glcp-(1→, →6)-β-D-Galp-(1→, →6)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, and Glcp-(1→ by methylation analysis and nuclear magnetic resonance (NMR) spectroscopy. In addition, GLP-1 could protect NIH3T3 cells against tert-butyl hydroperoxide (tBHP)-induced oxidative damage by increasing catalase (CAT) and glutathione peroxidase (GSH-Px) activities, elevating the glutathione/oxidized glutathione (GSH/GSSG) ratio, and decreasing the malondialdehyde (MDA) level. These findings indicated that GLP-1 could be explored as a potential antioxidant agent for application in functional foods. Full article

(This article belongs to the Special Issue Natural Products Targeting on Oxidative Stress-Related Diseases)

► Show Figures

Figure 1

27 pages, 14897 KiB

Open AccessArticle

In Vitro Anticancer Activity and Oxidative Stress Biomarkers Status Determined by Usnea barbata (L.) F.H. Wigg. Dry Extracts

by Violeta Popovici, Laura Bucur, Gabriela Vochita, Daniela Gherghel, Cosmin Teodor Mihai, Dan Rambu, Suzana Ioana Calcan, Teodor Costache, Iulia Elena Cucolea, Elena Matei, Florin Ciprian Badea, Aureliana Caraiane and Victoria Badea

Antioxidants 2021, 10(7), 1141; https://doi.org/10.3390/antiox10071141 - 20 Jul 2021

Cited by 19 | Viewed by 5257

Abstract

Lichens represent an important resource for common traditional medicines due to their numerous metabolites that can exert diverse pharmacological activities including anticancer effects. To find new anticancer compounds with fewer side effects and low tumor resistance, a bioprospective study of Usnea barbata (L.) [...] Read more.

Lichens represent an important resource for common traditional medicines due to their numerous metabolites that can exert diverse pharmacological activities including anticancer effects. To find new anticancer compounds with fewer side effects and low tumor resistance, a bioprospective study of Usnea barbata (L.) F.H. Wigg. (U. barbata), a lichen from the Călimani Mountains (Suceava county, Romania) was performed. The aim of this research was to investigate the anticancer potential, morphologic changes, wound healing property, clonogenesis, and oxidative stress biomarker status of four extracts of U. barbata in different solvents (methanol, ethanol, acetone, and ethyl acetate), and also of usnic acid (UA) as a positive control on the CAL-27 (ATCC^® CRL-2095™) oral squamous carcinoma (OSCC) cell line and V79 (ATCC^® CCL-93™) lung fibroblasts as normal cells. Using the MTT assay and according to IC₅₀ values, it was found that the most potent anticancer property was displayed by acetone and ethyl acetate extracts. All U. barbata extracts determined morphological modifications (losing adhesion capacity, membrane shrinkage, formation of abnormal cellular wrinkles, and vacuolization) with higher intensity in tumor cells than in normal ones. The most intense anti-migration effect was established in the acetone extract treatment. The clonogenic assay showed that some U. barbata extracts decreased the ability of cancer cells to form colonies compared to untreated cells, suggesting a potential anti-tumorigenic property of the tested extracts. Therefore, all the U. barbata extracts manifest anticancer activity of different intensity, based, at least partially, on an imbalance in antioxidant defense mechanisms, causing oxidative stress. Full article

(This article belongs to the Special Issue Anticancer Antioxidants)

► Show Figures

Figure 1

18 pages, 8645 KiB

Open AccessArticle

Comparison of Phenolic Contents and Scavenging Activities of Miang Extracts Derived from Filamentous and Non-Filamentous Fungi-Based Fermentation Processes

by Aliyu Dantani Abdullahi, Pratthana Kodchasee, Kridsada Unban, Thanawat Pattananandecha, Chalermpong Saenjum, Apinun Kanpiengjai, Kalidas Shetty and Chartchai Khanongnuch

Antioxidants 2021, 10(7), 1144; https://doi.org/10.3390/antiox10071144 - 19 Jul 2021

Cited by 11 | Viewed by 3081

Abstract

The study investigated the impact of the fermentation process on the phenolic contents and antioxidant and anti-inflammatory activities in extracts of Miang, an ethnic fermented tea product of northern Thailand. The acetone (80%) extraction of Miang samples fermented by a non-filamentous fungi-based process [...] Read more.

The study investigated the impact of the fermentation process on the phenolic contents and antioxidant and anti-inflammatory activities in extracts of Miang, an ethnic fermented tea product of northern Thailand. The acetone (80%) extraction of Miang samples fermented by a non-filamentous fungi-based process (NFP) and filamentous fungi-based process (FFP) had elevated levels of total polyphenols, total tannins, and condensed tannins compared to young and mature tea leaves. The antioxidant studies also showed better the half-maximal inhibitory concentration (IC₅₀) values for fermented leaves in both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity assays as well as improved ferric reducing antioxidant power (FRAP) compared to young and mature tea leaves. Extracts of NFP and FFP samples at concentrations of 50 and 100 ppm showed better protective effects against hydrogen peroxide (H₂O₂)-induced intracellular reactive oxygen species (ROS) production in HT-29 colorectal cells without exerting cytotoxicity. Additionally, lipopolysaccharide (LPS)-induced production of nitric oxide (a proinflammatory mediator as well as a reactive nitrogen species) was also inhibited by these fermented Miang extracts with an IC₅₀ values of 17.15 μg/mL (NFP), 20.17 μg/mL (FFP), 33.96 μg/mL (young tea leaves), and 31.33 μg/mL (mature tea leaves). Therefore, both NFP-Miang and FFP-Miang showed the potential to be targeted as natural bioactive functional ingredients with preventive properties against free radical and inflammatory-mediated diseases. Full article

(This article belongs to the Special Issue Antioxidants and Bioactive Compounds in Fermented Foods)

► Show Figures

Figure 1

17 pages, 1243 KiB

Open AccessReview

Metabolic Changes and Oxidative Stress in Diabetic Kidney Disease

by Midori Sakashita, Tetsuhiro Tanaka and Reiko Inagi

Antioxidants 2021, 10(7), 1143; https://doi.org/10.3390/antiox10071143 - 19 Jul 2021

Cited by 30 | Viewed by 3740

Abstract

Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease, and it is crucial to understand the pathophysiology of DKD. The control of blood glucose levels by various glucose-lowering drugs, the common use of inhibitors of the renin–angiotensin system, and the [...] Read more.

Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease, and it is crucial to understand the pathophysiology of DKD. The control of blood glucose levels by various glucose-lowering drugs, the common use of inhibitors of the renin–angiotensin system, and the aging of patients with diabetes can alter the disease course of DKD. Moreover, metabolic changes and associated atherosclerosis play a major role in the etiology of DKD. The pathophysiology of DKD is largely attributed to the disruption of various cellular stress responses due to metabolic changes, especially an increase in oxidative stress. Therefore, many antioxidants have been studied as therapeutic agents. Recently, it has been found that NRF2, a master regulator of oxidative stress, plays a major role in the pathogenesis of DKD and bardoxolone methyl, an activator of NRF2, has attracted attention as a drug that increases the estimated glomerular filtration rate in patients with DKD. This review outlines the altered stress responses of cellular organelles in DKD, their involvement in the pathogenesis of DKD, and discusses strategies for developing therapeutic agents, especially bardoxolone methyl. Full article

(This article belongs to the Special Issue Oxidative Stress in Kidney Disease)

► Show Figures

Figure 1

8 pages, 729 KiB

Open AccessArticle

Biocatalyzed Flow Oxidation of Tyrosol to Hydroxytyrosol and Efficient Production of Their Acetate Esters

by Francesca Annunziata, Martina L. Contente, Cecilia Pinna, Lucia Tamborini and Andrea Pinto

Antioxidants 2021, 10(7), 1142; https://doi.org/10.3390/antiox10071142 - 19 Jul 2021

Cited by 18 | Viewed by 3266

Abstract

Tyrosol (Ty) and hydroxytyrosol (HTy) are valuable dietary phenolic compounds present in olive oil and wine, widely used for food, nutraceutical and cosmetic applications. Ty and HTy are endowed with a number of health-related biological activities, including antioxidant, antimicrobial and anti-inflammatory properties. In [...] Read more.

Tyrosol (Ty) and hydroxytyrosol (HTy) are valuable dietary phenolic compounds present in olive oil and wine, widely used for food, nutraceutical and cosmetic applications. Ty and HTy are endowed with a number of health-related biological activities, including antioxidant, antimicrobial and anti-inflammatory properties. In this work, we developed a sustainable, biocatalyzed flow protocol for the chemo- and regio-selective oxidation of Ty into HTy catalyzed by free tyrosinase from Agaricus bisporus in a gas/liquid biphasic system. The aqueous flow stream was then in-line extracted to recirculate the water medium containing the biocatalyst and the excess ascorbic acid, thus improving the cost-efficiency of the process and creating a self-sufficient closed-loop system. The organic layer was purified in-line through a catch-and-release procedure using supported boronic acid that was able to trap HTy and leave the unreacted Ty in solution. Moreover, the acetate derivatives (TyAc and HTyAc) were produced by exploiting a bioreactor packed with an immobilized acyltransferase from Mycobacterium smegmatis (MsAcT), able to selectively act on the primary alcohol. Under optimized conditions, high-value HTy was obtained in 75% yield, whereas TyAc and HTyAc were isolated in yields of up to 80% in only 10 min of residence time. Full article

(This article belongs to the Special Issue Secondary Metabolites Extraction and/or Functionalization: from Industrial Co-product to Cosmetic Applications)

► Show Figures

Graphical abstract

23 pages, 2676 KiB

Open AccessArticle

UHPLC-HRMS Analysis of Fagus sylvatica (Fagaceae) Leaves: A Renewable Source of Antioxidant Polyphenols

by Marialuisa Formato, Simona Piccolella, Christian Zidorn and Severina Pacifico

Antioxidants 2021, 10(7), 1140; https://doi.org/10.3390/antiox10071140 - 19 Jul 2021

Cited by 16 | Viewed by 3130

Abstract

European beech (Fagus sylvatica L.) is a deciduous tree, widely distributed in Europe and largely appreciated for its wood and nutritive nuts. Beech leaf also enjoys food use as salad, but an understanding of its nutraceutical value is still far from being [...] Read more.

European beech (Fagus sylvatica L.) is a deciduous tree, widely distributed in Europe and largely appreciated for its wood and nutritive nuts. Beech leaf also enjoys food use as salad, but an understanding of its nutraceutical value is still far from being achieved. Indeed, and also taking into account beech leaf as a consistent biomass residue available beechwood production and use, it needs to be explored as a valuable renewable specialized source of bioactive molecules. In this context, an untargeted ultra-high-performance liquid chromatography hyphenated with high resolution mass spectrometry (UHPLC-HRMS) approach was favorably applied to a beech leaf alcoholic extract, which also was evaluated for its antiradical capability (by means of assays based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and [2,2’-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid)] (ABTS) radical cation) and its ferric ion reducing power. Redox mitochondrial activity towards Caco-2 cells paved the way to explore the extract’s capability to inhibit intracellular Reactive Oxygen Species (ROS) using 2’,7’dichlorofluorescin diacetate (DCFH-DA) assay. Hydroxycinnamoyl derivatives, mainly belonging to the chlorogenic acid class, and flavonoids were the main constituents. Uncommon flavanone C-glycosides were also found, together with a plentiful flavonol diversity. Cell-free and cell-based assays highlight its dose-dependent antioxidant efficacy, providing a foundation for further investigation of beech leaf constituents and its valorization and use as a reservoir of bioactive natural products with potential nutraceutical applications. Full article

(This article belongs to the Special Issue Antioxidant and Biological Properties of Plant Extracts)

► Show Figures

Graphical abstract

14 pages, 2480 KiB

Open AccessArticle

Dual Mechanisms of Cardiac Action Potential Prolongation by 4-Oxo-Nonenal Increasing the Risk of Arrhythmia; Late Na⁺ Current Induction and hERG K⁺ Channel Inhibition

by Seong-Woo Choi, Ming-Zhe Yin, Na-Kyeong Park, Joo-Han Woo and Sung-Joon Kim

Antioxidants 2021, 10(7), 1139; https://doi.org/10.3390/antiox10071139 - 19 Jul 2021

Viewed by 2095

Abstract

4-Oxo-nonenal (4-ONE) is an endogenous lipid peroxidation product that is more reactive than 4-hydroxy-nonenal (4-HNE). We previously reported the arrhythmic potential of 4-HNE by suppression of cardiac human Ether-a-go-go Related Gene (hERG) K⁺ channels with prolonged action potential duration (APD) in cardiomyocytes. [...] Read more.

4-Oxo-nonenal (4-ONE) is an endogenous lipid peroxidation product that is more reactive than 4-hydroxy-nonenal (4-HNE). We previously reported the arrhythmic potential of 4-HNE by suppression of cardiac human Ether-a-go-go Related Gene (hERG) K⁺ channels with prolonged action potential duration (APD) in cardiomyocytes. Here, we illustrate the higher arrhythmic risk of 4-ONE by modulating the cardiac hNa_V1.5 channel currents (I_NaV). Although the peak amplitude of I_NaV was not significantly changed by 4-ONE up to 10 μM, the rate of I_NaV inactivation was slowed, and the late Na⁺ current (I_NaL) became larger by 10 μM 4-ONE. The chemical modification of specific residues in hNa_V1.5 by 4-ONE was identified using MS-fingerprinting analysis. In addition to the changes in I_NaV, 4-ONE decreased the delayed rectifier K⁺ channel currents including the hERG current. The L-type Ca²⁺ channel current was decreased, whereas its inactivation was slowed by 4-ONE. The APD prolongation by 10 μM of 4-ONE was more prominent than that by 100 μM of 4-HNE. In the computational in silico cardiomyocyte simulation analysis, the changes of I_NaL by 4-ONE significantly exacerbated the risk of arrhythmia exhibited by the TdP marker, qNet. Our study suggests an arrhythmogenic effect of 4-ONE on cardiac ion channels, especially hNa_V1.5. Full article

(This article belongs to the Special Issue Role of Oxidative Stress and Antioxidants in Pathophysiology: A Commemorative Special Issue in Honour of Professor Mario Umberto Dianzani)

► Show Figures

Graphical abstract

15 pages, 2190 KiB

Open AccessReview

The Multifaceted Role of Flavonoids in Cancer Therapy: Leveraging Autophagy with a Double-Edged Sword

by Zhe Zhang, Jiayan Shi, Edouard C. Nice, Canhua Huang and Zheng Shi

Antioxidants 2021, 10(7), 1138; https://doi.org/10.3390/antiox10071138 - 19 Jul 2021

Cited by 30 | Viewed by 3917

Abstract

Flavonoids are considered as pleiotropic, safe, and readily obtainable molecules. A large number of recent studies have proposed that flavonoids have potential in the treatment of tumors by the modulation of autophagy. In many cases, flavonoids suppress cancer by stimulating excessive autophagy or [...] Read more.

Flavonoids are considered as pleiotropic, safe, and readily obtainable molecules. A large number of recent studies have proposed that flavonoids have potential in the treatment of tumors by the modulation of autophagy. In many cases, flavonoids suppress cancer by stimulating excessive autophagy or impairing autophagy flux especially in apoptosis-resistant cancer cells. However, the anti-cancer activity of flavonoids may be attenuated due to the simultaneous induction of protective autophagy. Notably, flavonoids-triggered protective autophagy is becoming a trend for preventing cancer in the clinical setting or for protecting patients from conventional therapeutic side effects in normal tissues. In this review, focusing on the underlying autophagic mechanisms of flavonoids, we hope to provide a new perspective for clinical application of flavonoids in cancer therapy. In addition, we highlight new research ideas for the development of new dosage forms of flavonoids to improve their various pharmacological effects, establishing flavonoids as ideal candidates for cancer prevention and therapy in the clinic. Full article

(This article belongs to the Special Issue Modulation of Autophagy by Dietary Polyphenols: Mechanisms and Health Benefits)

► Show Figures

Figure 1

17 pages, 2627 KiB

Open AccessArticle

DNA Damage in Human Amniotic Cells: Antigenotoxic Potential of Curcumin and α-Lipoic Acid

by Filomena Mottola, Marianna Santonastaso, Concetta Iovine, Cristina Rossetti, Valentina Ronga and Lucia Rocco

Antioxidants 2021, 10(7), 1137; https://doi.org/10.3390/antiox10071137 - 17 Jul 2021

Cited by 7 | Viewed by 2267

Abstract

Oxidative imbalances in the gestational phase are responsible for certain complications during pregnancy and for foetal and neonatal genetic disorders. In this work, using human amniocytes, we aimed to evaluate the protection provided to foetal DNA by two concentrations of antioxidant molecules, α-lipoic [...] Read more.

Oxidative imbalances in the gestational phase are responsible for certain complications during pregnancy and for foetal and neonatal genetic disorders. In this work, using human amniocytes, we aimed to evaluate the protection provided to foetal DNA by two concentrations of antioxidant molecules, α-lipoic acid (LA) and curcumin (Cur), against hydrogen peroxide (H₂O₂)-induced damage. Genotoxicity tests, performed by the random amplification of polymorphic DNA (RAPD-PCR) technique and TUNEL tests, showed that the lowest concentration of LA-protected cells and DNA from H₂O₂ insults. However, a greater ability to protect the amniocytes’ DNA against H₂O₂ was observed following co-treatment with the highest concentration of Cur with H₂O₂. In fact, a genomic template stability (GTS%) similar to that of the negative control and a statistically significant reduction in the DNA fragmentation index (DFI) were revealed. Moreover, following a combined treatment with both antioxidants and H₂O₂, no statistical difference from controls was observed, in terms of both induced mutations and DNA breaks. Furthermore, no effect on morphology or cell viability was observed. The results demonstrate the ability of LA and Cur to protect the genetic material of amniocytes against genotoxic insults, suggesting their beneficial effects in pathologies related to oxidative stress. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development)

► Show Figures

Figure 1

16 pages, 1393 KiB

Open AccessArticle

Comparison between In Vitro Chemical and Ex Vivo Biological Assays to Evaluate Antioxidant Capacity of Botanical Extracts

by Valentina Pasqualetti, Vittoria Locato, Chiara Fanali, Nadia Mulinacci, Sara Cimini, Anna Maria Morgia, Gabriella Pasqua and Laura De Gara

Antioxidants 2021, 10(7), 1136; https://doi.org/10.3390/antiox10071136 - 17 Jul 2021

Cited by 13 | Viewed by 2831

Abstract

The anti-oxidative activity of plant-derived extracts is well-known and confers health-promoting effects on functional foods and food supplements. Aim of this work is to evaluate the capability of two different assays to predict the real biological antioxidant efficiency. At this purpose, extracts from [...] Read more.

The anti-oxidative activity of plant-derived extracts is well-known and confers health-promoting effects on functional foods and food supplements. Aim of this work is to evaluate the capability of two different assays to predict the real biological antioxidant efficiency. At this purpose, extracts from five different plant-derived matrices and commercial purified phytochemicals were analyzed for their anti-oxidative properties by using well-standardized in vitro chemical method (TEAC) and an ex vivo biological assay. The biological assay, a cellular membrane system obtained from erythrocytes of healthy volunteers, is based on the capability of phytochemicals treatment to prevent membrane lipid peroxidation under oxidative stress by UV-B radiation. Plant extracts naturally rich in phenols with different structure and purified phytochemicals showed different in vitro and ex vivo antioxidant capacities. A high correlation between phenolic contents of the plant-derived extracts and their ability to prevent oxidative injuries in a biological system was found, thus underlying the relevance of this class of metabolites in preventing oxidative stress. On the other hand, a low correlation between the antioxidant capacities was shown between in vitro and ex vivo antioxidant assay. Moreover, data presented in this work show how food complex matrices are more effective in preventing oxidative damages at biological level than pure phytochemicals, even if for these latter, the antioxidant activity was generally higher than that observed for food complex matrices. Full article

(This article belongs to the Special Issue Plant Antioxidants in the “One Health” Paradigm)

► Show Figures

Graphical abstract

12 pages, 1554 KiB

Open AccessArticle

Hypoxia Tolerance Declines with Age in the Absence of Methionine Sulfoxide Reductase (MSR) in Drosophila melanogaster

by Nirthieca Suthakaran, Sanjana Chandran, Michael Iacobelli and David Binninger

Antioxidants 2021, 10(7), 1135; https://doi.org/10.3390/antiox10071135 - 17 Jul 2021

Cited by 1 | Viewed by 2274

Abstract

Unlike the mammalian brain, Drosophila melanogaster can tolerate several hours of hypoxia without any tissue injury by entering a protective coma known as spreading depression. However, when oxygen is reintroduced, there is an increased production of reactive oxygen species (ROS) that causes oxidative [...] Read more.

Unlike the mammalian brain, Drosophila melanogaster can tolerate several hours of hypoxia without any tissue injury by entering a protective coma known as spreading depression. However, when oxygen is reintroduced, there is an increased production of reactive oxygen species (ROS) that causes oxidative damage. Methionine sulfoxide reductase (MSR) acts to restore functionality to oxidized methionine residues. In the present study, we have characterized in vivo effects of MSR deficiency on hypoxia tolerance throughout the lifespan of Drosophila. Flies subjected to sudden hypoxia that lacked MSR activity exhibited a longer recovery time and a reduced ability to survive hypoxic/re-oxygenation stress as they approached senescence. However, when hypoxia was induced slowly, MSR deficient flies recovered significantly quicker throughout their entire adult lifespan. In addition, the wildtype and MSR deficient flies had nearly 100% survival rates throughout their lifespan. Neuroprotective signaling mediated by decreased apoptotic pathway activation, as well as gene reprogramming and metabolic downregulation are possible reasons for why MSR deficient flies have faster recovery time and a higher survival rate upon slow induction of spreading depression. Our data are the first to suggest important roles of MSR and longevity pathways in hypoxia tolerance exhibited by Drosophila. Full article

(This article belongs to the Special Issue Biological Significance of Methionine Oxidation and Reduction)

► Show Figures

Figure 1

26 pages, 5529 KiB

Open AccessArticle

The Interplay between S-Glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing Hearts

by Heidi Budde, Roua Hassoun, Melina Tangos, Saltanat Zhazykbayeva, Melissa Herwig, Marharyta Varatnitskaya, Marcel Sieme, Simin Delalat, Innas Sultana, Detmar Kolijn, Kamilla Gömöri, Muhammad Jarkas, Mária Lódi, Kornelia Jaquet, Árpád Kovács, Hans Georg Mannherz, Vasco Sequeira, Andreas Mügge, Lars I. Leichert, Samuel Sossalla and Nazha Hamdani Show full author list Hide full author list

Antioxidants 2021, 10(7), 1134; https://doi.org/10.3390/antiox10071134 - 16 Jul 2021

Cited by 14 | Viewed by 3050

Abstract

Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell [...] Read more.

Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell damage occurs, due to protein, DNA and lipid oxidation. Here, we investigated the oxidative modifications of myofilament proteins, and their role in modulating cardiomyocyte function in end-stage human failing hearts. We found altered maximum Ca²⁺-activated tension and Ca²⁺ sensitivity of force production of skinned single cardiomyocytes in end-stage human failing hearts compared to non-failing hearts, which was corrected upon treatment with reduced glutathione enzyme. This was accompanied by the increased oxidation of troponin I and myosin binding protein C, and decreased levels of protein kinases A (PKA)- and C (PKC)-mediated phosphorylation of both proteins. The Ca²⁺ sensitivity and maximal tension correlated strongly with the myofilament oxidation levels, hypo-phosphorylation, and oxidative stress parameters that were measured in all the samples. Furthermore, we detected elevated titin-based myocardial stiffness in HF myocytes, which was reversed by PKA and reduced glutathione enzyme treatment. Finally, many oxidative stress and inflammation parameters were significantly elevated in failing hearts compared to non-failing hearts, and corrected upon treatment with the anti-oxidant GSH enzyme. Here, we provide evidence that the altered mechanical properties of failing human cardiomyocytes are partially due to phosphorylation, S-glutathionylation, and the interplay between the two post-translational modifications, which contribute to the development of heart failure. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Diseases)

► Show Figures

Graphical abstract

12 pages, 4293 KiB

Open AccessArticle

Phenolic Extracts from Extra Virgin Olive Oils Inhibit Dipeptidyl Peptidase IV Activity: In Vitro, Cellular, and In Silico Molecular Modeling Investigations

by Carmen Lammi, Martina Bartolomei, Carlotta Bollati, Lorenzo Cecchi, Maria Bellumori, Emanuela Sabato, Vistoli Giulio, Nadia Mulinacci and Anna Arnoldi

Antioxidants 2021, 10(7), 1133; https://doi.org/10.3390/antiox10071133 - 16 Jul 2021

Cited by 8 | Viewed by 2448

Abstract

Two extra virgin olive oil (EVOO) phenolic extracts (BUO and OMN) modulate DPP-IV activity. The in vitro DPP-IV activity assay was performed at the concentrations of 1, 10, 100, 500, and 1000 μg/mL, showing a dose-dependent inhibition by 6.8 ± 1.9, 17.4 ± [...] Read more.

Two extra virgin olive oil (EVOO) phenolic extracts (BUO and OMN) modulate DPP-IV activity. The in vitro DPP-IV activity assay was performed at the concentrations of 1, 10, 100, 500, and 1000 μg/mL, showing a dose-dependent inhibition by 6.8 ± 1.9, 17.4 ± 6.1, 37.9 ± 2.4, 57.8 ± 2.9, and 81 ± 1.4% for BUO and by 5.4 ± 1.7, 8.9 ± 0.4, 28.4 ± 7.2, 52 ± 1.3, and 77.5 ± 3.5% for OMN. Moreover, both BUO and OMN reduced the DPP-IV activity expressed by Caco-2 cells by 2.9 ± 0.7, 44.4 ± 0.7, 61.2 ± 1.8, and 85 ± 4.2% and by 3 ± 1.9, 35 ± 9.4, 60 ± 7.2, and 82 ± 2.8%, respectively, at the same doses. The concentration of the most abundant and representative secoiridoids within both extracts was analyzed by nuclear magnetic resonance (¹H-NMR). Oleuropein, oleacein, oleocanthal, hydroxytyrosol, and tyrosol, tested alone, reduced the DPP-IV activity, with IC₅₀ of 472.3 ± 21.7, 187 ± 11.4, 354.5 ± 12.7, 741.6 ± 35.7, and 1112 ± 55.6 µM, respectively. Finally, in silico molecular docking simulations permitted the study of the binding mode of these compounds. Full article

(This article belongs to the Special Issue Olive Oil Antioxidants)

► Show Figures

Figure 1

14 pages, 2823 KiB

Open AccessArticle

A Machine Learning Algorithm for Quantitatively Diagnosing Oxidative Stress Risks in Healthy Adult Individuals Based on Health Space Methodology: A Proof-of-Concept Study Using Korean Cross-Sectional Cohort Data

by Youjin Kim, Yunsoo Kim, Jiyoung Hwang, Tim J. van den Broek, Bumjo Oh, Ji Yeon Kim, Suzan Wopereis, Jildau Bouwman and Oran Kwon

Antioxidants 2021, 10(7), 1132; https://doi.org/10.3390/antiox10071132 - 16 Jul 2021

Cited by 2 | Viewed by 3729

Abstract

Oxidative stress aggravates the progression of lifestyle-related chronic diseases. However, knowledge and practices that enable quantifying oxidative stress are still lacking. Here, we performed a proof-of-concept study to predict the oxidative stress status in a healthy population using retrospective cohort data from Boramae [...] Read more.

Oxidative stress aggravates the progression of lifestyle-related chronic diseases. However, knowledge and practices that enable quantifying oxidative stress are still lacking. Here, we performed a proof-of-concept study to predict the oxidative stress status in a healthy population using retrospective cohort data from Boramae medical center in Korea (n = 1328). To obtain binary performance measures, we selected healthy controls versus oxidative disease cases based on the “health space” statistical methodology. We then developed a machine learning algorithm for discrimination of oxidative stress status using least absolute shrinkage and selection operator (LASSO)/elastic net regression with 10-fold cross-validation. A proposed fine-tune model included 16 features out of the full spectrum of diverse and complex data. The predictive performance was externally evaluated by generating receiver operating characteristic curves with area under the curve of 0.949 (CI 0.925 to 0.974), sensitivity of 0.923 (CI 0.879 to 0.967), and specificity of 0.855 (CI 0.795 to 0.915). Moreover, the discrimination power was confirmed by applying the proposed diagnostic model to the full dataset consisting of subjects with various degrees of oxidative stress. The results provide a feasible approach for stratifying the oxidative stress risks in the healthy population and selecting appropriate strategies for individual subjects toward implementing data-driven precision nutrition. Full article

(This article belongs to the Special Issue Oxidative Stress in Human Diseases: Focus on Redox Status Assessment in Biological Fluids, Tissues and Cells)

► Show Figures

Graphical abstract

11 pages, 266 KiB

Open AccessArticle

Sperm Motility, Oxidative Status, and Mitochondrial Activity: Exploring Correlation in Different Species

by Alessandra Gallo, Maria Consiglia Esposito, Elisabetta Tosti and Raffaele Boni

Antioxidants 2021, 10(7), 1131; https://doi.org/10.3390/antiox10071131 - 16 Jul 2021

Cited by 31 | Viewed by 3173

Abstract

Sperm quality assessment is the first step for evaluating male fertility and includes the estimation of sperm concentration, motility, and morphology. Nevertheless, other parameters can be assessed providing additional information on the male reproductive potential. This study aimed to evaluate and correlate the [...] Read more.

Sperm quality assessment is the first step for evaluating male fertility and includes the estimation of sperm concentration, motility, and morphology. Nevertheless, other parameters can be assessed providing additional information on the male reproductive potential. This study aimed to evaluate and correlate the oxidative status, mitochondrial functionality, and motility in spermatozoa of two marine invertebrate (Ciona robusta and Mytilus galloprovincialis) and one mammalian (Bos taurus) species. By combining fluorescent staining and spectrofluorometer, sperm oxidative status was evaluated through intracellular reactive oxygen species (ROS) and plasma membrane lipid peroxidation (LPO) analysis. Mitochondrial functionality was assessed through the mitochondrial membrane potential (MMP). In the three examined species, a negative correlation emerged between sperm motility vs ROS levels and LPO. Sperm motility positively correlated with MMP in bovine, whereas these parameters were not related in ascidian or even negatively related in mussel spermatozoa. MMP was negatively related to ROS and LPO levels in ascidians, only to LPO in bovine, and positively related in mussel spermatozoa. These results suggest that energy sources for sperm motility vary between species and that ROS causes a decline in sperm motility via oxidative damage of membrane lipids. Overall, this study validates the use of fluorescent probes in combination with spectrofluorometer as a simple and powerful methodology for supplementary evaluation of sperm quality shedding light on new potential quality markers and provided relevant information on sperm energetic metabolism. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development)

► Show Figures

Graphical abstract

18 pages, 1074 KiB

Open AccessArticle

Encapsulation of Phenolic Compounds from a Grape Cane Pilot-Plant Extract in Hydroxypropyl Beta-Cyclodextrin and Maltodextrin by Spray Drying

by Danilo Escobar-Avello, Javier Avendaño-Godoy, Jorge Santos, Julián Lozano-Castellón, Claudia Mardones, Dietrich von Baer, Javiana Luengo, Rosa M. Lamuela-Raventós, Anna Vallverdú-Queralt and Carolina Gómez-Gaete

Antioxidants 2021, 10(7), 1130; https://doi.org/10.3390/antiox10071130 - 15 Jul 2021

Cited by 29 | Viewed by 5827

Abstract

Grape canes, the main byproducts of the viticulture industry, contain high-value bioactive phenolic compounds, whose application is limited by their instability and poorly solubility in water. Encapsulation in cyclodextrins allows these drawbacks to be overcome. In this work, a grape cane pilot-plant extract [...] Read more.

Grape canes, the main byproducts of the viticulture industry, contain high-value bioactive phenolic compounds, whose application is limited by their instability and poorly solubility in water. Encapsulation in cyclodextrins allows these drawbacks to be overcome. In this work, a grape cane pilot-plant extract (GC_PPE) was encapsulated in hydroxypropyl beta-cyclodextrin (HP-β-CD) by a spray-drying technique and the formation of an inclusion complex was confirmed by microscopy and infrared spectroscopy. The phenolic profile of the complex was analyzed by LC-ESI-LTQ-Orbitrap-MS and the encapsulation efficiency of the phenolic compounds was determined. A total of 42 compounds were identified, including stilbenes, flavonoids, and phenolic acids, and a complex of (epi)catechin with β-CD was detected, confirming the interaction between polyphenols and cyclodextrin. The encapsulation efficiency for the total extract was 80.5 ± 1.1%, with restrytisol showing the highest value (97.0 ± 0.6%) and (E)-resveratrol (32.7 ± 2.8%) the lowest value. The antioxidant capacity of the inclusion complex, determined by ORAC-FL, was 5300 ± 472 µmol TE/g DW, which was similar to the value obtained for the unencapsulated extract. This formulation might be used to improve the stability, solubility, and bioavailability of phenolic compounds of the GC_PPE for water-soluble food and pharmaceutical applications. Full article

(This article belongs to the Special Issue Characterization and Encapsulation of Natural Antioxidants: Interaction, Protection and Delivery)

► Show Figures

Figure 1

22 pages, 3488 KiB

Open AccessReview

Arbutin as a Skin Depigmenting Agent with Antimelanogenic and Antioxidant Properties

by Yong Chool Boo

Antioxidants 2021, 10(7), 1129; https://doi.org/10.3390/antiox10071129 - 15 Jul 2021

Cited by 66 | Viewed by 12415

Abstract

Arbutin is a compound of hydroquinone and D-glucose, and it has been over 30 years since there have been serious studies on the skin lightening action of this substance. In the meantime, there have been debates and validation studies about the mechanism of [...] Read more.

Arbutin is a compound of hydroquinone and D-glucose, and it has been over 30 years since there have been serious studies on the skin lightening action of this substance. In the meantime, there have been debates and validation studies about the mechanism of action of this substance as well as its skin lightening efficacy and safety. Several analogs or derivatives of arbutin have been developed and studied for their melanin synthesis inhibitory action. Formulations have been developed to improve the stability, transdermal delivery, and release of arbutin, and device usage to promote skin absorption has been developed. Substances that inhibit melanin synthesis synergistically with arbutin have been explored. The skin lightening efficacy of arbutin alone or in combination with other active ingredients has been clinically evaluated. Combined therapy with arbutin and laser could give enhanced depigmenting efficacy. The use of arbutin causes dermatitis rarely, and caution is recommended for the use of arbutin-containing products, especially from the viewpoint that hydroquinone may be generated during product use. Studies on the antioxidant properties of arbutin are emerging, and these antioxidant properties are proposed to contribute to the skin depigmenting action of arbutin. It is hoped that this review will help to understand the pros and cons of arbutin as a cosmetic ingredient, and will lead to future research directions for developing advanced skin lightening and protecting cosmetic products. Full article

(This article belongs to the Special Issue The Potential of Dietary Antioxidants)

► Show Figures

Figure 1

28 pages, 2740 KiB

Open AccessArticle

GSNOR Contributes to Demethylation and Expression of Transposable Elements and Stress-Responsive Genes

by Eva Esther Rudolf, Patrick Hüther, Ignasi Forné, Elisabeth Georgii, Yongtao Han, Rüdiger Hell, Markus Wirtz, Axel Imhof, Claude Becker, Jörg Durner and Christian Lindermayr

Antioxidants 2021, 10(7), 1128; https://doi.org/10.3390/antiox10071128 - 15 Jul 2021

Cited by 10 | Viewed by 3266

Abstract

In the past, reactive nitrogen species (RNS) were supposed to be stress-induced by-products of disturbed metabolism that cause oxidative damage to biomolecules. However, emerging evidence demonstrates a substantial role of RNS as endogenous signals in eukaryotes. In plants, S-nitrosoglutathione (GSNO) is the dominant [...] Read more.

In the past, reactive nitrogen species (RNS) were supposed to be stress-induced by-products of disturbed metabolism that cause oxidative damage to biomolecules. However, emerging evidence demonstrates a substantial role of RNS as endogenous signals in eukaryotes. In plants, S-nitrosoglutathione (GSNO) is the dominant RNS and serves as the ^•NO donor for S-nitrosation of diverse effector proteins. Remarkably, the endogenous GSNO level is tightly controlled by S-nitrosoglutathione reductase (GSNOR) that irreversibly inactivates the glutathione-bound NO to ammonium. Exogenous feeding of diverse RNS, including GSNO, affected chromatin accessibility and transcription of stress-related genes, but the triggering function of RNS on these regulatory processes remained elusive. Here, we show that GSNO reductase-deficient plants (gsnor1-3) accumulate S-adenosylmethionine (SAM), the principal methyl donor for methylation of DNA and histones. This SAM accumulation triggered a substantial increase in the methylation index (MI = [SAM]/[S-adenosylhomocysteine]), indicating the transmethylation activity and histone methylation status in higher eukaryotes. Indeed, a mass spectrometry-based global histone profiling approach demonstrated a significant global increase in H3K9me2, which was independently verified by immunological detection using a selective antibody. Since H3K9me2-modified regions tightly correlate with methylated DNA regions, we also determined the DNA methylation status of gsnor1-3 plants by whole-genome bisulfite sequencing. DNA methylation in the CG, CHG, and CHH contexts in gsnor1-3 was significantly enhanced compared to the wild type. We propose that GSNOR1 activity affects chromatin accessibility by controlling the transmethylation activity (MI) required for maintaining DNA methylation and the level of the repressive chromatin mark H3K9me2. Full article

(This article belongs to the Special Issue Redox in Plants)

► Show Figures

Figure 1

16 pages, 2977 KiB

Open AccessArticle

Hydroxytyrosol Selectively Affects Non-Enzymatic Glycation in Human Insulin and Protects by AGEs Cytotoxicity

by Ivana Sirangelo, Margherita Borriello, Maria Liccardo, Marika Scafuro, Paola Russo and Clara Iannuzzi

Antioxidants 2021, 10(7), 1127; https://doi.org/10.3390/antiox10071127 - 15 Jul 2021

Cited by 15 | Viewed by 2303

Abstract

Hydroxytyrosol (HT), the major phenolic compound in olive oil, is attracting increasing interest for its beneficial properties including a notable antioxidant and anti-inflammatory power. In this study, using a combination of biophysical and cell biology techniques, we have tested the role of HT [...] Read more.

Hydroxytyrosol (HT), the major phenolic compound in olive oil, is attracting increasing interest for its beneficial properties including a notable antioxidant and anti-inflammatory power. In this study, using a combination of biophysical and cell biology techniques, we have tested the role of HT in the formation of advanced glycation end-products (AGEs). AGEs have a key role in clinical sciences as they have been associated to diabetes, neurodegenerative and cardiovascular diseases. In addition, as the incidence of Alzheimer’s disease (AD) is strongly increased in diabetic patients, AGE formation is supposed to be involved in the development of the pathological hallmarks of AD. Our data show that HT selectively inhibits protein glycation reaction in human insulin, and it is able to counteract the AGE-induced cytotoxicity in human neurotypical cells by acting on SIRT1 level and oxidative stress, as well as on inflammatory response. This study identifies new beneficial properties for HT and suggests it might be a promising molecule in protecting against the AGE-induced toxicity, a key mechanism underlying the development and progression of neurodegenerative disorders. Full article

(This article belongs to the Special Issue Natural or Synthetic Antioxidants for Neurodegenerative Diseases and Brain Health)

► Show Figures

Figure 1

14 pages, 1128 KiB

Open AccessArticle

Time Course of Redox Biomarkers in COVID-19 Pneumonia: Relation with Inflammatory, Multiorgan Impairment Biomarkers and CT Findings

by Tijana Kosanovic, Dragan Sagic, Vladimir Djukic, Marija Pljesa-Ercegovac, Ana Savic-Radojevic, Zoran Bukumiric, Miodrag Lalosevic, Marjana Djordjevic, Vesna Coric and Tatjana Simic

Antioxidants 2021, 10(7), 1126; https://doi.org/10.3390/antiox10071126 - 14 Jul 2021

Cited by 15 | Viewed by 3515

Abstract

Although the original data on systemic oxidative stress in COVID-19 patients have recently started to emerge, we are still far from a complete profile of changes in patients’ redox homeostasis. We aimed to assess the extent of oxidative damage of proteins, lipids and [...] Read more.

Although the original data on systemic oxidative stress in COVID-19 patients have recently started to emerge, we are still far from a complete profile of changes in patients’ redox homeostasis. We aimed to assess the extent of oxidative damage of proteins, lipids and DNA during the course of acute disease, as well as their association with CT pulmonary patterns. In order to obtain more insight into the origin of the systemic oxidative stress, the observed parameters were correlated with inflammatory biomarkers and biomarkers of multiorgan impairment. In this prospective study, we included 58 patients admitted between July and October 2020 with COVID-19 pneumonia. Significant changes in malondialdehyde, 8-hydroxy-2’-deoxyguanosine and advanced oxidation protein products levels exist during the course of COVID-19. Special emphasis should be placed on the fact that the pattern of changes differs between non-hospitalized and hospitalized individuals. Our results point to the time-dependent relation of oxidative stress parameters with inflammatory and multiorgan impairment biomarkers, as well as pulmonary patterns in COVID-19 pneumonia patients. Correlation between redox biomarkers and immunological or multiorgan impairment biomarkers, as well as pulmonary CT pattern, confirms the suggested involvement of neutrophils networks, IL-6 production, along with different organ/tissue involvement in systemic oxidative stress in COVID-19. Full article

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Antioxidants, Volume 10, Issue 7 (July 2021) – 164 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI