Special Issue "Modulation of Reactive Oxygen Species in Health and Disease"

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 August 2019).

Special Issue Editor

Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS) include radical (e.g., superoxide anion and hydroxyl radical) and non-radical (e.g., hydrogen peroxide and hypochlorous acid) oxygen-derived species that regulate numerous physiological processes. Generated by various cellular mechanisms including the mitochondrial electron transport system and enzymes (e.g., NADPH oxidases and xanthine oxidase), ROS play vital roles in signal transduction mechanisms and in the regulation of cellular processes, ranging from cell viability/proliferation to cell death. Not surprisingly, high levels of ROS in biological systems, resulting from either their excessive production and/or a weak antioxidant defences, could lead to the development of pathological conditions, such as diabetes, obesity, and chronic inflammatory, cardiovascular and neurodegenerative diseases. While lower, but sustained, levels of ROS may promote carcinogenesis, for example, excessive levels could make tumour cells susceptible (e.g., to chemotherapeutic agents) to cell death. Hence, there is a growing awareness that ROS modulation through various pharmacological and other approaches could be employed to alter normal cellular physiology and/or pathologies. This Special Issue is dedicated to providing more insight into recent developments in the field. We welcome original and review article contributions on mechanisms of ROS modulation in health and disease. Novel therapeutic intervention approaches targeting ROS formation or elimination are also welcome.

Prof. Solomon Habtemariam
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Reactive oxygen species
  • Hydroxyl radical
  • Hydrogen peroxide
  • Free radicals
  • Antioxidants

Published Papers (8 papers)

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Editorial

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Open AccessEditorial
Modulation of Reactive Oxygen Species in Health and Disease
Antioxidants 2019, 8(11), 513; https://doi.org/10.3390/antiox8110513 - 26 Oct 2019
Cited by 2
Abstract
In diverse living organisms, signaling within the cell, chemical communication between cells or simply the fate of cells to survive or die is largely dependent on the intricate balance of control mechanisms related to reactive oxygen species (ROS)[...] Full article
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
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Research

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Open AccessArticle
Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis
Antioxidants 2019, 8(10), 441; https://doi.org/10.3390/antiox8100441 - 01 Oct 2019
Cited by 4
Abstract
The immunological response in bacterial meningitis (BM) causes the formation of reactive oxygen and nitrogen species (ROS, RNS) and activates myeloperoxidase (MPO), an inflammatory enzyme. Thus, structural oxidative and nitrosative damage to proteins and DNA occurs. We aimed to asses these events in [...] Read more.
The immunological response in bacterial meningitis (BM) causes the formation of reactive oxygen and nitrogen species (ROS, RNS) and activates myeloperoxidase (MPO), an inflammatory enzyme. Thus, structural oxidative and nitrosative damage to proteins and DNA occurs. We aimed to asses these events in the cerebrospinal fluid (CSF) of pediatric BM patients. Phenylalanine (Phe), para-tyrosine (p-Tyr), nucleoside 2′-deoxiguanosine (2dG), and biomarkers of ROS/RNS-induced protein and DNA oxidation: ortho-tyrosine (o-Tyr), 3-chlorotyrosine (3Cl-Tyr), 3-nitrotyrosine (3NO₂-Tyr) and 8-oxo-2′-deoxyguanosine (8OHdG), concentrations were measured by liquid chromatography coupled to tandem mass spectrometry in the initial CSF of 79 children with BM and 10 without BM. All biomarkers, normalized with their corresponding precursors, showed higher median concentrations (p < 0.0001) in BM compared with controls, except 8OHdG/2dG. The ratios o-Tyr/Phe, 3Cl-Tyr/p-Tyr and 3NO₂-Tyr/p-Tyr were 570, 20 and 4.5 times as high, respectively. A significantly higher 3Cl-Tyr/p-Tyr ratio was found in BM caused by Streptococcus pneumoniae, than by Haemophilus influenzae type b, or Neisseria meningitidis (p = 0.002 for both). In conclusion, biomarkers indicating oxidative damage to proteins distinguished BM patients from non-BM, most clearly the o-Tyr/Phe ratio. The high 3Cl-Tyr/p-Tyr ratio in pneumococcal meningitis suggests robust inflammation because 3Cl-Tyr is a marker of MPO activation and, indirectly, of inflammation. Full article
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
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Open AccessArticle
Glutathione Induced Immune-Stimulatory Activity by Promoting M1-Like Macrophages Polarization via Potential ROS Scavenging Capacity
Antioxidants 2019, 8(9), 413; https://doi.org/10.3390/antiox8090413 - 18 Sep 2019
Cited by 4
Abstract
The present study investigated the immunomodulatory activity of reduced glutathione (GSH) by assessment of the macrophage polarization (MP)-mediated immune response in RAW 264.7 cells. Furthermore, we identified the signal pathway associated with immune regulation by GSH. The expressions of MP-associated cytokines and chemokines [...] Read more.
The present study investigated the immunomodulatory activity of reduced glutathione (GSH) by assessment of the macrophage polarization (MP)-mediated immune response in RAW 264.7 cells. Furthermore, we identified the signal pathway associated with immune regulation by GSH. The expressions of MP-associated cytokines and chemokines were assessed using cytokine array, nCounter Sprit platform, ELISA and immunoblotting. Phagocytosis activity and intracellular reactive oxygen species (ROS) generation were measured using fluorescence-activated cell sorter. As results of the cytokine array and nCounter gene array, GSH not only up-regulated pro-inflammatory cytokines, including interleukins and tumor necrosis factor-α, but also overexpressed neutrophil-attracting chemokines. Furthermore, GSH significantly stimulated the production of immune mediators, including nitric oxide and PGE2, as well as phagocytosis activity through nuclear factor kappa B activation. In addition, GSH significantly decreased LPS-induced ROS generation, which was associated with an activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2)/ heme oxygenease-1 (HO-1) signaling pathway. Our results suggest that GSH has potential ROS scavenging capacity via the induction of Nrf2-mediated HO-1, and immune-enhancing activity by regulation of M1-like macrophage polarization, indicating that GSH may be a useful strategy to increase the human defense system. Full article
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
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Open AccessArticle
Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment
Antioxidants 2019, 8(9), 338; https://doi.org/10.3390/antiox8090338 - 23 Aug 2019
Cited by 4
Abstract
Unexplained infertility occurs when common causes for a couple’s inability to conceive have been excluded. Although origins of idiopathic infertility are still unclear, factors, such as an altered oxidative balance, are believed to be involved. Melatonin is an outstanding antioxidant reportedly present in [...] Read more.
Unexplained infertility occurs when common causes for a couple’s inability to conceive have been excluded. Although origins of idiopathic infertility are still unclear, factors, such as an altered oxidative balance, are believed to be involved. Melatonin is an outstanding antioxidant reportedly present in the follicular fluid (FF), which has been suggested as a useful tool in the management of human fertility. Herein, we observed that intrafollicular concentrations of melatonin were blunted in women with unexplained infertility (UI), which was associated with a marked oxidative imbalance in UI patients’ FF. Based on these findings, this randomized pilot study was aimed at assessing whether exogenous melatonin ameliorated oxidative stress and improved in vitro fertilization (IVF) success rates in UI. Thus, 3 mg/day or 6 mg/day of melatonin were given to UI patients for a period spanning from the first appointment to control ovarian stimulation until the day of follicular puncture. Our results indicate that melatonin supplementation, irrespective of the two doses tested, ameliorated intrafollicular oxidative balance and oocyte quality in UI patients, and that this translated into a slight increase in the rate of pregnancies/live births. Therefore, although the indoleamine has shown therapeutic potential in this clinical setting, larger clinical trials in populations with different backgrounds are encouraged to corroborate the usefulness of melatonin. Full article
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
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Open AccessArticle
Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for glutaredoxin-2
Antioxidants 2019, 8(8), 245; https://doi.org/10.3390/antiox8080245 - 26 Jul 2019
Cited by 3
Abstract
Our group recently published a study demonstrating that deleting the gene encoding the matrix thiol oxidoreductase, glutaredoxin-2 (GRX2), alters the bioenergetics of mitochondria isolated from male C57BL/6N mice. Here, we conducted a similar study, examining H2O2 production and respiration in [...] Read more.
Our group recently published a study demonstrating that deleting the gene encoding the matrix thiol oxidoreductase, glutaredoxin-2 (GRX2), alters the bioenergetics of mitochondria isolated from male C57BL/6N mice. Here, we conducted a similar study, examining H2O2 production and respiration in mitochondria isolated from female mice heterozygous (GRX2+/−) or homozygous (GRX2−/−) for glutaredoxin-2. First, we observed that deleting the Grx2 gene does not alter the rate of H2O2 production in liver and muscle mitochondria oxidizing pyruvate, α-ketoglutarate, or succinate. Examination of the rates of H2O2 release from liver mitochondria isolated from male and female mice revealed that (1) sex has an impact on the rate of ROS production by liver and muscle mitochondria and (2) loss of GRX2 only altered ROS release in mitochondria collected from male mice. Assessment of the bioenergetics of these mitochondria revealed that loss of GRX2 increased proton leak-dependent and phosphorylating respiration in liver mitochondria isolated from female mice but did not alter rates of respiration in liver mitochondria from male mice. Furthermore, we found that deleting the Grx2 gene did not alter rates of respiration in muscle mitochondria collected from female mice. This contrasts with male mice where loss of GRX2 substantially augmented proton leaks and ADP-stimulated respiration. Our findings indicate that some fundamental sexual dimorphisms exist between GRX2-deficient male and female rodents. Full article
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
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Open AccessArticle
Antioxidant and Rutin Content Analysis of Leaves of the Common Buckwheat (Fagopyrum esculentum Moench) Grown in the United Kingdom: A Case Study
Antioxidants 2019, 8(6), 160; https://doi.org/10.3390/antiox8060160 - 03 Jun 2019
Cited by 3
Abstract
The common buckwheat, Fagopyrum esculentum Moench (Polygonaceae) is a gluten-free pseudocereal that has been gaining in popularity in recent years as a low-calorie and nutrient-rich healthy food option. Buckwheat farming is common in Eastern European countries and the Far East, while in the [...] Read more.
The common buckwheat, Fagopyrum esculentum Moench (Polygonaceae) is a gluten-free pseudocereal that has been gaining in popularity in recent years as a low-calorie and nutrient-rich healthy food option. Buckwheat farming is common in Eastern European countries and the Far East, while in the UK and other Western European countries, the plant has limited medicinal or food applications. The vegetative parts, particularly the leaves and flowers, are among the best-known sources of the bioactive compound, rutin. Hence, functional foods originated from buckwheat leaves are common, although the scope of such applications is limited by phototoxicity associated with the fagopyrin composition. Here, the antioxidant and rutin composition of the leaves of the plant grown in the UK are assessed. The methanol extract of the leaves displayed a potent DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging effect along with reducing power. Quantitative High Performance Liquid Chromatography (HPLC)-based analysis showed the rutin content of the leaves as 3417 mg/100g (on dry weight (DW) basis). The identity of rutin was also confirmed by isolation and structural elucidation based on spectroscopic studies. From the chemical content analysis, including fagopyrin levels and the antioxidant assays, UK-grown buckwheat has potential as a commercial source of rutin or as a functional food. Full article
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
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Open AccessArticle
Expression of Antioxidant Enzymes in Patients with Uterine Polyp, Myoma, Hyperplasia, and Adenocarcinoma
Antioxidants 2019, 8(4), 97; https://doi.org/10.3390/antiox8040097 - 11 Apr 2019
Cited by 2
Abstract
We previously found that compared to patients with benign uterine diseases (polyps, myomas), patients with premalignant (hyperplasia simplex and complex) and malignant (adenocarcinoma) lesions had enhanced lipid peroxidation and altered uterine antioxidant enzyme (AOE) activities. To further elucidate the mechanism of the observed [...] Read more.
We previously found that compared to patients with benign uterine diseases (polyps, myomas), patients with premalignant (hyperplasia simplex and complex) and malignant (adenocarcinoma) lesions had enhanced lipid peroxidation and altered uterine antioxidant enzyme (AOE) activities. To further elucidate the mechanism of the observed changes, we examined protein and mRNA levels of copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and transcription factor Nrf2. We also examined correlations of AOE expression with AOE activity, lipid hydroperoxides (LOOH) level, and level of Nrf2. Our results showed decreased CuZnSOD, CAT, and Nrf2 levels, and increased GPx and GR levels in hyperplasias, while in patients with adenocarcinoma, the level of CAT was decreased and GR was increased, compared to benign groups. Similar changes in mRNA levels were also detected, indicating predominantly translational control of the AOE expression. The positive correlation of enzyme expression/activity was recorded for CuZnSOD, GPx, and GR, but only among groups with benign diseases. Only GR and GPx expressions were positively correlated with LOOH. Nrf2 protein was positively correlated with mRNA levels of CuZnSOD and GR. Observed results indicate involvement of diverse redox mechanisms in etiopathogenesis of different gynecological diseases, and may improve redox-based approaches in current clinical practice. Full article
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
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Review

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Open AccessReview
A Review of Oxidative Stress and Urinary Dysfunction Caused by Bladder Outlet Obstruction and Treatments Using Antioxidants
Antioxidants 2019, 8(5), 132; https://doi.org/10.3390/antiox8050132 - 15 May 2019
Cited by 3
Abstract
Urinary dysfunction is a common pathological condition that can significantly decrease the quality of life. Bladder outlet obstruction (BOO) is a major cause of urinary dysfunction, and various lower urinary tract diseases including benign prostatic hyperplasia and urethral stricture disease cause BOO. According [...] Read more.
Urinary dysfunction is a common pathological condition that can significantly decrease the quality of life. Bladder outlet obstruction (BOO) is a major cause of urinary dysfunction, and various lower urinary tract diseases including benign prostatic hyperplasia and urethral stricture disease cause BOO. According to the results of a variety of animal experiments on partial BOO (PBOO), there is a general agreement that ischemic conditions and repeated ischemia/reperfusion of the bladder are closely associated with BOO-induced bladder damage, and that increased oxidative stress by ischemia/reperfusion plays a crucial role in the pathological mechanisms underlying urinary dysfunction. Changes in biomarkers of oxidative stress in PBOO animal models support this association between oxidative stress and urinary dysfunction. Oxidative stress is defined as an imbalance between the production of pro-oxidants, such as free radicals and reactive species, and their elimination through protective mechanisms of antioxidants. Therefore, organizing the knowledge on the state of oxidative stress, changes in biomarkers, and biological roles of antioxidants in systemic and bladder tissues is essential to understand the detailed pathological characteristics of the urinary dysfunction caused by PBOO. Furthermore, information on drugs and supplements that have antioxidant effects is important for defining treatment strategies for urinary dysfunction with PBOO. In this review, we paid special attention to the following three issues; (1) changes in oxidative stress, including its biomarkers, (2) antioxidant status, and (3) previous reports on treatment strategies involving agents with antioxidative activity for urinary dysfunction caused by BOO. In particular, we provide systematic information on the detailed mechanisms underlying the antioxidative effects of agents used to treat PBOO. In addition, we show present research issues and research limitations, as well as suggest possible future antioxidant treatment strategies for patients with PBOO. Full article
(This article belongs to the Special Issue Modulation of Reactive Oxygen Species in Health and Disease)
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