Oxidative Stress in Human Diseases: Focus on Redox Status Assessment in Biological Fluids, Tissues and Cells

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 (30 April 2021) | Viewed by 24611

Special Issue Editors


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Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, Viale Morgagni 50, 50134 Florence, Italy
Interests: redox markers; antioxidant capacity; post-translational oxidative modification; ROS sources
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Guest Editor
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Firenze, 50121 Firenze, Italy
Interests: thrombosis; fibrinogen; oxidative stress; protein structure
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Reactive oxygen species are involved in a multitude of physiological mechanisms. However, despite the development of a complex antioxidant system, their excessive level, which is responsible for the onset of oxidative stress, may contribute to the initiation and progression of tissue/organ injury. The assessment of redox status in tissues/organs and body fluids remains an open challenge due to a lack of validated oxidative stress biomarkers. Indeed, a very large number of molecules with different reactivities exist and the evaluation of a single redox marker gives limited information.

The World Health Organization has defined a biomarker as any substance, structure, or process that can be measured in a biological sample and influence or predict the incidence of outcome or disease. Oxidative stress markers can be measured and there is evidence that suggests that oxidative stress can influence the disease, but a clinically relevant biomarker must possess some important additional issues. In particular, a clinically useful biomarker should be diagnostic, prognostic, or correlate with disease activity and should be stable, cost-effective, and present in easy obtainable biological samples. These requirements are not easily fulfilled by current markers. For this reason, analytical issues regarding the validation of oxidative stress biomarkers have recently received substantial attention due to the increasing interest in investigating their potential clinical applications.

On these bases, we invite you to submit your latest research findings or review articles to this Special Issue, which is focused on the assessment of redox status in physiologic and pathologic human conditions. Both in vitro and in vivo studies relating to these topics will be suitable for the current issue. We look forward to your contribution.

Dr. Claudia Fiorillo
Dr. Matteo Becatti
Guest Editors

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Keywords

  • Oxidative stress markers
  • Antioxidants
  • Human diseases

Published Papers (7 papers)

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Research

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14 pages, 2823 KiB  
Article
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 3711
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
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19 pages, 1459 KiB  
Article
Clinical and Molecular-Genetic Insights into the Role of Oxidative Stress in Diabetic Retinopathy: Antioxidant Strategies and Future Avenues
by Silvia M. Sanz-González, José J. García-Medina, Vicente Zanón-Moreno, María I. López-Gálvez, David Galarreta-Mira, Lilianne Duarte, Mar Valero-Velló, Ana I. Ramírez, J. Fernando Arévalo, María D. Pinazo-Durán and on behalf of the Valencia Study Group on Diabetic Retinopathy (VSDR) Report number 4
Antioxidants 2020, 9(11), 1101; https://doi.org/10.3390/antiox9111101 - 09 Nov 2020
Cited by 15 | Viewed by 2720
Abstract
Reactive oxygen species (ROS) overproduction and ROS-signaling pathways activation attack the eyes. We evaluated the oxidative stress (OS) and the effects of a daily, core nutritional supplement regimen containing antioxidants and omega 3 fatty acids (A/ω3) in type 2 diabetics (T2DM). A case-control [...] Read more.
Reactive oxygen species (ROS) overproduction and ROS-signaling pathways activation attack the eyes. We evaluated the oxidative stress (OS) and the effects of a daily, core nutritional supplement regimen containing antioxidants and omega 3 fatty acids (A/ω3) in type 2 diabetics (T2DM). A case-control study was carried out in 480 participants [287 T2DM patients with (+)/without (−) diabetic retinopathy (DR) and 193 healthy controls (CG)], randomly assigned to a daily pill of A/ω3. Periodic evaluation through 38 months allowed to outline patient characteristics, DR features, and classic/OS blood parameters. Statistics were performed by the SPSS 24.0 program. Diabetics displayed significantly higher circulating pro-oxidants (p = 0.001) and lower antioxidants (p = 0.0001) than the controls. Significantly higher plasma malondialdehyde/thiobarbituric acid reactive substances (MDA/TBARS; p = 0.006) and lower plasma total antioxidant capacity (TAC; p = 0.042) and vitamin C (0.020) was found in T2DM + DR versus T2DM-DR. The differential expression profile of solute carrier family 23 member 2 (SLC23A2) gene was seen in diabetics versus the CG (p = 0.001), and in T2DM + DR versus T2DM − DR (p < 0.05). The A/ω3 regime significantly reduced the pro-oxidants (p < 0.05) and augmented the antioxidants (p < 0.05). This follow-up study supports that a regular A/ω3 supplementation reduces the oxidative load and may serve as a dietary prophylaxis/adjunctive intervention for patients at risk of diabetic blindness. Full article
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13 pages, 3477 KiB  
Article
Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation
by Silvia Nistri, Claudia Fiorillo, Matteo Becatti and Daniele Bani
Antioxidants 2020, 9(9), 774; https://doi.org/10.3390/antiox9090774 - 21 Aug 2020
Cited by 13 | Viewed by 2383
Abstract
Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at [...] Read more.
Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low, nanomolar concentrations suggests that it specifically targets a common pathogenic mechanism of HR-induced damage, namely oxidative stress. In this study we offer experimental evidence that RLX (17 nmol L-1), added to the medium of HR-exposed H9c2 rat cardiac muscle cells, significantly reduces cell oxidative damage, mitochondrial dysfunction and apoptosis. These effects appear to rely on the up-regulation of the cellular availability of reduced glutathione (GSH), a ubiquitous endogenous antioxidant metabolite. Conversely, superoxide dismutase activity was not influenced by RLX, which, however, was not endowed with chemical antioxidant properties. Taken together, these findings verify the major pharmacological role of RLX in the protection against HR-induced oxidative stress, and shed first light on its mechanisms of action. Full article
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17 pages, 4479 KiB  
Article
Super-Resolution Microscopy Reveals an Altered Fibrin Network in Cirrhosis: The Key Role of Oxidative Stress in Fibrinogen Structural Modifications
by Matteo Becatti, Amanda Mannucci, Flavia Rita Argento, Stefano Gitto, Francesco Vizzutti, Fabio Marra, Niccolò Taddei, Claudia Fiorillo and Giacomo Laffi
Antioxidants 2020, 9(8), 737; https://doi.org/10.3390/antiox9080737 - 12 Aug 2020
Cited by 10 | Viewed by 2667
Abstract
Cirrhotic patients show a reduced synthesis of both pro- and anti-coagulant factors. Recent reports indicate that they are characterized by a higher risk of thrombotic rather than hemorrhagic complications, but the mechanisms conferring this risk are not fully elucidated. Oxidative-mediated fibrinogen modifications may [...] Read more.
Cirrhotic patients show a reduced synthesis of both pro- and anti-coagulant factors. Recent reports indicate that they are characterized by a higher risk of thrombotic rather than hemorrhagic complications, but the mechanisms conferring this risk are not fully elucidated. Oxidative-mediated fibrinogen modifications may explain, at least in part, a prothrombotic profile. The aim of the present pilot study was to investigate the alterations in fibrinogen structure and function in patients with cirrhosis of various severity and to correlate these findings with the mechanisms of thrombus formation. We assessed in plasma specific oxidative stress markers and measured oxidative modifications, functional and structural parameters in purified fibrinogen fractions obtained from cirrhotic patients and control subjects. We enrolled 15 cirrhotic patients (5 patients belonging to each of the three Child–Turcotte–Pugh classes) and 20 age- and sex-matched healthy controls. Plasma redox status, fibrinogen oxidative modifications, thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in cirrhotic patients and were associated to disease severity. Importantly, clot structure obtained by stimulated emission depletion (STED) super-resolution microscopy indicated modifications in fiber diameter and in clot porosity in cirrhotic patients. Fibrin fiber diameter significantly decreased in cirrhotic patients when compared to controls, and this difference became more marked with disease progression. In parallel, fibrin pore size progressively decreased along with disease severity. In cirrhotic patients, fibrinogen clot analysis and oxidative-dependent changes reveal novel structural and functional fibrinogen modifications which may favor thrombotic complications in cirrhosis. Full article
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12 pages, 634 KiB  
Article
Sex Difference Impacts on the Relationship between Paraoxonase-1 (PON1) and Type 2 Diabetes
by Valentina Rosta, Alessandro Trentini, Angelina Passaro, Giovanni Zuliani, Juana Maria Sanz, Cristina Bosi, Gloria Bonaccorsi, Tiziana Bellini and Carlo Cervellati
Antioxidants 2020, 9(8), 683; https://doi.org/10.3390/antiox9080683 - 29 Jul 2020
Cited by 8 | Viewed by 3184
Abstract
Type-2 diabetes (T2D) and its cardiovascular complications are related to sex. Increasing evidence suggests that paraoxonase 1 (PON1) activity, an antioxidant enzyme bound to high-density lipoproteins (HDL), is implicated in the onset and clinical progression of T2D. Since we previously showed that PON1 [...] Read more.
Type-2 diabetes (T2D) and its cardiovascular complications are related to sex. Increasing evidence suggests that paraoxonase 1 (PON1) activity, an antioxidant enzyme bound to high-density lipoproteins (HDL), is implicated in the onset and clinical progression of T2D. Since we previously showed that PON1 is a sexual dimorphic protein, we now investigated whether sex might impact the relationship between PON1 and this chronic disease. To address this aim, we assessed PON1 activity in the sera of 778 patients, including controls (women, n = 383; men, n = 198) and diabetics (women, n = 79; men = 118). PON1 activity decreased in both women and men with T2D compared with controls (p < 0.05 and p > 0.001, respectively), but the change was 50% larger in the female cohort. In line with this result, the enzyme activity was associated with serum glucose level only in women (r = −0.160, p = 0.002). Notably, only within this gender category, lower PON1 activity was independently associated with increased odds of being diabetic (odds ratio (95% Confidence interval: 2.162 (1.075–5.678)). In conclusion, our study suggests that PON1-deficiency in T2D is a gender-specific phenomenon, with women being more affected than men. This could contribute to the partial loss of female cardiovascular advantage associated with T2D. Full article
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Review

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21 pages, 1555 KiB  
Review
Cadmium-Induced Oxidative Stress: Focus on the Central Nervous System
by Jacopo J. V. Branca, Claudia Fiorillo, Donatello Carrino, Ferdinando Paternostro, Niccolò Taddei, Massimo Gulisano, Alessandra Pacini and Matteo Becatti
Antioxidants 2020, 9(6), 492; https://doi.org/10.3390/antiox9060492 - 05 Jun 2020
Cited by 131 | Viewed by 6113
Abstract
Cadmium (Cd), a category I human carcinogen, is a well-known widespread environmental pollutant. Chronic Cd exposure affects different organs and tissues, such as the central nervous system (CNS), and its deleterious effects can be linked to indirect reactive oxygen species (ROS) generation. Since [...] Read more.
Cadmium (Cd), a category I human carcinogen, is a well-known widespread environmental pollutant. Chronic Cd exposure affects different organs and tissues, such as the central nervous system (CNS), and its deleterious effects can be linked to indirect reactive oxygen species (ROS) generation. Since Cd is predominantly present in +2 oxidation state, it can interplay with a plethora of channels and transporters in the cell membrane surface in order to enter the cells. Mitochondrial dysfunction, ROS production, glutathione depletion and lipid peroxidation are reviewed in order to better characterize the Cd-elicited molecular pathways. Furthermore, Cd effects on different CNS cell types have been highlighted to better elucidate its role in neurodegenerative disorders. Indeed, Cd can increase blood–brain barrier (BBB) permeability and promotes Cd entry that, in turn, stimulates pericytes in maintaining the BBB open. Once inside the CNS, Cd acts on glial cells (astrocytes, microglia, oligodendrocytes) triggering a pro-inflammatory cascade that accounts for the Cd deleterious effects and neurons inducing the destruction of synaptic branches. Full article
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Other

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10 pages, 1763 KiB  
Brief Report
An Insight into Giant Cell Arteritis Pathogenesis: Evidence for Oxidative Stress and SIRT1 Downregulation
by Alessandro Ianni, Poonam Kumari, Shahriar Tarighi, Flavia Rita Argento, Eleonora Fini, Giacomo Emmi, Alessandra Bettiol, Thomas Braun, Domenico Prisco, Claudia Fiorillo and Matteo Becatti
Antioxidants 2021, 10(6), 885; https://doi.org/10.3390/antiox10060885 - 31 May 2021
Cited by 12 | Viewed by 2707
Abstract
Giant cell arteritis (GCA), medium and large vessel granulomatous vasculitis affecting the elderly, is characterized by a multitude of vascular complications, including venous thrombosis, myocardial infraction and stroke. The formation of granulomatous infiltrates and the enhanced accumulation of proinflammatory cytokines are typical features [...] Read more.
Giant cell arteritis (GCA), medium and large vessel granulomatous vasculitis affecting the elderly, is characterized by a multitude of vascular complications, including venous thrombosis, myocardial infraction and stroke. The formation of granulomatous infiltrates and the enhanced accumulation of proinflammatory cytokines are typical features of this condition. The GCA pathogenesis remains largely unknown, but recent studies have suggested the involvement of oxidative stress, mainly sustained by an enhanced reactive oxygen species (ROS) production by immature neutrophils. On this basis, in the present study, we intended to evaluate, in GCA patients, the presence of systemic oxidative stress and possible alterations in the expression level of nuclear sirtuins, enzymes involved in the inhibition of inflammation and oxidative stress. Thirty GCA patients were included in the study and compared to 30 healthy controls in terms of leukocyte ROS production, oxidative stress and SIRT1 expression. Our results clearly indicated a significant increase (p < 0.05) both in the ROS levels in the leukocyte fractions and plasma oxidative stress markers (lipid peroxidation and total antioxidant capacity) in the GCA patients compared to the healthy controls. In PBMCs from the GCA patients, a significant decrease in SIRT1 expression (p < 0.05) but not in SIRT6 and SIRT7 expression was found. Taken together, our preliminary findings indicate that, in GCA patients, plasma oxidative stress is paralleled by a reduced SIRT1 expression in PBMC. Further studies are needed to highlight if and how these alterations contribute to GCA pathogenesis. Full article
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