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Oxidative-Stress in Human Diseases—3rd Edition

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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 October 2024) | Viewed by 28056

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Dr. Soliman Khatib

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1. Department of Natural Products and Nutrition, MIGAL—Galilee Research Institute, Kiryat Shmona 11016, Israel 2. Faculty of Sciences, Tel Hai Academic College, Qiryat Shemona 12208, Israel
Interests: natural compounds; analytical chemistry; metabolomics; oxidative stress; atherosclerosis
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Dear Colleagues,

Oxidative stress (OS) is essential in the pathogenesis of human chronic diseases such as cardiovascular and kidney diseases, diabetes, neurodegenerative disorders, cancer, inflammation-related diseases, and aging. OS is a condition characterized by an imbalance between the production and accumulation of oxygen and nitrogen reactive species (ROS/RNS) in cells and tissues, and it occurs when the generation of these compounds exceeds the ability of the biological system to neutralize them.

ROS/RNS, such as superoxide (O₂^•−), hydrogen peroxide (H₂O₂), hydroxyl radical (HO^•), nitrogen oxide (NO^•), peroxynitrite (ONOO⁻), and hypochlorous acid (HOCl), are all products of normal metabolic pathways in humans; their production may increase as a result of influential external factors, such as pollution, cigarette smoke, or internally, as a result of impaired intracellular metabolism. Long-term exposure to increased levels of ROS/RNS can cause structural defects of lipids, proteins, DNA, and RNA, as well as the functional alteration of several enzymes and cellular structures, leading to an increase in OS and pathogenesis.

We invite you to share your latest original and innovative research findings or review articles in this upcoming Special Issue, “Oxidative-Stress in Human Diseases—3rd Edition”. We welcome clinical and pre-clinical studies on the relationship between OS and human diseases, novel diagnosis methods and mechanisms, as well as approaches for preventing and treating diseases related to OS.

Dr. Soliman Khatib
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

oxidative stress
ROS/RNS
human diseases
antioxidants
OS biomarkers

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Published Papers (11 papers)

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Research

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12 pages, 1702 KiB

Open AccessArticle

How Antiretroviral Drug Concentrations Could Be Affected by Oxidative Stress, Physical Capacities and Genetics: A Focus on Dolutegravir Treated Male PLWH

by Jessica Cusato, Anna Mulasso, Micol Ferrara, Alessandra Manca, Guido Accardo, Alice Palermiti, Miriam Antonucci, Gianluca Bianco, Francesco Chiara, Jacopo Mula, Maria Cristina Tettoni, Simone Cuomo, Giulia Trevisan, Stefano Bonora, Giovanni Di Perri, Corrado Lupo, Alberto Rainoldi and Antonio D’Avolio

Antioxidants 2025, 14(1), 82; https://doi.org/10.3390/antiox14010082 - 13 Jan 2025

Viewed by 959

Abstract

High levels of reactive oxygen species (ROS) are present in people living with HIV (PLWH), produced by intense physical activity; in response, our body produces antioxidant molecules. ROS influence the expression of gene-encoding enzymes and transporters involved in drug biotransformation. In addition, pharmacogenetics can influence transporter activity, and thus drug exposure. Currently, no studies concerning this topic are present in the literature. The aim of this study was to investigate whether some antioxidant molecules, physical exercise, and genetic variants could affect dolutegravir (DTG) concentrations in PLWH, switching from triple to dual therapy. Thirty PLWH were recruited and analyzed at baseline (triple therapy), and 6 months after (dual therapy). Physical capacities were investigated using validated tools. Drug concentrations and oxidative stress biomarkers levels were evaluated through liquid chromatography coupled with tandem mass spectrometry, while genetic variants through real-time PCR. No statistical differences were suggested for drug concentrations, with the exception of intracellular DTG (p = 0.047). Statistically significant correlations between DTG plasma concentrations and white blood cells (p = 0.011; S = 0.480) and cytoplasmic N-acetyl-cysteine (p = 0.033; S = −0.419) were observed. Finally, white blood cells and BMI remained in the final multivariate regression model as predictors of DTG concentrations. This is the first study showing possible factors related to oxidative stress impacting DTG exposure. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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19 pages, 3777 KiB

Open AccessArticle

Interventions by Cardiovascular Drugs Against Aircraft Noise-Induced Cardiovascular Oxidative Stress and Damage

by Marin Kuntić, Ivana Kuntić, Jiayin Zheng, Leonardo Nardi, Matthias Oelze, Arijan Valar, Dominika Mihaliková, Lea Strohm, Henning Ubbens, Qi Tang, Liyu Zhang, Guilherme Horta, Paul Stamm, Omar Hahad, Dilja Krueger-Burg, Huige Li, Sebastian Steven, Adrian Gericke, Michael J. Schmeisser, Thomas Münzel and Andreas Daiber Show full author list Hide full author list

Antioxidants 2025, 14(1), 59; https://doi.org/10.3390/antiox14010059 - 7 Jan 2025

Viewed by 1328

Abstract

Noise pollution is a known health risk factor and evidence for cardiovascular diseases associated with traffic noise is growing. At least 20% of the European Union’s population lives in noise-polluted areas with exposure levels exceeding the recommended limits of the World Health Organization, which is considered unhealthy by the European Environment Agency. This results in the annual loss of 1.6 million healthy life years. Here, we investigated the protective effects of cardiovascular drug interventions against aircraft noise-mediated cardiovascular complications such as elevated oxidative stress or endothelial dysfunction. Using our established mouse exposure model, we applied mean sound pressure levels of 72 dB(A) for 4 d. C57BL/6 mice were treated with the beta-blocker propranolol (15 mg/kg/d s.c. for 5 d) or the alpha-blocker phenoxybenzamine (1.5 mg/kg/d s.c. for 5 d) and noise-exposed for the last 4 d of the drug administration. Short-term noise exposure caused hypertension (measured by tail-cuff blood pressure monitoring) and impaired endothelial function (measured by isometric tension recording in the aorta and video microscopy in cerebral arterioles in response to acetylcholine). Noise also increased markers of oxidative stress and inflammation. Treatment of mice with propranolol and phenoxybenzamine prevented endothelial and microvascular dysfunction, which was supported by a decrease in markers of inflammation and oxidative stress in heart tissue and the brain. Amelioration of noise-induced hypertension (systolic blood pressure) was not observed, whereas pulse pressure was lowered by trend. This study provides a novel perspective mitigating the adverse effects of noise pollution, especially in vulnerable groups with medication, a rationale for further pharmacological human studies. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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15 pages, 3956 KiB

Open AccessArticle

Withania somnifera (Ashwagandha) Improves Spatial Memory, Anxiety and Depressive-like Behavior in the 5xFAD Mouse Model of Alzheimer’s Disease

by Noah Gladen-Kolarsky, Olivia Monestime, Melissa Bollen, Jaewoo Choi, Liping Yang, Armando Alcazar Magaña, Claudia S. Maier, Amala Soumyanath and Nora E. Gray

Antioxidants 2024, 13(10), 1164; https://doi.org/10.3390/antiox13101164 - 25 Sep 2024

Cited by 2 | Viewed by 3830

Abstract

Withania somnifera (WS), also known as ashwagandha, is a popular botanical supplement used to treat various conditions including memory loss, anxiety and depression. Previous studies from our group showed an aqueous extract of WS root (WSAq) enhances cognition and alleviates markers for depression in Drosophila. Here, we sought to confirm these effects in the 5xFAD mouse model of β-amyloid (Aβ) accumulation. Six- to seven-month-old male and female 5xFAD mice were treated with WSAq in their drinking water at 0 mg/mL, 0.5 mg/mL or 2.5 mg/mL for four weeks. In the fourth week of treatment, spatial memory, anxiety and depressive-like symptoms were evaluated. At the conclusion of behavioral testing, brain tissue was harvested, immunohistochemistry was performed, and the cortical expression of antioxidant response genes was evaluated. Both concentrations of WSAq improved spatial memory and reduced depressive and anxiety-related behavior. These improvements were accompanied by a reduction in Aβ plaque burden in the hippocampus and cortex and an attenuation of activation of microglia and astrocytes. Antioxidant response genes were upregulated in the cortex of WSAq-treated mice. Oral WSAq treatment could be beneficial as a therapeutic option in AD for improving disease pathology and behavioral symptoms. Future studies focused on dose optimization of WSAq administration and further assessment of the mechanisms by which WSAq elicits its beneficial effects will help inform the clinical potential of this promising botanical therapy. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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13 pages, 1681 KiB

Open AccessArticle

Trehalose Protects against Superoxide Dismutase 1 Proteinopathy in an Amyotrophic Lateral Sclerosis Model

by Rayne S. S. Magalhães, José R. Monteiro Neto, Gabriela D. Ribeiro, Luan H. Paranhos and Elis C. A. Eleutherio

Antioxidants 2024, 13(7), 807; https://doi.org/10.3390/antiox13070807 - 3 Jul 2024

Cited by 1 | Viewed by 1440

Abstract

This work aimed to study the effect of trehalose in protecting cells against Sod1 proteinopathy associated with amyotrophic lateral sclerosis (ALS). Humanized yeast cells in which native Sod1 was replaced by wild-type human Sod1 or an ALS mutant (WT-A4V Sod1 heterodimer) were used as the experimental model. Cells were treated with 10% trehalose (p/v) before or after the appearance of hSod1 proteinopathy induced by oxidative stress. In both conditions, trehalose reduced the number of cells with Sod1 inclusions, increased Sod1 activity, and decreased the levels of intracellular oxidation, demonstrating that trehalose avoids Sod1 misfolding and loss of function in response to oxidative stress. The survival rates of ALS Sod1 cells stressed in the presence of trehalose were 60% higher than in their absence. Treatment with trehalose after the appearance of Sod1 inclusions in cells expressing WT Sod1 doubled longevity; after 5 days, non-treated cells did not survive, but 15% of cells treated with sugar were still alive. Altogether, our results emphasize the potential of trehalose as a novel therapy, which might be applied preventively in ALS patients with a family history of the disease or after diagnosis in ALS patients who discover the disease following the first symptoms. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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19 pages, 1487 KiB

Open AccessArticle

Catalase, Glutathione Peroxidase, and Peroxiredoxin 2 in Erythrocyte Cytosol and Membrane in Hereditary Spherocytosis, Sickle Cell Disease, and β-Thalassemia

by Daniela Melo, Fátima Ferreira, Maria José Teles, Graça Porto, Susana Coimbra, Susana Rocha and Alice Santos-Silva

Antioxidants 2024, 13(6), 629; https://doi.org/10.3390/antiox13060629 - 22 May 2024

Cited by 2 | Viewed by 2187

Abstract

Catalase (CAT), glutathione peroxidase (GPx), and peroxiredoxin 2 (Prx2) can counteract the deleterious effects of oxidative stress (OS). Their binding to the red blood cell (RBC) membrane has been reported in non-immune hemolytic anemias (NIHAs). Our aim was to evaluate the relationships between CAT, GPx, and Prx2, focusing on their role at the RBC membrane, in hereditary spherocytosis (HS), sickle cell disease (SCD), β-thalassemia (β-thal), and healthy individuals. The studies were performed in plasma and in the RBC cytosol and membrane, evaluating OS biomarkers and the enzymatic activities and/or the amounts of CAT, GPx, and Prx2. The binding of the enzymes to the membrane appears to be the primary protective mechanism against oxidative membrane injuries in healthy RBCs. In HS (unsplenectomized) and β-thal, translocation from the cytosol to the membrane of CAT and Prx2, respectively, was observed, probably to counteract lipid peroxidation. RBCs from splenectomized HS patients showed the highest membrane-bound hemoglobin, CAT, and GPx amounts in the membrane. SCD patients presented the lowest amount of enzyme linkage, possibly due to structural changes induced by sickle hemoglobin. The OS-induced changes and antioxidant response were different between the studied NIHAs and may contribute to the different clinical patterns in these patients. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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Review

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19 pages, 1231 KiB

Open AccessReview

Antioxidant Properties of Albumin and Diseases Related to Obstetrics and Gynecology

by Kazushi Watanabe, Hiroyuki Kinoshita, Tomohito Okamoto, Kazumasa Sugiura, Shingo Kawashima and Tetsuro Kimura

Antioxidants 2025, 14(1), 55; https://doi.org/10.3390/antiox14010055 - 6 Jan 2025

Viewed by 1273

Abstract

Albumin, the most abundant protein, contributes significantly to various physiological processes, indicating its multifunctional properties. It has drawn the attention of scientists and physicians because of its primary role in maintaining osmotic pressure and involvement in transporting numerous small molecules, including hormones, fatty acids, and drugs. A growing body of evidence has recently illustrated an additional aspect of albumin’s antioxidant properties. Therefore, based on recent research findings, this review article delves into the molecular and biochemical aspects of albumin’s antioxidative capabilities. We highlight the multifaceted significance of proteins in oxidative stress and their relation to pathologies in obstetrics and gynecology. In particular, we focused on preeclampsia, in which oxidative stress is closely involved in the pathogenesis, and renal dysfunction leads to increased albumin excretion into the urine, resulting in hypoalbuminemia. In addition, we discussed the role of albumin in preeclampsia pathogenesis, diagnosis, and patient prognosis. Understanding the antioxidant properties of albumin opens new avenues for therapeutic intervention and sheds light on novel strategies for combating preeclampsia associated with oxidative damage. In this study, we employed the PubMed database to search for articles that assessed the antioxidant properties of albumin, with a specific focus on obstetric diseases, particularly preeclampsia. The last update of the search was conducted in November 2024. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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23 pages, 975 KiB

Open AccessReview

MnSOD Mimetics in Therapy: Exploring Their Role in Combating Oxidative Stress-Related Diseases

by Jovan Grujicic and Antiño R. Allen

Antioxidants 2024, 13(12), 1444; https://doi.org/10.3390/antiox13121444 - 23 Nov 2024

Cited by 1 | Viewed by 1500

Abstract

Reactive oxygen species (ROS) are double-edged swords in biological systems—they are essential for normal cellular functions but can cause damage when accumulated due to oxidative stress. Manganese superoxide dismutase (MnSOD), located in the mitochondrial matrix, is a key enzyme that neutralizes superoxide radicals (O₂^•−), maintaining cellular redox balance and integrity. This review examines the development and therapeutic potential of MnSOD mimetics—synthetic compounds designed to replicate MnSOD’s antioxidant activity. We focus on five main types: Mn porphyrins, Mn salens, MitoQ10, nitroxides, and mangafodipir. These mimetics have shown promise in treating a range of oxidative stress-related conditions, including cardiovascular diseases, neurodegenerative disorders, cancer, and metabolic syndromes. By emulating natural antioxidant defenses, MnSOD mimetics offer innovative strategies to combat diseases linked to mitochondrial dysfunction and ROS accumulation. Future research should aim to optimize these compounds for better stability, bioavailability, and safety, paving the way for their translation into effective clinical therapies. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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20 pages, 1017 KiB

Open AccessReview

Oxidative Stress and Antioxidants in Pediatric Asthma’s Evolution and Management

by Ileana Katerina Ioniuc, Ancuta Lupu, Felicia Dragan, Irina Tarnita, Monica Mihaela Alexoae, Violeta Streanga, Costica Mitrofan, Aye Aung Thet, Alin Horatiu Nedelcu, Delia Lidia Salaru, Stefan Lucian Burlea, Elena Cristina Mitrofan, Vasile Valeriu Lupu and Alice Nicoleta Azoicai

Antioxidants 2024, 13(11), 1331; https://doi.org/10.3390/antiox13111331 - 31 Oct 2024

Cited by 9 | Viewed by 1878

Abstract

Within the pediatric population, bronchial asthma is one of the most prevalent chronic respiratory system diseases. The number of exacerbations, severity, and duration of symptoms all have a significant impact on children’s life quality. In the last decades, the prevention and management strategies of this pathology have focused on maintaining or even increasing the pulmonary function to maximum levels in early childhood, as it has been demonstrated that functional deficits at this level occurring before school age cause pathological manifestations later, in adulthood. The epithelium of the airways and implicitly that of the lung is the first barrier against the lesions caused by pro-oxidative factors. Both oxidative and antioxidative factors can be of endogenous origin (produced by the body) or exogenous (from the environment or diet). Good functioning of antioxidant defense mechanisms from the molecular level to the tissue level, and a balance between pro-oxidative factors and anti- oxidative factors, influence the occurrence of compensatory mechanisms at the level of the respiratory epithelium, causing the delay of local responses to the stress induced by chronic inflammation (bronchial remodeling, thickening of airway smooth muscles, bronchoconstriction, bronchial hyper-reactivity). These mechanisms underlie the pathophysiological changes in asthma. Numerous studies carried out among the pediatric population inclusively have demonstrated the effectiveness of antioxidants in the prophylaxis, slowing down and preventing the progression of this pathology. This review complements the scientific articles, aiming at emphasizing the complexity of oxidative physio-pathological pathways and their importance in the occurrence, development, and therapeutic response in asthma, providing a good understanding of the relationship between oxidative and antioxidative factors, and being a source of future therapeutic strategies. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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19 pages, 959 KiB

Open AccessReview

The Double-Edged Sword of Total Antioxidant Capacity: Clinical Significance and Personal Experience

by Andrea Silvestrini and Antonio Mancini

Antioxidants 2024, 13(8), 933; https://doi.org/10.3390/antiox13080933 - 1 Aug 2024

Viewed by 1884

Abstract

Oxidative stress (OS) could be a condition underlying several human diseases, despite the physiological role of reactive oxygen species (oxidative eustress). Therefore, antioxidant compounds could represent a modulatory mechanism for maintaining a proper redox balance and redox signaling. When antioxidants are insufficient or overwhelmed, OS ensues, causing multiple damages at molecular, tissue, and cellular levels. This study focuses on the role of total antioxidant capacity (TAC) as a biomarker to be interpreted according to several clinical scenarios. After a brief description of various assay methods to elucidate terminology and physiopathological roles, we focus on the hormonal influence on TAC in blood plasma and other biological fluids, as different endocrine systems can modulate the antioxidant response. Furthermore, OS characterizes several endocrinopathies through different mechanisms: an inadequate antioxidant response to an increase in reducing equivalents (reductive distress) or a marked consumption of antioxidants (oxidative distress), which leads to low TAC values. An increased TAC could instead represent an adaptive mechanism, suggesting a situation of OS. Hence, the clinical context is fundamental for a correct interpretation of TAC. This review aims to provide the reader with a general overview of oxidative stress in several clinical examples of endocrine relevance, such as metabolic syndrome, non-thyroid illness syndrome, hypopituitarism, and infertility. Finally, the impact of dietary and surgical interventions on TAC in the model of metabolic syndrome is highlighted, along with personal experience. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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22 pages, 971 KiB

Open AccessReview

Traditional Chinese Medicine for Hashimoto’s Thyroiditis: Focus on Selenium and Antioxidant Phytochemicals

by Sheng Huang, Panos G. Ziros, Dionysios V. Chartoumpekis, Georgios Psarias, Leonidas Duntas, Xinhe Zuo, Xinyi Li, Zhiguo Ding and Gerasimos P. Sykiotis

Antioxidants 2024, 13(7), 868; https://doi.org/10.3390/antiox13070868 - 19 Jul 2024

Cited by 2 | Viewed by 6888

Abstract

Hashimoto’s thyroiditis (HT) is not only the most frequent autoimmune thyroid disease (AITD), but it also has a significant impact on patients’ health-related quality of life (HRQoL), and it has been variably associated with differentiated thyroid carcinoma. Even though its pathogenesis is still incompletely understood, oxidative stress is believed to play an important role. Hypothyroidism related to later stages of HT can be treated with levothyroxine substitution therapy; various approaches such as selenium supplementation and iodine-restricted diets have been proposed as disease-modifying treatments for earlier stages, and even thyroidectomy has been suggested for refractory cases of painful HT. Nevertheless, many patients still report suboptimal HRQoL, highlighting an unmet medical need in this area. The concepts and approaches of traditional Chinese medicine (TCM) in treating HT are not broadly known in the West. Here, we provide an overview of TCM for HT, including combinations of TCM with selenium. We encompass evidence from clinical trials and other studies related to complex TCM prescriptions, single herbs used in TCM, and phytochemicals; wherever possible, we delineate the probable underlying molecular mechanisms. The findings show that the main active components of TCM for HT have commonly known or presumed antioxidant and anti-inflammatory activities, which may account for their potential utility in HT. Further exploring the practices of TCM for HT and combining them with evidence- and mechanism-based approaches according to Western standards may help to identify new strategies to alter the clinical course of the disease and/or to treat patients’ symptoms better and improve their HRQoL. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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34 pages, 3523 KiB

Open AccessSystematic Review

Oxidative Stress and Mitochondria Are Involved in Anaphylaxis and Mast Cell Degranulation: A Systematic Review

by Anays Piotin, Walid Oulehri, Anne-Laure Charles, Charles Tacquard, Olivier Collange, Paul-Michel Mertes and Bernard Geny

Antioxidants 2024, 13(8), 920; https://doi.org/10.3390/antiox13080920 - 29 Jul 2024

Cited by 2 | Viewed by 3692

Abstract

Anaphylaxis, an allergic reaction caused by the massive release of active mediators, can lead to anaphylactic shock (AS), the most severe and potentially life-threatening form of anaphylactic reaction. Nevertheless, understanding of its pathophysiology to support new therapies still needs to be improved. We performed a systematic review, assessing the role and the complex cellular interplay of mitochondria and oxidative stress during anaphylaxis, mast cell metabolism and degranulation. After presenting the main characteristics of anaphylaxis, the oxidant/antioxidant balance and mitochondrial functions, we focused this review on the involvement of mitochondria and oxidative stress in anaphylaxis. Then, we discussed the role of oxidative stress and mitochondria following mast cell stimulation by allergens, leading to degranulation, in order to further elucidate mechanistic pathways. Finally, we considered potential therapeutic interventions implementing these findings for the treatment of anaphylaxis. Experimental studies evaluated mainly cardiomyocyte metabolism during AS. Cardiac dysfunction was associated with left ventricle mitochondrial impairment and lipid peroxidation. Studies evaluating in vitro mast cell degranulation, following Immunoglobulin E (IgE) or non-IgE stimulation, revealed that mitochondrial respiratory complex integrity and membrane potential are crucial for mast cell degranulation. Antigen stimulation raises reactive oxygen species (ROS) production from nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and mitochondria, leading to mast cell degranulation. Moreover, mast cell activation involved mitochondrial morphological changes and mitochondrial translocation to the cell surface near exocytosis sites. Interestingly, antioxidant administration reduced degranulation by lowering ROS levels. Altogether, these results highlight the crucial role of oxidative stress and mitochondria during anaphylaxis and mast cell degranulation. New therapeutics against anaphylaxis should probably target oxidative stress and mitochondria, in order to decrease anaphylaxis-induced systemic and major organ deleterious effects. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—3rd Edition)

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