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The Role of Oxidative Stress and Antioxidants in Human Disease

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 May 2026 | Viewed by 17565

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Dr. Federica Mannino

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Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy
Interests: pharmacology; natural products; oxidative stress; inflammatory disease; atherosclerosis; metabolic disease; neurodegenerative diseases; autophagy; proliferation and differentiation process
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Dear Colleagues,

Oxidative stress is a condition where there is an imbalance between free radicals (reactive oxygen species) and antioxidants in the body. Free radicals are highly reactive molecules that can damage cells, proteins, and DNA, contributing to aging and various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. Antioxidants are molecules that neutralize free radicals, preventing or reducing damage. Natural antioxidants, such as vitamins C and E, polyphenols, and flavonoids, are found in fruits, vegetables, nuts, and whole grains. They play a crucial role in maintaining health by protecting cells from oxidative damage. The body also produces endogenous antioxidants, like glutathione, which further defend against oxidative stress. Balancing oxidative stress with sufficient antioxidants is essential for preventing chronic diseases and promoting overall well-being. Consuming a diet rich in natural antioxidants is a key strategy for managing oxidative stress.

This Special Issue will focus on new insights into the role of oxidative stress and antioxidants in human diseases.

Dr. Federica Mannino
Guest Editor

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Keywords

oxidative stress
free radicals
antioxidants
reactive oxygen species (ROS)
polyphenols

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Published Papers (7 papers)

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Research

Jump to: Review

14 pages, 606 KB

Open AccessArticle

A Pilot Study on the Potential Pathological Link Between Oxidative Stress Markers and Renal Function in People Living with HIV

by Joel Choshi, Haskly Mokoena, Helen C. Steel, Brian T. Flepisi, Kabelo Mokgalaboni, Wendy N. Phoswa, Gerald Maarman, Sihle E. Mabhida, Bongani B. Nkambule, Phiwayinkosi V. Dludla and Sidney Hanser

Int. J. Mol. Sci. 2025, 26(23), 11429; https://doi.org/10.3390/ijms262311429 - 26 Nov 2025

Viewed by 750

Abstract

Human immunodeficiency virus (HIV) infection remains a major health burden in Sub-Saharan Africa, despite the widespread use of antiretroviral therapy (ART). Oxidative stress contributes to HIV-related comorbidities, including renal dysfunction. However, the role of oxidative stress in kidney impairment among people living with HIV (PLWH) is not fully understood. This cross-sectional study included PLWH on ART (n = 80), PLWH without ART (n = 27), and people not living with HIV (PNLWH) (n = 44). Oxidative stress was measured by serum malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (TAC), while renal function was assessed using cystatin C-based estimated glomerular filtration rate (eGFR_cystC). Participants on ART were older (median 43 years) and had higher CD4+ T-cell counts compared to those not on ART. PLWH on ART showed significantly elevated MDA levels compared to PLWH without ART (p < 0.001) and PNLWH (p = 0.001). There was no difference in superoxide dismutase (SOD) and TAC levels among the groups (p = 0.177 and 0.888, respectively). Among PLWH, MDA was higher in those with reduced renal function (eGFR_cystC < 90) versus normal function (p < 0.05). In PLWH on ART, SOD activity was significantly lower in mild renal impairment (eGFR_cystC 60–89) compared to normal function (p = 0.017), but no difference was observed in the TAC levels (p = 0.883). In PLWH on ART, regression analyses indicated no independent association between MDA and renal function decline, while higher SOD activity independently predicted better renal function (adjusted β = 2.26, p = 0.042). Oxidative damage accompanied by the inability of the body’s primary antioxidant defenses may be present at the early onset of renal function decline in PLWH. Superoxide dismutase, as an antioxidant defence enzyme, may be a key contributor to renal health in PLWH on ART. Future studies with larger cohorts and longitudinal designs are needed to clarify these relationships emanating from this pilot study. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress and Antioxidants in Human Disease)

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22 pages, 4978 KB

Open AccessArticle

Endotoxin Pretreatment Mitigates Myocardial Ischemia-Reperfusion Injury Through Preservation of Mitochondrial Respiration: A Combined Assessment of In Vivo, Ex Vivo, and In Vitro Data

by Reverien Habimana, Jiae Seong, YeongEun Jo, Ryul-Hee Kim, Hyo-Jung Kim, Kyung Soon Choi, Mukhammad Kayumov, Francis O. Obiweluozor, Wang-In Kim, Hwa Jin Cho, Dowan Kim, Kook Joo Na and Inseok Jeong

Int. J. Mol. Sci. 2025, 26(22), 11162; https://doi.org/10.3390/ijms262211162 - 19 Nov 2025

Viewed by 947

Abstract

Acute myocardial infarction is the most common form of coronary artery disease, and myocardial ischemia–reperfusion injury remains a major challenge despite advances in reperfusion therapy. Endotoxin preconditioning has been linked to reduced ischemia–reperfusion injury, but mechanisms remain unclear, and prior studies have used varied assessment methods with inconsistent results. In this study, we confirmed the protective effect of endotoxin preconditioning and assessed its role in preserving mitochondrial respiration using a multi-model approach of in vivo ischemia–reperfusion rat model, ex vivo normothermic rat heart perfusion, and in vitro hypoxia–reoxygenation in neonatal rat cardiomyocytes. Hemodynamic and cell-based analyses were performed in control (n = 5), ischemia–reperfusion/hypoxia–reoxygenation (n = 4/3), and endotoxin-pretreated (n = 5/3) groups. Low-dose endotoxin pretreatment significantly preserved left ventricular function, myocardial oxygen consumption, and mitochondrial respiration (p < 0.001). Preservation of function was associated with reduced hypoxia-inducible factor 1-alpha (HIF-1α) expression and decreased mitochondrial superoxide production, indicating reduced oxidative stress. Nonlethal endotoxin pretreatment protects the myocardium from ischemia–reperfusion injury by sustaining mitochondrial respiration and limiting oxidative damage. These findings support further investigation in large animal models to better replicate human myocardial infarction and evaluate translational potential. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress and Antioxidants in Human Disease)

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12 pages, 1268 KB

Open AccessArticle

The Effects of Lutein-Containing Supplement Intake on Glycation Inhibition Among Diabetic Patients with Cataracts

by Rijo Hayashi, Shimmin Hayashi and Shigeki Machida

Int. J. Mol. Sci. 2025, 26(12), 5706; https://doi.org/10.3390/ijms26125706 - 13 Jun 2025

Viewed by 2535

Abstract

Glycation is known as an important factor inducing human diseases, including diabetic complications. As oxidative stress contributes to procedures of glycation, antioxidants may inhibit glycation and delay the progression of diabetic complications. Our previous investigation of human aqueous humor after the intake of a lutein-containing supplement demonstrated increases in antioxidative activities and decreases in peroxidative products. This study enrolled 25 patients with diabetes (DM group) and 100 age-matched controls. Aqueous humor samples were collected during cataract surgery before and after 6 weeks of oral intake of the lutein-containing antioxidant supplement, Ocuvite + Lutein^®. The carboxymethyl-lysine level (CML) was measured as an indicator of glycation. Levels of superoxide dismutase activities (SOD) and total hydroperoxide (TH) were measured as indicators of oxidation. Changes after intake and the differences between age-matched controls and the DM group were evaluated. CML decreased after intake among the DM group, while there were no changes among the age-matched controls. SOD was significantly lower and TH was significantly higher in the DM group as compared to the age-matched controls, both before and after intake. In line with the decreases in glycation, the intake of lutein-containing antioxidant supplements may inhibit diabetic complications in diabetic patients. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress and Antioxidants in Human Disease)

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16 pages, 1573 KB

Open AccessArticle

Peumus boldus Extract Inhibits Lipid Accumulation in 3T3-L1 Adipocytes

by Laura Montaldo, Llerson Bendezu Meza, Mauricio De Marzi and Liliana Noemi Guerra

Int. J. Mol. Sci. 2025, 26(9), 4326; https://doi.org/10.3390/ijms26094326 - 2 May 2025

Cited by 1 | Viewed by 1714

Abstract

Obesity is a metabolic condition of epidemic scale. Previously, we showed that antioxidant extracts from Ribes nigrum had antioxidant and anti-adipogenic effects in mature adipocytes (AD). Here, we evaluated an aqueous extract from Peumus boldus (Boldo) in AD and studied its effect on reactive oxygen species (ROS) and lipid production. We analyzed the antioxidant activity (AA) of the Boldo extract using the DPPH technique and polyphenol (Pph) content via Folin’s reagent. In AD, we evaluated ROS production, catalase (CAT) activity, intracellular triglyceride (Tg) and cholesterol (Chol) contents, nitric oxide (NO) production via Griess reagent, and the levels of glycerol (Gly) and TNF-α released in the culture medium. We showed that the Boldo extract has high AA. In vitro, Boldo treatment decreased ROS intracellular production and CAT activity. In addition, the Boldo extract was effective in reducing Tg and Chol levels and NO production. We did not identify significant differences in Gly released or TNF-α secreted. We suggest that the Boldo extract has antioxidant and anti-adipogenic effects, but we did not observe lipolytic effects. Boldo did not modify inflammatory markers. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress and Antioxidants in Human Disease)

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23 pages, 6999 KB

Open AccessArticle

Beneficial Antioxidant Effects of Coenzyme Q10 in In Vitro and In Vivo Models of CDKL5 Deficiency Disorder

by Manuela Loi, Francesca Valenti, Giorgio Medici, Nicola Mottolese, Giulia Candini, Angelica Marina Bove, Federica Trebbi, Luca Pincigher, Romana Fato, Christian Bergamini, Stefania Trazzi and Elisabetta Ciani

Int. J. Mol. Sci. 2025, 26(5), 2204; https://doi.org/10.3390/ijms26052204 - 28 Feb 2025

Cited by 4 | Viewed by 4150

Abstract

CDKL5 deficiency disorder (CDD), a developmental encephalopathy caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene, is characterized by a complex and severe clinical picture, including early-onset epilepsy and cognitive, motor, visual, and gastrointestinal disturbances. This disease still lacks a medical treatment to mitigate, or reverse, its course and improve the patient’s quality of life. Although CDD is primarily a genetic brain disorder, some evidence indicates systemic abnormalities, such as the presence of a redox imbalance in the plasma and skin fibroblasts from CDD patients and in the cardiac myocytes of a mouse model of CDD. In order to shed light on the role of oxidative stress in the CDD pathophysiology, in this study, we aimed to investigate the therapeutic potential of Coenzyme Q10 (CoQ10), which is known to be a powerful antioxidant, using in vitro and in vivo models of CDD. We found that CoQ10 supplementation not only reduces levels of reactive oxygen species (ROS) and normalizes glutathione balance but also restores the levels of markers of DNA damage (γ-H2AX) and senescence (lamin B1), restoring cellular proliferation and improving cellular survival in a human neuronal model of CDD. Importantly, oral supplementation with CoQ10 exerts a protective role toward lipid peroxidation and DNA damage in the heart of a murine model of CDD, the Cdkl5 (+/−) female mouse. Our results highlight the therapeutic potential of the antioxidant supplement CoQ10 in counteracting the detrimental oxidative stress induced by CDKL5 deficiency. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress and Antioxidants in Human Disease)

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Review

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15 pages, 650 KB

Open AccessReview

Sustained Activation of Myeloperoxidase Is Associated with Oxidative Stress and Inflammation in People Living with the Human Immunodeficiency Virus at Risk of Cardiovascular Disease

by Haskly Mokoena, Joel Choshi, Sidney Hanser, Sihle E. Mabhida, Helen C. Steel, Kabelo Mokgalaboni, Wendy N. Phoswa, Gerald Maarman, Bongani B. Nkambule and Phiwayinkosi V. Dludla

Int. J. Mol. Sci. 2025, 26(21), 10285; https://doi.org/10.3390/ijms262110285 - 22 Oct 2025

Cited by 1 | Viewed by 1604

Abstract

People living with the human immunodeficiency virus (PLWH) are continually subjected to challenges involving the development of non-acquired immunodeficiency syndrome (AIDS)-related comorbidities despite the effectiveness of highly active antiretroviral therapy (HAART). Exacerbated oxidative stress, which is intrinsically linked to chronic inflammation, is implicated in non-AIDS comorbidities, including the increased risk of cardiovascular disease (CVD) observed in PLWH. Here, we review evidence on the potential pathological implications of myeloperoxidase (MPO), a leukocyte-derived enzyme and a key mediator of oxidative stress and inflammation, in driving CVD-related complications in PLWH. A systematic review approach was taken to identify relevant clinical studies through searches of Cochrane Libraries, PubMed, Web of Science, ScienceDirect, and Google Scholar, up to the 30 June 2025. The summarized data appraised clinical studies (n = 14) on adults (n = 1445) with a mean age of 45 years reporting on the association between MPO and enhanced lipid peroxidation marked by elevated concentrations of oxidized low-density lipoprotein cholesterol (oxLDL-C) in PLWH. Such results were consistent with elevated inflammatory markers, including high sensitivity C-reactive protein (hsCRP), which was also linked with endothelial dysfunction. There is a lack of evidence linking the duration of HAART to MPO levels or an increased risk of CVD. However, there is room to explore whether enhanced levels of oxLDL-C, in association with sustained MPO activation, could drive CVD risk in PLWH. The present review provides essential information on the pathological relevance of MPO in endothelial dysfunction and CVD risk in PLWH. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress and Antioxidants in Human Disease)

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15 pages, 792 KB

Open AccessReview

Impact of Reductive Stress on Human Infertility: Underlying Mechanisms and Perspectives

by Efthalia Moustakli, Athanasios Zikopoulos, Charikleia Skentou, Periklis Katopodis, Ekaterini Domali, Anastasios Potiris, Sofoklis Stavros and Athanasios Zachariou

Int. J. Mol. Sci. 2024, 25(21), 11802; https://doi.org/10.3390/ijms252111802 - 2 Nov 2024

Cited by 21 | Viewed by 4408

Abstract

Antioxidants have a well-established effect on general health and are essential in preventing oxidative damage to cells by scavenging free radicals. Free radicals are thought to be neutralized by these substances, which include polyphenols, β-carotene, and vitamins C and E, reducing cellular damage. On the other hand, recent data indicates that consuming excessive amounts of antioxidants may have side effects. Apoptosis and cell signaling are two beneficial physiological processes that are affected by excessive supplementation. Other negative effects include paradoxical enhancement of oxidative stress and unbalanced cellular redox potential. Overdosing on particular antioxidants has been associated with increased medication interactions, cancer progression, and fatality risks. Additionally, the complex impacts they may have on fertility might be both useful and adverse, depending on the quantity and duration of usage. This review delves into the dual role of antioxidants and emphasizes the importance of employing antioxidants in moderation. Antioxidant overconsumption may disrupt the oxidative balance necessary for normal sperm and oocyte function, which is one of the potential negative effects of antioxidants on fertility in both males and females that are also investigated. Although modest usage of antioxidants is generally safe and useful, high levels of antioxidants can upset hormonal balance, impair sperm motility, and negatively impact the outcomes of assisted reproductive technologies (ART). The findings emphasize the need to use antioxidant supplements in a balanced way, the importance of further research to optimize their use in fertility treatments, and the importance of supporting reproductive health to avoid adverse effects. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress and Antioxidants in Human Disease)

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