Exploring New Frontiers in Oxidative Stress and Antioxidant Research: From Model Organisms to Human 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: 31 July 2026 | Viewed by 5048

Special Issue Editors


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Guest Editor
New York Genome Center, New York, NY 10013, USA
Interests: developmental genetics; genomics; mitochondria; cell signaling

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Guest Editor
1. Department of Medicine, Albert Einstein College of Medicine, New York City, NY 10461, USA
2. Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York City, NY 10461, USA
Interests: cardiology; hypertension; restenosis; heart failure; myocardial infarction; endothelial dysfunction; mitochondria; diabetes; microRNAs; insulin resistance; atherosclerosis; thrombosis; cardiac hypertrophy; pancreatic beta cell function; insulin release
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Special Issue Information

Dear Colleagues,

Oxidative stress plays a critical role in the pathogenesis of numerous human diseases, including cancer, neurological disorders, cardiometabolic conditions, and aging. Understanding the intricate mechanisms regulating oxidative stress and the homeostatic antioxidant response is essential for developing innovative therapeutic interventions.

Insights gained from model organisms offer valuable perspectives on the molecular and cellular processes underlying oxidative stress, paving the way for novel translational approaches in human disease research. This Special Issue aims to highlight recent advancements in oxidative stress and antioxidant research using model organisms with direct relevance to human health.

We welcome contributions focusing on cellular processes such as cell cycle regulation, intercellular communication, and cell death—key pathways implicated in disease progression. Special emphasis will be placed on studies employing cutting-edge, high-throughput omics technologies, including transcriptomics, single-cell genomics, metabolomics, and proteomics. Additionally, novel strategies for the targeted delivery of antioxidant-based therapies will be of particular interest.

By integrating findings from diverse model systems, this Special Issue seeks to foster a deeper understanding of oxidative stress-related pathophysiology and drive the development of effective therapeutic strategies for human diseases.

Dr. Marcello Ziosi
Dr. Gaetano Santulli
Guest Editors

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Keywords

  • oxidative stress
  • antioxidant therapeutics
  • cell death and survival pathways
  • cellular signaling networks
  • gene regulation and expression

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Published Papers (3 papers)

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Review

31 pages, 1457 KB  
Review
Ferroptosis in Human Diseases: Fundamental Roles and Emerging Therapeutic Perspectives
by Ilaria Artusi, Michela Rubin, Giovanni Cravin and Giorgio Cozza
Antioxidants 2025, 14(12), 1411; https://doi.org/10.3390/antiox14121411 - 26 Nov 2025
Viewed by 657
Abstract
Ferroptosis is a novel iron-sensitive subtype of regulated cell death (RCD), persisting under extreme lipid peroxidation and iron/redox imbalances. Unlike apoptosis, necroptosis, and pyroptosis, ferroptosis is a signaling-driven process mediated through iron metabolism imbalance, polyunsaturated fatty acid (PUFA) exceeding oxidation, and defects in [...] Read more.
Ferroptosis is a novel iron-sensitive subtype of regulated cell death (RCD), persisting under extreme lipid peroxidation and iron/redox imbalances. Unlike apoptosis, necroptosis, and pyroptosis, ferroptosis is a signaling-driven process mediated through iron metabolism imbalance, polyunsaturated fatty acid (PUFA) exceeding oxidation, and defects in its protective systems like Xc-/GSH/GPx4. Specifically, this review establishes that iron-driven ferroptosis is a central underlying pathomechanistic factor in a broad range of human diseases. Significantly, whether its modulation is therapeutic, it is entirely conditional on the specific disease context. Thus, its induction can provide a promising antidote for destructive cancer cells when conjoined with immuno-therapies to boost anticancer immunity. Conversely, iron-mediated ferroptosis suppression is a key factor in countering destructive changes in a whole range of degenerative and acute injuries. Current therapeutic approaches include iron chelators, lipid oxidation inhibitors, GPx4 activators, natural and active compounds, and novel drug delivery systems. However, against all odds and despite its intense therapeutic promise, its translation into a practical medicinal strategy faces many difficulties. Thus, a therapeutic agent specifically focused on its modulation is still lacking. The availability of selective biologic markers is a concern. The challenges in the direct pathologic identification of ferroptosis in a complex in vivo systemic scenario remain. Current avenues for its future development are pathogen infections, the discovery of novel regulating factors, and novel approaches to personalized medicine centered on its organ-level in vivo signatures. Full article
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18 pages, 1837 KB  
Review
Emerging and Versatile Non-Mammalian Model Organisms for Studying the In Vivo Antioxidant Properties of Food-Derived Bioactive Compounds
by Alejandra Miranda-Carrazco, Verenice Torres-Salas, Rosy G. Cruz-Monterrosa, Monzerrat Rosas-Espejel, Ildefonso Guerrero-Encinas, Javier N. González-González, Luis Quihui-Cota, Andrea M. Liceaga and José E. Aguilar-Toalá
Antioxidants 2025, 14(9), 1127; https://doi.org/10.3390/antiox14091127 - 18 Sep 2025
Cited by 1 | Viewed by 866
Abstract
In recent years, there has been increased attention to exploring non-mammalian model organisms to study the antioxidant properties of bioactive compounds. These models include both unicellular organisms, such as Escherichia coli and Saccharomyces cerevisiae, and multicellular organisms, such as Caenorhabditis elegans, Drosophila [...] Read more.
In recent years, there has been increased attention to exploring non-mammalian model organisms to study the antioxidant properties of bioactive compounds. These models include both unicellular organisms, such as Escherichia coli and Saccharomyces cerevisiae, and multicellular organisms, such as Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio. In particular, multicellular models have emerged as promising systems due to their ease of establishing systems and maintenance, short duration of experiments, ease of genetic manipulation and genome-wide screening, availability as off-the-shelf models, safety, and cost-effectiveness. Notably, these organisms share a high degree of gene homology with humans, ranging from 65% to 84%, which positions them as powerful platforms for investigating human disease mechanisms. These advantages make them attractive candidates for investigating the potential health benefits of various bioactive compounds before resorting to mammalian models. This review delves into the rationale for utilizing these emerging non-mammalian model organisms during preliminary stages of research, emphasizing their distinct advantages over traditional mammalian models. It also highlights their significant contributions to advancing our understanding of the antioxidant mechanisms of bioactive compounds, shedding light on their potential therapeutic implications for human health. By leveraging these models, researchers can efficiently screen and validate bioactive compounds, laying a robust foundation for subsequent translational studies in mammalian systems. Full article
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36 pages, 757 KB  
Review
Oxidative Stress in the Pathophysiology of Chronic Venous Disease: An Overview
by Sonia Rațiu, Mihaela I. Mariș, Adina V. Furdui-Lința, Laurențiu V. Sima, Tiberiu I. Bratu, Adrian Sturza, Danina M. Muntean and Octavian M. Crețu
Antioxidants 2025, 14(8), 989; https://doi.org/10.3390/antiox14080989 - 12 Aug 2025
Cited by 3 | Viewed by 2926
Abstract
Chronic venous disease (CVD) and its major manifestation, varicose veins (VV) of the lower limbs, is a common, multifactorial disease that affects a significant percentage of adult and elderly people worldwide. Its prevalence has been constantly increasing with the aging of the population [...] Read more.
Chronic venous disease (CVD) and its major manifestation, varicose veins (VV) of the lower limbs, is a common, multifactorial disease that affects a significant percentage of adult and elderly people worldwide. Its prevalence has been constantly increasing with the aging of the population and, particularly, with the obesity pandemic (hence, the term ‘phlebesity’). The major pathophysiological mechanisms that are potentiating each other in a vicious cycle, leading to chronic venous hypertension, are represented by endothelial dysfunction, chronic inflammation, impaired hemodynamics, and venous wall remodeling. Oxidative stress is another pathomechanism responsible for CVD and its complications, with the increased generation of reactive oxygen species and decreased antioxidant defense being reported to contribute to VV formation. Herein, we present evidence for the role of impaired redox homeostasis as pathophysiological mechanism responsible for chronic local and systemic oxidative stress in patients with CVD. Full article
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