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Molecules and Mechanisms of Oxidative Stress Relevant in the Pathophysiology of Diseases

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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 April 2026 | Viewed by 8086

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Special Issue Editor

Dr. Cinzia Signorini

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Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy
Interests: isoprostanes; neuroprostanes; markers of oxidative stress; oxidative stress in human diseases
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Special Issue Information

Dear Colleagues,

As an imbalance in redox signalling, oxidative stress can negatively affect biological molecules and functions. Pathophysiology, as a response to biological and functional damage, involves the mechanisms underlying diseases because of alterations in cells, tissues, and organs.

Here, we will study the involvement of oxidative stress in driving the processes that lead to disease manifestation, homeostatic responses to disease, and disease progression.

We welcome contributions related to the pro-oxidant action of iron and/or oxygen, reactive oxygen species, antioxidants, inflammation, human disease, cell injury, and oxidative damage.

Dr. Cinzia Signorini
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 submissions that pass pre-check are 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 250 words) can be sent to the Editorial Office for assessment.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

redox-active iron
reactive oxygen species
antioxidants
oxidative damage
biomarkers
degenerative disease

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Published Papers (6 papers)

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Research

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18 pages, 4145 KB

Open AccessArticle

Significant Suppression of Multiple Sclerosis in the Mouse EAE Model Using the PrC-210 Aminothiol

by William E. Fahl, Bryan L. Fahl, Sarah R. Goesch, Hannah R. Goesch and Torsten R. Goesch

Int. J. Mol. Sci. 2025, 26(21), 10597; https://doi.org/10.3390/ijms262110597 - 30 Oct 2025

Viewed by 422

Abstract

Multiple sclerosis (MS) is a complex disease marked by chronic neuroinflammation and reactive oxygen species (ROS) toxicity in the central nervous system (CNS). Based on this ROS-driven mechanism, we tested whether PrC-210—a new aminothiol ROS scavenger—could lessen MS symptoms in mice with experimental autoimmune encephalomyelitis (EAE)-induced MS. Our goals were to assess the role of ROS in MS and evaluate the potential benefits of PrC-210 for managing MS. Mice with EAE received varying doses of PrC-210 under preventive and therapeutic protocols. Disease progression was measured using clinical scores and spinal cord histology. Safety was assessed by comparing the gastrointestinal and hematological toxicity between PrC-210 and dimethyl fumarate (DMF, Tecfidera’s active agent). PrC-210 reduced MS severity by up to 62% in paralysis scores versus those in the controls (p = 0.0001), whether used preventively or at the onset of paralysis. The group with the greatest decrease also showed the best spinal cord preservation and least demyelination. DMF caused toxicity at a dose that was ineffective, while PrC-210 showed no toxicity at effective levels. These findings suggest that the systemic administration of PrC-210 may offer a safe, effective MS treatment when started at symptom onset. Full article

(This article belongs to the Special Issue Molecules and Mechanisms of Oxidative Stress Relevant in the Pathophysiology of Diseases)

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24 pages, 11368 KB

Open AccessArticle

Co-Supplementation of Policosanol and Banaba Leaf Extract Exhibited a Cooperative Effect Against Hyperglycemia and Dyslipidemia in Zebrafish: Highlighting Vital Organ Protection Against High-Cholesterol and High-Galactose Diet

by Kyung-Hyun Cho, Sang Hyuk Lee, Yunki Lee, Ashutosh Bahuguna, Ji-Eun Kim and Cheolmin Jeon

Int. J. Mol. Sci. 2025, 26(16), 7669; https://doi.org/10.3390/ijms26167669 - 8 Aug 2025

Viewed by 2001

Abstract

The efficacy of Lagerstroemia speciosa (banaba) leaf extract (BLE), policosanol (POL), and their combination (BLE+POL) was evaluated in zebrafish (Danio rerio) against high cholesterol (HC)- and galactose (HG)-induced metabolic stress and organ toxicity. After 12 weeks of dietary intervention, BLE+POL significantly reduced HC+HG-augmented weight gain and improved hepatic and nephromegaly. Compared with BLE or POL alone, the combined intake of BLE+POL more effectively alleviated dyslipidemia and blood glucose levels. Likewise, BLE+POL effectively reduced blood malondialdehyde (MDA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and boosted plasma sulfhydryl content, ferric ion reduction ability (FRA), and paraoxonase (PON) activity. Histological outcomes suggest that BLE+POL has higher efficacy than either BLE or POL in mitigating HC+HG-induced fatty liver changes, hepatic inflammation, kidney senescence, and reactive oxygen species (ROS) production. Consistently, BLE+POL augmented the spermatozoa counts in the testes, enhanced mature vitellogenic oocytes in ovaries, and protected them from the HC+HG-induced oxidative stress. Compared with either BLE or POL, a combined intake of BLE+POL displayed a superior effect in inhibiting the apoptosis and accumulation of lipid peroxidation species 4-hyrdoxynonenal (4-HNE) in the brain. A combined intake of BLE+POL exhibited a pronounced impact than the BLE and POL alone and can be utilized as an effective formulation to counteract the HC+HG-induced events. Full article

(This article belongs to the Special Issue Molecules and Mechanisms of Oxidative Stress Relevant in the Pathophysiology of Diseases)

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11 pages, 769 KB

Open AccessArticle

Sperm Motility Is Modulated by F₄-Neuroprostane via the Involvement of Ryanodine Receptors

by Cinzia Signorini, Elena Moretti, Laura Liguori, Caterina Marcucci, Thierry Durand, Jean-Marie Galano, Camille Oger and Giulia Collodel

Int. J. Mol. Sci. 2025, 26(15), 7231; https://doi.org/10.3390/ijms26157231 - 26 Jul 2025

Viewed by 2750

Abstract

F₄-Neuroprostanes (F₄-NeuroPs), oxidative metabolites of docosahexaenoic acid, act as bioactive lipid mediators enhancing sperm motility and induce capacitation-like changes in vitro. Their biological action is proposed to involve sperm ion channels, in particular ryanodine receptors (RyRs), which regulate intracellular calcium homeostasis. We evaluated the effects of dantrolene, a RyR inhibitor, on motility and vitality of a selected spermatozoa at different concentrations (10, 30, 50, 100 μM). Then sperm motility, acrosome integrity, and RyR localization following co-incubation with dantrolene (D50 or D100 μM) and 4-/10-F_4t-NeuroPs (7 ng) were investigated. Acrosomal status was assessed using Pisum sativum agglutinin (PSA) staining and RyR localization by immunofluorescence. D50 was identified as the minimum effective dose to induce significant reductions in sperm motility. F₄-NeuroPs significantly increased rapid progressive motility versus controls. Co-incubation with F₄-NeuroPs + D50 reduced rapid motility and increased in situ and circular movement. The acrosome staining appeared altered or absent to different percentages, and RyR localization was also seen in the midpiece. These findings suggested that F₄-NeuroPs enhance sperm motility via RyR-mediated pathways, as confirmed by dantrolene inhibition. Accordingly, our results underscore the physiological relevance of RyRs in sperm function and suggest new insights into lipid-based mechanisms regulating sperm motility. Full article

(This article belongs to the Special Issue Molecules and Mechanisms of Oxidative Stress Relevant in the Pathophysiology of Diseases)

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Review

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23 pages, 843 KB

Open AccessReview

Exploring the Potential of Molecular Hydrogen in Different Heart Failure Models: A Review

by Daria Kornieieva, Barbora Kalocayova, Jan Slezak and Branislav Kura

Int. J. Mol. Sci. 2025, 26(23), 11574; https://doi.org/10.3390/ijms262311574 - 28 Nov 2025

Viewed by 429

Abstract

Heart failure (HF) is increasing in prevalence in many countries around the world. HF is a complex clinical syndrome characterized by the heart’s inability to pump blood effectively, resulting in significant morbidity and mortality. After an initial cardiac event (e.g., myocardial infarction, valve dysfunction, hypertension, etc.), adaptive mechanisms are activated to preserve cardiac function. Sustained activation of these mechanisms leads to cellular and structural changes involving cardiac remodeling and hypertrophy. This ultimately leads to impaired cardiac contractility and reduced cardiac output, with a 5-year HF-associated mortality rate up to 75%. The current treatment strategies for HF are not sufficient to cover all the underlying complex mechanisms. It has been demonstrated that molecular hydrogen (H₂) exerts cardioprotective effects via its antioxidant, anti-inflammatory, and anti-apoptotic action. The number of studies exploring beneficial effects of H₂ in different HF models is increasing. This is the first review summarizing the knowledge in this field. The available literature indicates that H₂ may be effective in mitigating different HF pathologies via regulating cardiac oxidative stress and inflammation, cardiomyocyte death, and mitochondrial function/cell metabolism, as well as cardiac remodeling, including hypertrophy and fibrosis. As this area of research is still in its infancy, the feasibility and efficiency of H₂ treatment in different HF types need further investigation. Full article

(This article belongs to the Special Issue Molecules and Mechanisms of Oxidative Stress Relevant in the Pathophysiology of Diseases)

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17 pages, 2069 KB

Open AccessReview

Salivary Oxidative Stress Biomarkers in Peri-Implant Disease: A Systematic Review and Meta-Analysis

by Paul Șerban Popa, Gabriel Valeriu Popa, Kamel Earar, Claudia Elisabeta Popa-Cazacu and Mădălina Nicoleta Matei

Int. J. Mol. Sci. 2025, 26(23), 11269; https://doi.org/10.3390/ijms262311269 - 21 Nov 2025

Viewed by 290

Abstract

Peri-implantitis, a common biological complication of dental implants, is characterized by soft-tissue inflammation and progressive bone loss. Oxidative stress is increasingly implicated in its pathogenesis, yet the diagnostic potential of salivary redox biomarkers remains unclear. This study’s objective was to assess the association between salivary malondialdehyde (MDA) and total antioxidant capacity (TAC) and peri-implant disease via a pre-registered, quantitative meta-analysis of previously published studies using predefined statistical criteria. Following a priori PROSPERO registration, we systematically searched PubMed, Scopus, and Web of Science (2004–September 2025), extracted data in duplicate, and pooled effects using random-effects models; certainty of evidence was appraised with GRADE (Grading of Recommendations Assessment, Development and Evaluation) and risk of bias with ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions)/QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). Twelve studies were included qualitatively: seven (n = 726) contributed to MDA and five (n = 485) to TAC meta-analyses. Peri-implant disease was associated with elevated MDA (SMD = 1.64, 95% CI 1.39–1.88) and reduced TAC (SMD = −1.88, 95% CI −2.17 to −1.58); statistical heterogeneity was not detected, and results were robust to sensitivity and exploratory assay-based subgroup analyses. Salivary MDA and TAC show consistent, large, standardized differences in peri-implant disease; however, observational designs, assay variability, and the absence of validated diagnostic thresholds warrant cautious interpretation and prospective validation before clinical adoption. Full article

(This article belongs to the Special Issue Molecules and Mechanisms of Oxidative Stress Relevant in the Pathophysiology of Diseases)

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29 pages, 802 KB

Open AccessReview

Endometrial Microbiome and Reproductive Receptivity: Diverse Perspectives

by Galina Stoyancheva, Nikolina Mihaylova, Maria Gerginova and Ekaterina Krumova

Int. J. Mol. Sci. 2025, 26(21), 10796; https://doi.org/10.3390/ijms262110796 - 6 Nov 2025

Viewed by 1675

Abstract

The human endometrium, previously considered a sterile environment, is now recognized as a low-biomass but biologically active microbial niche critical to reproductive health. Advances in sequencing technologies, particularly shotgun metagenomics, have provided unprecedented insights into the taxonomic and functional complexity of the endometrial microbiome. While 16S rRNA sequencing has delineated the distinction between Lactobacillus-dominant and non-dominant microbial communities, shotgun metagenomics has revealed additional diversity at the species and strain level, uncovering microbial signatures that remain undetected by amplicon-based approaches. Current evidence supports the association of Lactobacillus dominance with endometrial homeostasis and favorable reproductive outcomes. Dysbiosis, characterized by increased microbial diversity and enrichment of anaerobic taxa such as Gardnerella, Atopobium, Prevotella, and Streptococcus, is linked to chronic endometritis, implantation failure, and adverse IVF results. Beyond compositional differences, the endometrial microbiome interacts with the host through immunological, metabolic, and epigenetic mechanisms. These interactions modulate cytokine signaling, epithelial barrier integrity, and receptivity-associated gene expression, ultimately influencing embryo implantation. However, discrepancies between published studies reflect the lack of standardized protocols for sampling, DNA extraction, and bioinformatic analysis, as well as the inherent challenges of studying low-biomass environments. Factors such as geography, ethnicity, hormonal status, and antibiotic exposure further contribute to interindividual variability. Culturomics approaches complement sequencing by enabling the isolation of viable bacterial strains, offering perspectives for microbiome-based biotherapeutics. Emerging 3D endometrial models provide additional tools to dissect microbiome–host interactions under controlled conditions. Taken together, the growing body of data highlights the potential of endometrial microbiome profiling as a biomarker for reproductive success and as a target for personalized interventions. Future research should focus on integrating multi-omics approaches and functional analyses to establish causal relationships and translate findings into clinical practice. This review gives a new insight into current knowledge on the uterine microbiome and its impact on implantation success, analyzed through the lenses of microbiology, immunology, and oxidative stress. Full article

(This article belongs to the Special Issue Molecules and Mechanisms of Oxidative Stress Relevant in the Pathophysiology of Diseases)

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