Antioxidants

36 pages, 757 KiB

Open AccessReview

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 (registering DOI) - 12 Aug 2025

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

(This article belongs to the Special Issue Exploring New Frontiers in Oxidative Stress and Antioxidant Research: From Model Organisms to Human Disease)

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14 pages, 795 KiB

Open AccessCommunication

Effect of Vitamin C on the Antioxidant and Immune Response of Male White Shrimp (Penaeus vannamei) Broodstock

by Grecia Montalvo, Sarabí Caballeros, Karla Escalante, Alvaro Barreto, Martín Arenas and Gabriela Gaxiola

Antioxidants 2025, 14(8), 988; https://doi.org/10.3390/antiox14080988 (registering DOI) - 12 Aug 2025

Abstract

This study evaluated the effect of vitamin C (L-ascorbyl-2-polyphosphate) on the physiological condition, biochemical antioxidant activity, immune responses, and gene expression in the reproductive tract, as well as on sperm quantity and quality in male white shrimp Penaeus vannamei broodstock. Four diets containing [...] Read more.

This study evaluated the effect of vitamin C (L-ascorbyl-2-polyphosphate) on the physiological condition, biochemical antioxidant activity, immune responses, and gene expression in the reproductive tract, as well as on sperm quantity and quality in male white shrimp Penaeus vannamei broodstock. Four diets containing 42.5% protein, 11.5% lipids, and 23.5% carbohydrates were formulated with L-ascorbyl-2-polyphosphate as a source of vitamin C at the following concentrations: 0.016 g/kg (Basal), 0.322 g/kg (A), 0.628 g/kg (B), and 0.934 g/kg (C). Shrimp fed diet C exhibited the highest SOD and CAT activity and serum cholesterol levels, but the lowest expression of hemocyanin (Hemo) mRNA transcripts (p ˂ 0.05). Shrimp fed diet A showed the highest Hemo mRNA expression and phenoloxidase (PO) activity, while those fed diet B had the highest serum triglyceride levels (p ˂ 0.05). In contrast, shrimp fed diets A and B exhibited the lowest serum cholesterol levels (p ˂ 0.05). There were no differences in sperm quality between the diets. In relation to sperm quantity, the shrimp fed diet B had the highest sperm cell count (2,750,000 cel/mL), and those fed diet A had the lowest (585,000 cel/mL) (p ˂ 0.05). These results indicate that vitamin C influences the reproductive aspects of male P. vannamei broodstock. A dietary inclusion level of 0.628 g/kg promotes optimal physiological, oxidative stress, and immunological conditions for increased sperm cell production, whereas an excessive level may promote oxidative stress. Full article

(This article belongs to the Special Issue Antioxidant Response in Aquatic Animals)

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39 pages, 4384 KiB

Open AccessReview

Oxidative Stress-Driven Cellular Senescence: Mechanistic Crosstalk and Therapeutic Horizons

by Bojan Stojanovic, Ivan Jovanovic, Milica Dimitrijevic Stojanovic, Bojana S. Stojanovic, Vojin Kovacevic, Ivan Radosavljevic, Danijela Jovanovic, Marina Miletic Kovacevic, Nenad Zornic, Ana Azanjac Arsic, Stevan Eric, Nikola Mirkovic, Jelena Nesic, Stefan Jakovljevic, Snezana Lazarevic, Ivana Milivojcevic Bevc and Bojan Milosevic

Antioxidants 2025, 14(8), 987; https://doi.org/10.3390/antiox14080987 (registering DOI) - 12 Aug 2025

Abstract

Cellular senescence, a state of permanent cell cycle arrest, represents a double-edged sword in biology—providing tumor-suppressive functions while contributing to tissue degeneration, chronic inflammation, and age-related diseases when senescent cells persist. A key driver of senescence is oxidative stress, primarily mediated by excessive [...] Read more.

Cellular senescence, a state of permanent cell cycle arrest, represents a double-edged sword in biology—providing tumor-suppressive functions while contributing to tissue degeneration, chronic inflammation, and age-related diseases when senescent cells persist. A key driver of senescence is oxidative stress, primarily mediated by excessive reactive oxygen species that damage mitochondrial DNA, modulate redox-sensitive signaling pathways, and trigger the senescence-associated secretory phenotype. Emerging evidence highlights the pathogenic role of SASP in promoting local inflammation, immune evasion, and senescence propagation. This review explores the intricate interplay between redox imbalance and cellular senescence, emphasizing mitochondrial dysfunction, SASP dynamics, and their implications in aging and cancer. We discuss current senotherapeutic strategies—including senolytics, senomorphics, antioxidants, gene therapy, and immunotherapy—that aim to eliminate or modulate senescent cells to restore tissue homeostasis. Understanding the heterogeneity and context-specific behavior of senescent cells remains crucial for optimizing these therapies. Future research should focus on addressing key knowledge gaps, including the standardization of senescence biomarkers such as circulating miRNAs, refinement of predictive preclinical models, and development of composite clinical endpoints. These efforts are essential to translate mechanistic insights into effective senotherapeutic interventions and enable the safe integration of senescence-targeting strategies into routine clinical practice. Full article

(This article belongs to the Special Issue Oxidative Stress in Cell Senescence)

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17 pages, 1841 KiB

Open AccessReview

An Update on Role of Ionizing Radiation to Enhance Proliferation and Differentiation of Normal Stem Cells via Activation of NRF2 Pathway: Review

by Kave Moloudi and Siamak Haghdoost

Antioxidants 2025, 14(8), 986; https://doi.org/10.3390/antiox14080986 - 11 Aug 2025

Abstract

Ionizing radiation (IR) as a stress inducer has a significant impact on various normal stem cells differentiation through activation of various signaling pathways. Low levels of oxidative stress of IR may preserve or even enhance cell differentiation. In response to IR, reactive oxygen [...] Read more.

Ionizing radiation (IR) as a stress inducer has a significant impact on various normal stem cells differentiation through activation of various signaling pathways. Low levels of oxidative stress of IR may preserve or even enhance cell differentiation. In response to IR, reactive oxygen species (ROS) can activate various signaling pathways that promote cell differentiation, notably through the involvement of nuclear factor erythroid 2–related factor 2 (NRF2). NRF2 interacts with multiple pathways, including Wnt/β-catenin (osteogenesis), PPARγ (adipogenesis), and BDNF/TrkB (neurogenesis). This response is dose-dependent: low doses of IR activate NRF2 and support differentiation, while high doses can overwhelm the antioxidant system, resulting in cell death. However, the quality of various types of IR, such as proton and carbon ion radiation, may have a varied impact on stem cells (SCs) differentiation compared to X-rays. Hence, activation of the NRF2 signaling pathway in SCs and cell differentiation depends on the level of stress and the quality and quantity of IR. This review is an update to explore how IR modulates SCs fate toward osteogenic, adipogenic, and neurogenic lineages through the NRF2 signaling pathway. We highlight mechanistic insights, dose-dependent effects, and therapeutic implications, bridging gaps between experimental models and clinical translation. Full article

(This article belongs to the Special Issue Oxidative Stress and NRF2 in Health and Disease—2nd Edition)

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Graphical abstract

36 pages, 4124 KiB

Open AccessArticle

Past and Present of the Antioxidant Studies in Chile: A Bibliometric Study from 2000 to 2024

by Marcos Lorca, Alejandro Vega-Muñoz, Alison Acosta, David Cabezas, Katy Díaz, Jaime Mella, Gianfranco Sabadini, Guido Salazar-Sepúlveda, Nicolás Contreras-Barraza and Marco Mellado

Antioxidants 2025, 14(8), 985; https://doi.org/10.3390/antiox14080985 - 11 Aug 2025

Abstract

Since 2000, antioxidant research in Chile has shown steady growth, from the chemical sciences to their application in biomedical sciences, functional foods, reproduction, and environmental studies. This study presents a bibliometric analysis of Chilean scientific output in the field of antioxidants from 2000 [...] Read more.

Since 2000, antioxidant research in Chile has shown steady growth, from the chemical sciences to their application in biomedical sciences, functional foods, reproduction, and environmental studies. This study presents a bibliometric analysis of Chilean scientific output in the field of antioxidants from 2000 to 2024, organized into five-year intervals. A total of 3190 research articles indexed in the Web of Science (WoS) database were analyzed. Bibliometric indicators—including Price’s, Bradford’s, and Zipf’s laws—were applied to assess literature growth, authorship concentration, journal dispersion, and keyword evolution. Key findings include (i) high productivity from institutions such as the Universidad de Chile, Pontificia Universidad Católica de Chile, Universidad de Santiago de Chile, and Universidad de Concepción; (ii) the identification of leading authors such as Dr. Antonio Vega-Gálvez, Dr. Guillermo Schmeda-Hirschman, and Dr. Mario J. Simirgiotis; and (iii) the consolidation of three main research areas: biomedical applications (e.g., cancer, cardiovascular, and neurodegenerative diseases), food science and technology (e.g., antioxidant properties, and agro-industrial waste revalorization), and ethnopharmacology (e.g., native plant use). This study made it possible to map the state of the art of antioxidant research in Chile and identify key players and research lines, consolidating a comprehensive vision of scientific development in this field. Full article

(This article belongs to the Special Issue Antioxidant Research in Chile—2nd Edition)

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24 pages, 5689 KiB

Open AccessArticle

Impaired Renal Function Due to Reductive Stress Is Associated with Excessive Consumption of Hibiscus sabdariffa Linnaeus

by Linaloe Manzano-Pech, María Elena Soto, Vicente Castrejón-Tellez, Verónica Guarner-Lans, Alan Axel Pérez-Flores, Sara Caballero-Chacón, Raúl Martínez-Memije, María Esther Rubio-Ruiz, Félix Leao Rodríguez-Fierros, Juan Carlos Torres-Narváez, Luz Ibarra-Lara and Israel Pérez-Torres

Antioxidants 2025, 14(8), 984; https://doi.org/10.3390/antiox14080984 - 11 Aug 2025

Abstract

Reductive stress (RS) results from the overactivity of the enzymatic and non-enzymatic antioxidant systems and from excess antioxidant agents that neutralize reactive oxygen species. Hibiscus sabdariffa Linnaeus (HSL) is a natural source of antioxidant molecules that can overload the antioxidant system. Twenty-one Wistar [...] Read more.

Reductive stress (RS) results from the overactivity of the enzymatic and non-enzymatic antioxidant systems and from excess antioxidant agents that neutralize reactive oxygen species. Hibiscus sabdariffa Linnaeus (HSL) is a natural source of antioxidant molecules that can overload the antioxidant system. Twenty-one Wistar rats were divided into three groups: group 1 (G) G1: rats that consumed a 6% HSL infusion for one month (HSL + 6%), G2: rats that consumed a 6% HSL infusion for one month and were then given natural water for another month (HSL ± 6%), and G3: rats with natural drinking water. Renal vascular resistance (RVR) was evaluated through their responses to norepinephrine (Ne), acetylcholine (Ach), super oxide (O₂⁻), hydrogen peroxide (H₂O₂)_, and peroxynitrite (ONOO⁻). The activity of antioxidant enzymes and oxidative stress markers was evaluated. RVR was increased by Ne and H₂O₂ (p = 0.03), but it was decreased by Ach, O₂⁻, and ONOO⁻ (p = 0.01). The reduced glutathione / oxidized glutathione (GSH/GSSG) ratio and nitrates/nitrites ratio, the total antioxidant capacity, the activities of superoxide dismutase, catalase, peroxidases, glutathione peroxidase, glutathione reductase, glucose-6-phosphate, and the expression of phosphorylated NrF2 were increased (p ≤ 0.04). However, the thiol groups, adenochrome, and glutathione-S-transferase were decreased (p = 0.01) in G1 vs. G2 and G3. The excessive consumption of antioxidants provided by a 6% HSL infusion results in RS contributing to a decrease in ROS. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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19 pages, 2452 KiB

Open AccessArticle

Development and In Vitro Cytotoxicity Evaluation of Individual and Combined Injectable Solutions of Curcumin and Resveratrol Against Lung Cancer Cells

by Ximena Hernández Martínez, Carla O. Contreras-Ochoa, Marisol Mir-Garcia, Nataly Aguilar-García, Hugo Cortés Martínez, Elvia A. Morales-Hipólito, Sandra L. Hernández-Ojeda, Mariana Dolores-Hernández, Bruno Solis-Cruz, J. J. Espinosa-Aguirre, Daniel Hernandez-Patlan and Raquel López-Arellano

Antioxidants 2025, 14(8), 983; https://doi.org/10.3390/antiox14080983 - 11 Aug 2025

Abstract

The objective of the present study was to develop injectable solutions of curcumin (CUR) and resveratrol (RES) for intravenous administration as a strategy to increase their solubility and stability, as well as to evaluate their cytotoxic potential, individually and in combination, on human [...] Read more.

The objective of the present study was to develop injectable solutions of curcumin (CUR) and resveratrol (RES) for intravenous administration as a strategy to increase their solubility and stability, as well as to evaluate their cytotoxic potential, individually and in combination, on human lung non-small adenocarcinoma cells (A549 cells) and non-tumoral cells isolated from normal human bronchial epithelium (BEAS cells) to establish possible synergistic effects and potential therapeutic alternatives for lung cancer. Using factorial experimental designs, the components of the injectable CUR and RES solutions were selected, and their hemolytic potential was evaluated by a static method. In addition, combinations of injectable CUR:RES solutions (25:75, 50:50 and 75:25) were prepared from the individual ones, and their stability under refrigeration conditions and cytotoxic potential on A549 and BEAS cells were evaluated. The stability of the injectable solutions of CUR, RES and their different combinations was maintained for 3 months, except for the 25:75 combination of CUR:RES. Furthermore, the cytotoxic potential of CUR and RES on tumoral cells (A549) and non-tumoral (BEAS) cells was evaluated, indicating a dose-dependent effect; the combination of CUR:RES 50:50 and the combination of CUR:RES 75:25 presented synergistic effects in reducing cell viability. This study suggests that injectable solutions of CUR, RES and their combination for intravenous administration could be potential viable candidates and should be evaluated for their efficacy in animal models of lung cancer to establish new possible treatments. Full article

(This article belongs to the Special Issue Novel Approaches in Natural Occuring Antioxidants in the Prevention and Treatment of Chronic Diseases, 2nd Edition)

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46 pages, 3268 KiB

Open AccessReview

New Approaches and Strategies for the Repurposing of Iron Chelating/Antioxidant Drugs for Diseases of Free Radical Pathology in Medicine

by George J. Kontoghiorghes

Antioxidants 2025, 14(8), 982; https://doi.org/10.3390/antiox14080982 - 10 Aug 2025

Abstract

There is an urgent need for new approaches and strategies for the introduction of antioxidant drugs in medicine. Despite hundreds of clinical trials with potential antioxidants, no antioxidant drugs have so far been developed for clinical use; this is mainly as a result [...] Read more.

There is an urgent need for new approaches and strategies for the introduction of antioxidant drugs in medicine. Despite hundreds of clinical trials with potential antioxidants, no antioxidant drugs have so far been developed for clinical use; this is mainly as a result of commercial reasons, but also due to insufficient data for regulatory authority approval. Antioxidant activity is a physiological process essential for healthy living. However, increased production of toxic free radicals and reactive oxygen species is observed in many clinical conditions, which are associated with serious and sometimes irreversible damage. Antioxidant drug strategies may involve short- to long-term therapeutic applications for the purpose of prevention, treatment, or post-treatment effects of a disease. These strategies are different for each disease and may include the design of protocols for the inhibition of oxidative damage through iron chelation, enhancing antioxidant defences by increasing the production of endogenous antioxidants, and activating antioxidant mechanisms, as well as the administration of synthetic and natural antioxidants. Both the improvement of antioxidant biomarkers and clinical improvement or disease remission are required to suggest effective therapeutic intervention. More concerted efforts, including new academic strategies, are required for the development of antioxidant drugs in clinical practice. Such efforts should be similar to the fulfilment of orphan or emergency drug regulatory requirements, which, in most cases, involve the treatment or clinical improvement of rare or severe diseases such as neurodegenerative diseases and cancer. Promising results of antioxidant therapeutic interventions include mainly the repurposing of the iron chelating/antioxidants drugs deferiprone (L1) and deferoxamine, and also the iron-binding drug N-acetylcysteine (NAC). In some clinical trials, the lack of pharmacodynamic and ferrikinetic data, wrong posology, and insufficient monitoring have resulted in inconclusive findings. Future strategies involving appropriate protocols and drug combinations, such as L1 and NAC, appear to improve the prospect of developing antioxidant drug therapies in different diseases, including those associated with ferroptosis. New strategies may also involve the use of pro-drugs such as aspirin, which is partly biotransformed into iron chelating/antioxidant metabolites with chemopreventive properties in cancer, and also in other therapeutic interventions. A consortium of expert academics on regulatory drug affairs and clinical trials could increase the prospects for antioxidant drug development in medicine. Full article

(This article belongs to the Section ROS, RNS and RSS)

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31 pages, 21567 KiB

Open AccessArticle

Synergistic Effects of Antioxidant Blends: A Comparative Study on Oxidative Stability of Lipids in Feed Matrices

by Xuyang Gao, Yong Xiao, Wen Li, Liting Xu and Jianmin Yuan

Antioxidants 2025, 14(8), 981; https://doi.org/10.3390/antiox14080981 - 10 Aug 2025

Abstract

Lipid peroxidation driven by polyunsaturated fatty acid (PUFA) oxidation compromises feed quality and animal health. Single antioxidants (e.g., ethoxyquin (EQ), butylated hydroxytoluene (BHT)) face limitations including dose-dependent toxicity, bioaccumulation risks, and inadequate protection against multistage oxidation. Composite systems leveraging complementary mechanisms offer a [...] Read more.

Lipid peroxidation driven by polyunsaturated fatty acid (PUFA) oxidation compromises feed quality and animal health. Single antioxidants (e.g., ethoxyquin (EQ), butylated hydroxytoluene (BHT)) face limitations including dose-dependent toxicity, bioaccumulation risks, and inadequate protection against multistage oxidation. Composite systems leveraging complementary mechanisms offer a promising alternative. This study evaluated synergistic efficacy of rationally formulated composite antioxidants (combining synthetic radical scavengers and metal chelators) versus single-component systems in enhancing lipid oxidative stability in high-fat animal feed. The basal diet containing oxidized oil served as the control group (CON). Seven groups were supplemented with the basal diet as follows: Treatment A, 36 g/ton Butylated Hydroxytoluene (BHT); Treatment B, 60 g/ton Ethoxyquin (EQ); Treatment C, 132 g/ton EQ; Treatment D, 10 g/ton EQ + 12 g/ton BHT; Treatment E, 10 g/ton EQ + 12 g/ton BHT + 6 g/ton Citric acid (CA); Treatment F, 20 g/ton EQ + 6 g/ton BHT + 6 g/ton CA; and treatment G, 2 g/ton EQ + 25 g/ton BHT + 6 g/ton CA. Oxidative stability was assessed over a 10-week period under natural storage (T0-T10) and acute thermal stress (120 °C drying for 2 h followed by ambient storage; HT0 to HT10). Oxidative stability was assessed via: antioxidant capacity (DPPH (2,2-Diphenyl-1-picrylhydrazyl)/ABTS (2,2′-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging, total antioxidant capacity), physical indices: Color (L*, a*, b*), and chemical oxidation markers: conjugated dienes (CD), peroxide value (PV), p-anisidine value (p-AV), malondialdehyde (MDA), acid value (AV), total oxidation (TOTOX). Superior synergistic performance of the ternary blend (Treatment E) was demonstrated versus singles (A/B/C). Retention of radical scavenging capacity was significantly enhanced, with greater stability observed under accelerated storage. Primary oxidation (PV) and secondary oxidation (MDA, p-AV) were most effectively suppressed by Treatment E. Superior color stability (minimal L* change) was maintained under thermal stress. The lowest TOTOX values were achieved across all conditions by Treatment E. Stage-specific vulnerabilities were shown by single antioxidants (BHT volatilization; pro-oxidative effects of EQ at high doses). Comprehensive, temperature-resilient protection was delivered collectively by the synergistic EQ+BHT+CA system (Treatment E) via combined radical quenching and metal chelation. The inherent limitations of individual antioxidants were effectively overcome by the optimized composite, enabling reduced total dosage while substantially extending the lipid oxidative stability period. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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Graphical abstract

20 pages, 1221 KiB

Open AccessReview

Molecular Duality of OGG1: From Genomic Guardian to Redox-Sensitive Modulator in Diseases

by Ranwei Zhong, Weiran Zhang, Xiangping Qu, Yang Xiang and Ming Ji

Antioxidants 2025, 14(8), 980; https://doi.org/10.3390/antiox14080980 - 10 Aug 2025

Abstract

Inflammation, malignant tumors, and age-related disorders are all associated with oxidative DNA damage. 8-oxoguanine DNA glycosylase 1 (OGG1), which recognizes and repairs intracellular oxidative damage, was initially thought to play a pivotal role in cellular repair of such damage. However, a growing body [...] Read more.

Inflammation, malignant tumors, and age-related disorders are all associated with oxidative DNA damage. 8-oxoguanine DNA glycosylase 1 (OGG1), which recognizes and repairs intracellular oxidative damage, was initially thought to play a pivotal role in cellular repair of such damage. However, a growing body of evidence now indicates that OGG1 not only participates in DNA oxidative damage repair but also possesses transcription factor activity, closely linked to the development and progression of oxidative DNA damage-related diseases. We propose that OGG1 can repair damaged DNA, while in certain diseases, OGG1 promotes transcription and exacerbates disease progression. This review discusses the mechanisms of action of OGG1 and proposes it as an emerging therapeutic target for curing the aforementioned diseases. Full article

(This article belongs to the Special Issue Redox Biology and Genomic Integrity)

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28 pages, 1017 KiB

Open AccessReview

Naringin and Naringenin in Liver Health: A Review of Molecular and Epigenetic Mechanisms and Emerging Therapeutic Strategies

by Roberto Flores-Peña, Hugo Christian Monroy-Ramirez, Fernando Caloca-Camarena, Scarlet Arceo-Orozco, Jorge Alejandro Salto-Sevilla, Marina Galicia-Moreno and Juan Armendariz-Borunda

Antioxidants 2025, 14(8), 979; https://doi.org/10.3390/antiox14080979 - 10 Aug 2025

Abstract

Liver diseases have become a significant global health concern, driving increased interest in naturally occurring compounds as adjunctive treatments for managing these conditions. Flavonoids, a class of natural polyphenols found in plants and fruits, offer a broad spectrum of potential health benefits due [...] Read more.

Liver diseases have become a significant global health concern, driving increased interest in naturally occurring compounds as adjunctive treatments for managing these conditions. Flavonoids, a class of natural polyphenols found in plants and fruits, offer a broad spectrum of potential health benefits due to their applications in nutraceuticals, pharmaceuticals, and cosmetics. Among them, naringin (NARI) and naringenin (NAR), which are abundant in citrus fruits, have attracted considerable attention. Numerous studies have investigated the therapeutic effects of NARI and NAR across different stages of liver disease. This review highlights recent research on the impact of these flavonoids in alcohol-related liver disease and metabolic dysfunction-associated fatty liver disease (MASLD). It also explores the molecular mechanisms and epigenetic modifications through which NARI and NAR contribute to preventing liver disease progression. Finally, this work discusses recent progresses and future perspectives, emphasizing the role of innovative nanocarriers, nanoparticles, and drug delivery strategies in enhancing the efficacy and bioavailability of these promising compounds to improve liver health. Full article

(This article belongs to the Special Issue Dietary Antioxidant Compounds and Liver Health: Pharmacological Activities and Molecular Mechanisms)

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15 pages, 4595 KiB

Open AccessArticle

Oxidative Stress Triggers Porcine Ovarian Granulosa Cell Apoptosis Through MAPK Signaling

by Ting Zhao, Hui Jia, Xuerui Zhao, Xiaotong Gu, Chaoxiong Yong, Saihao Wang, Jiawei Zhou, Linrong Li, Mailin Gan, Lili Niu, Ye Zhao, Lei Chen, Xiaofeng Zhou, Linyuan Shen, Li Zhu and Yan Wang

Antioxidants 2025, 14(8), 978; https://doi.org/10.3390/antiox14080978 - 9 Aug 2025

Abstract

Follicle health determines the number and quality of sows’ ovulation, thereby influencing the litter size and the piglets’ viability. Granulosa cells (GCs) play a crucial role in follicular formation and development, and oxidative stress-induced GC death is a major cause of follicular dysplasia. [...] Read more.

Follicle health determines the number and quality of sows’ ovulation, thereby influencing the litter size and the piglets’ viability. Granulosa cells (GCs) play a crucial role in follicular formation and development, and oxidative stress-induced GC death is a major cause of follicular dysplasia. Previous studies have confirmed that oxidative stress triggers apoptosis in granulosa cells. In this study, we explored how oxidative stress influences apoptosis in porcine ovarian granulosa cells. We find that porcine atretic follicles exhibit significant oxidative stress, accompanied by the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, including the upregulation of key factors such as apoptosis signal-regulating kinase 1 (ASK1). Healthy follicles of 3–5 mm were randomly assigned to the control group, H₂O₂ treatment group, and selonsertib pretreatment group. The porcine ovarian GCs were placed in cell culture medium supplemented with H₂O₂ to assess ROS production, cell proliferation, apoptosis, the expression levels of oxidative stress-related genes, and expression levels of apoptosis-related proteins. In vitro experiments in mouse GCs further confirmed that H₂O₂-induced oxidative stress triggers the upregulation of the MAPK pathway and promotes granulosa cell apoptosis. The results showed that H₂O₂ treatment induced ROS production and apoptosis in porcine GCs and inhibited GC viability. Additionally, selonsertib pretreatment attenuated apoptosis in GCs by inhibiting H₂O₂-induced oxidative stress. In summary, our findings reveal that oxidative stress induced granulosa cell apoptosis via the MAPK signaling pathway, impairing proper follicular development in pigs. Full article

(This article belongs to the Special Issue Recent Advances in Applications of Antioxidants in Livestock Health and Reproduction)

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15 pages, 1252 KiB

Open AccessArticle

LC-MS Evaluation of the Redox Trypanothione Balance in Leishmania infantum Parasites

by Théo Villarubias, Jade Royo, Pierre Perio, Sandra Bourgeade-Delmas, Jan Sudor, Alexis Valentin, Anne-Dominique Terrisse and Karine Reybier

Antioxidants 2025, 14(8), 977; https://doi.org/10.3390/antiox14080977 - 8 Aug 2025

Abstract

Leishmaniases are neglected tropical diseases caused by protozoan parasites of the Leishmania genus, with a significant global health burden, particularly in low-income regions. The parasites rely on a unique thiol-based redox system centered on trypanothione, which is essential for survival under oxidative stress [...] Read more.

Leishmaniases are neglected tropical diseases caused by protozoan parasites of the Leishmania genus, with a significant global health burden, particularly in low-income regions. The parasites rely on a unique thiol-based redox system centered on trypanothione, which is essential for survival under oxidative stress encountered during their life cycle in both insect vectors and mammalian hosts. Given the absence of mammalian analogs, the trypanothione system represents an attractive target for antileishmanial drug development. However, accurate quantification of the reduced and oxidized forms of trypanothione has been challenging due to its instability and structural similarity between redox states. Here, we developed and validated a rapid, sensitive liquid chromatography–mass spectrometry (LC-MS) method for assessing the trypanothione redox state in Leishmania infantum. By incorporating N-ethylmaleimide as a thiol-blocking agent during sample preparation, the native redox state was preserved, enabling precise measurement of the reduced-to-oxidized ratio. Our approach demonstrated high sensitivity (nanomolar range), a rapid analysis time (5 min/sample), and robustness across various conditions. Moreover, we validated the method’s relevance in detecting oxidative stress and response to the trypanothione reductase inhibitor auranofin. This LC-MS technique provides a valuable tool for exploring Leishmania redox biology and supports the discovery of redox-targeting therapies against leishmaniasis. Full article

(This article belongs to the Section ROS, RNS and RSS)

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19 pages, 2688 KiB

Open AccessArticle

Optimizing Antioxidant and Biological Activities of Quercus Fructus: Synergistic Role of Inner Shell and Extraction Methods

by Jin Gyeom Kim, Hajeong Kim, Beulah Favour Ortutu, Woochan Jeong, Su-In Yoon, Inhwa Han and Jin Ah Cho

Antioxidants 2025, 14(8), 976; https://doi.org/10.3390/antiox14080976 - 8 Aug 2025

Abstract

This study comprehensively evaluated how the inclusion of the inner shell and the choice of extraction method influence the antioxidant activity of Quercus Fructus (QF). Eight QF extracts were prepared with or without the inner shell using stirring (S) and ultrasonication (U) with [...] Read more.

This study comprehensively evaluated how the inclusion of the inner shell and the choice of extraction method influence the antioxidant activity of Quercus Fructus (QF). Eight QF extracts were prepared with or without the inner shell using stirring (S) and ultrasonication (U) with 80% ethanol, boiled water (B) and autoclave (A) with distilled water. Among them, the ultrasonication extract with inner shell (IU) exhibited the highest antioxidant capacity, showing strong DPPH radical scavenging (228.8 mg TEAC/g), ABTS activity (162.9 mg TEAC/g), reducing power (380.9 mg TERP/g), and SOD-like activity (38.1%). HPLC-UV profiling identified quercetin-7-glucoside (Q7G) as a major detectable compound, although several polar phenolics remained unidentified. In LPS-stimulated Raw 264.7 cells, IU significantly suppressed nitric oxide production and iNOS expression without cytotoxicity. Additionally, IU treatment markedly reduced ROS accumulation in H₂O₂-exposed zebrafish embryos. These findings suggest that including the inner shell with ultrasonication extraction synergistically enhances QF’s antioxidant efficacy, suggesting a practical strategy for maximizing the functional potential of QF in natural antioxidant development. Full article

(This article belongs to the Special Issue Plant Antioxidants, Inflammation, and Chronic Disease)

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18 pages, 1166 KiB

Open AccessArticle

Association Between Oxidative–Inflammation Biomarkers and Incident Chronic Kidney Disease in People with High Cardiovascular Risk: A Nested Case–Control Study

by Maria Magdalena Quetglas-Llabrés, Andrés Díaz-López, Cristina Bouzas, Margalida Monserrat-Mesquida, Jordi Salas-Salvadó, Miguel Ruiz-Canela, J. Alfredo Martínez, José Manuel Santos-Lozano, Silvia García, Ramon Estruch, José López-Miranda, Dora Romaguera, Francisco J. Tinahones, Marcos García-Fernández, Sebastián Mas-Fontao, Pilar Matía-Martín, Jesús Vioque, Aurora Bueno, Nancy Babio, Josep A. Tur and Antoni Sureda Show full author list Hide full author list

Antioxidants 2025, 14(8), 975; https://doi.org/10.3390/antiox14080975 - 8 Aug 2025

Abstract

Aim: To assess oxidative–inflammatory biomarker prediction of incident CKD after 1-year follow-up in a population with overweight/obesity and metabolic syndrome. Methods: Prospective nested case–control study comprising 117 CKD incident cases and 117 matched controls free of CKD after 1-year follow-up conducted [...] Read more.

Aim: To assess oxidative–inflammatory biomarker prediction of incident CKD after 1-year follow-up in a population with overweight/obesity and metabolic syndrome. Methods: Prospective nested case–control study comprising 117 CKD incident cases and 117 matched controls free of CKD after 1-year follow-up conducted in 55–75-year-old participants. Controls were time-matched 1:1 to cases by intervention group, age (≤65 vs. >65 years), and sex. Serum creatinine (SCr), cystatin C (CyC), and urine albumin-to-creatinine ratio (UACR) were measured at baseline, and CKD Epidemiology Collaboration equations for Caucasians were used to assess SCr, CyC, and CyC-SCr-based estimated Glomerular Filtration Rate (eGFR). Baseline levels of malondialdehyde (MDA), carbonyls, tumour necrosis factor alpha (TNFα), interleukin (IL)-1β, IL-1ra, IL-6, monocyte chemoattractant protein 1 (MCP-1), and leptin were determined from fasting serum samples. An inflammatory-oxidative stress score based on these biomarkers was calculated. Incident CKD was defined by eGFR-SCr <60 mL/min/1.73 m², and/or UACR ≥30 mg/g in the absence of CKD at baseline. Results: UACR positively correlated with pro-inflammatory markers (IL-1β; TNFα) and oxidative damage marker (MDA); eGFR-cyC showed negative correlations with IL-1β and IL-1ra, and eGFR-SCr with leptin. The odds ratios (OR; 95% CI) for incident CKD in the highest vs. the lowest tertile of IL-1ra IL-6 and TNFα were (2.22; 1.22–4.04), (7.03; 2.88–17.14), and (3.79; 1.79–8.02), respectively. The inflammatory–oxidative stress score was associated with incident CKD (OR per 1-SD increment: 2.06; 1.49–2.83). Conclusions: Inflammatory/oxidative stress is associated with CKD incidence in individuals with high cardiovascular risk, underscoring the importance in identify early inflammation to prevent this disease. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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21 pages, 6405 KiB

Open AccessArticle

Methyl Jasmonate Orchestrates Multi-Pathway Antioxidant Defense to Enhance Salt Stress Tolerance in Walnut (Juglans regia L.)

by Ruining Nie, Chengxu Wu, Xinying Ji, Ao Li, Xu Zheng, Jiajia Tang, Leyuan Sun, Yi Su and Junpei Zhang

Antioxidants 2025, 14(8), 974; https://doi.org/10.3390/antiox14080974 - 8 Aug 2025

Abstract

Walnut (Juglans regia L.), an ecologically and economically important species, requires the elucidation of its salt stress response mechanisms for improved salt tolerance breeding. This study elucidates the physiological and molecular mechanisms through which exogenous methyl jasmonate (MeJA) mitigates salt stress in [...] Read more.

Walnut (Juglans regia L.), an ecologically and economically important species, requires the elucidation of its salt stress response mechanisms for improved salt tolerance breeding. This study elucidates the physiological and molecular mechanisms through which exogenous methyl jasmonate (MeJA) mitigates salt stress in walnut, providing novel strategies for salt-tolerant cultivar development. This integrated study combined physiological, biochemical, and multi-omics analyses to decipher how exogenous MeJA enhances ROS scavenging through the synergistic activation of phenylalanine (Phe), tryptophan (Trp), and α-linolenic acid pathways, establishing a multilevel antioxidant defense network. MeJA treatment effectively mitigated salt stress-induced oxidative damage, as demonstrated by a significant 16.83% reduction in malondialdehyde (MDA) content, concurrent 11.60%, 10.73% and 22.25% increases in superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, respectively, the elevation of osmoregulatory soluble sugars (SS), and 1.2- to 2.0-fold upregulation of key antioxidant enzyme genes (SOD, POD, APX, GPX, DHAR) and elevated osmoregulatory substances (soluble sugars, SS). Improved photosynthetic parameters (P_n, G_s) and chlorophyll fluorescence efficiency (F_v/F_m) collectively indicated reduced oxidative stress (improved by 7.97–23.71%). Joint metabolomic-transcriptomic analyses revealed MeJA-enhanced ROS scavenging via the coordinated regulation of Phe, Trp, and α-linolenic acid pathways. In summary, MeJA significantly enhanced reactive oxygen species (ROS) scavenging efficiency and comprehensive antioxidant capacity in walnut seedlings through the synergistic regulation of key metabolic pathways, effectively mitigating salt stress. These findings establish a crucial mechanistic foundation for understanding plant salt stress responses and advance the utilization of MeJA-mediated strategies for the genetic improvement of salinity tolerance in walnut. Future research should prioritize optimizing MeJA application protocols and functionally validating key regulatory genes for breeding applications. Full article

(This article belongs to the Special Issue Oxidative Stress in Plant Stress and Plant Physiology)

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16 pages, 1210 KiB

Open AccessArticle

Perilla Seed Meal Extract Enriched with Rosmarinic Acid and Luteolin: Natural Active Pharmaceutical Ingredients (NAPIs) for Osteoprotective Effects

by Thanawat Pattananandecha, Sutasinee Apichai, Treethip Sukkho, Jetsada Ruangsuriya, Fumihiko Ogata, Naohito Kawasaki and Chalermpong Saenjum

Antioxidants 2025, 14(8), 973; https://doi.org/10.3390/antiox14080973 - 8 Aug 2025

Abstract

Perilla seed meal (PSM) is a waste biomass of perilla seed extraction that retains flavonoid and phenolic compounds. In this study, we aimed to investigate the potential of PSM extracts (PSMEs) from Perilla frutescens (L.) Britton as a sustainable source of natural active [...] Read more.

Perilla seed meal (PSM) is a waste biomass of perilla seed extraction that retains flavonoid and phenolic compounds. In this study, we aimed to investigate the potential of PSM extracts (PSMEs) from Perilla frutescens (L.) Britton as a sustainable source of natural active pharmaceutical ingredients (NAPIs) containing rosmarinic acid and luteolin for promoting bone health. PSMEs were obtained through shaking incubation and ultrasonic extraction, with 40% ethanol (PS-E40) and 80% ethanol (PS-E80) being found to be the most effective solvents. The effects of PSMEs on bone formation markers were evaluated in human fetal osteoblast cells (hFOB 1.19) using bone formation parameters. The results demonstrated that PS-E40 and PS-E80 extracts significantly increased alkaline phosphatase (ALP) activity, osteocalcin (OC) production, and osteoprotegerin (OPG) levels while concurrently reducing receptor activator of nuclear factor kappa-Β ligand (RANKL) and reactive oxygen species (ROS) production in a dose-dependent manner, particularly at 100 µg/mL on day 7 and 50 and 100 µg/mL on day 14 of the co-incubation period. Moreover, Alizarin Red S staining demonstrated that PS-E40 enhanced calcium deposition in both normal and osteogenic media, further supporting the effect of PSMEs on mineralization and osteoblast differentiation. Our findings suggest that PSMEs rich in rosmarinic acid and luteolin enhance bone health by promoting osteoblast activity and reducing osteoclastogenesis. Full article

(This article belongs to the Special Issue Bioactive Antioxidants from Agri-Food Wastes)

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21 pages, 1056 KiB

Open AccessReview

Carnitine Shuttle and Ferroptosis in Cancer

by Ye-Ah Kim, Yoonsung Lee and Man S. Kim

Antioxidants 2025, 14(8), 972; https://doi.org/10.3390/antiox14080972 - 8 Aug 2025

Abstract

Ferroptosis is a unique type of regulated cell death characterized by iron-dependent lipid peroxidation, and it has emerged as a promising therapeutic target in cancer treatment. The carnitine shuttle system, which is crucial for transporting fatty acids across the mitochondrial membrane, has been [...] Read more.

Ferroptosis is a unique type of regulated cell death characterized by iron-dependent lipid peroxidation, and it has emerged as a promising therapeutic target in cancer treatment. The carnitine shuttle system, which is crucial for transporting fatty acids across the mitochondrial membrane, has been identified as a key regulator of ferroptosis in cancer cells. This review investigates the intricate relationship between the carnitine shuttle and ferroptosis in cancer. We provide a comprehensive review of how the components of the carnitine system, including carnitine palmitoyltransferase 1A (CPT1A), carnitine palmitoyltransferase 2, and carnitine-acylcarnitine translocase, influence cellular redox homeostasis, fatty acid metabolism, and interact with proteins related to ferroptosis sensitivity. We discuss therapeutic implications of targeting the carnitine shuttle system, particularly CPT1A, to overcome ferroptosis resistance and enhance the efficacy of immunotherapy in various cancer types. This review offers further research directions, highlighting the crosstalk between the carnitine shuttle, ferroptosis, and various signaling pathways involved in cancer progression to improve cancer treatment. Full article

(This article belongs to the Special Issue Implication of Oxidative Stress in Promoting Cellular Senescence and Associated Pathologies—2nd Edition)

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18 pages, 2350 KiB

Open AccessArticle

Normalization of Oxygen Levels Induces a Metabolic Reprogramming in Livers Exposed to Intermittent Hypoxia Mimicking Obstructive Sleep Apnea

by Miguel Á. Hernández-García, Beatriz Aldave-Orzáiz, Carlos Ernesto Fernández-García, Esther Fuertes-Yebra, Esther Rey, Ángela Berlana, Ramón Farré, Carmelo García-Monzón, Isaac Almendros, Pedro Landete and Águeda González-Rodríguez

Antioxidants 2025, 14(8), 971; https://doi.org/10.3390/antiox14080971 - 7 Aug 2025

Abstract

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization [...] Read more.

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

(This article belongs to the Special Issue Oxidative Stress in Sleep Disorders)

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