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Naringin vs. Citrus x paradisi L. Peel Extract: An In Vivo Journey into Oxidative Stress Modulation
The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases
Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage
Effect of n-3 Polyunsaturated Fatty Acids Enriched Chicken Meat Consumption in Relation to Oxidative Stress Marker Levels in Young Healthy Individuals: A Randomized Double-Blind Study
Inflammasomes in Alzheimer’s Progression: Nrf2 as a Preventive Target

Journal Description

Antioxidants

Antioxidants is an international, peer-reviewed, open access journal, published monthly online by MDPI. The International Coenzyme Q10 Association (ICQ10A), Israel Society for Oxygen and Free Radical Research (ISOFRR) and European Academy for Molecular Hydrogen Research (EAMHR) are affiliated with Antioxidants and their members receive discounts on the article processing charge.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, FSTA, PubAg, CAPlus / SciFinder, and other databases.
Journal Rank: JCR - Q1 (Chemistry, Medicinal) / CiteScore - Q1 (Food Science)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.9 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2024).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Testimonials: See what our editors and authors say about Antioxidants.
Companion journal: Oxygen.

Impact Factor: 6.0 (2023); 5-Year Impact Factor: 6.7 (2023)

Imprint Information Journal Flyer Open Access ISSN: 2076-3921

Latest Articles

27 pages, 1753 KiB

Open AccessReview

Vitamin C in Cardiovascular Disease: From Molecular Mechanisms to Clinical Evidence and Therapeutic Applications

by Yichen Xu, Huabo Zheng, Ioana Slabu, Elisa Anamaria Liehn and Mihaela Rusu

Antioxidants 2025, 14(5), 506; https://doi.org/10.3390/antiox14050506 - 23 Apr 2025

Vitamin C, also known as ascorbic acid, is an essential nutrient that humans cannot synthesize, making its intake crucial for health. Discovered nearly a century ago, vitamin C is widely recognized for its ability to prevent scurvy and has become one of the [...] Read more.

Vitamin C, also known as ascorbic acid, is an essential nutrient that humans cannot synthesize, making its intake crucial for health. Discovered nearly a century ago, vitamin C is widely recognized for its ability to prevent scurvy and has become one of the most commonly used supplements. Beyond its antioxidant activity, vitamin C is pivotal in regulating lipid metabolism, promoting angiogenesis, enhancing collagen synthesis, modulating remodeling, and stabilizing the extracellular matrix. While preclinical studies have shown promising results, clinical trials have yielded inconsistent findings, due to suboptimal study design, results misinterpretation, and misleading conclusions. This review provides a holistic overview of existing evidence on the pleiotropic role of vitamin C in cardiovascular diseases, identifying both the strengths and limitations of current research and highlighting gaps in understandings in vitamin C’s underlying mechanisms. By integrating molecular insights with clinical data and evaluating the pleiotropic role of vitamin C in cardiovascular disease management and prevention, this review aims to guide future research toward personalized, evidence-based therapeutic strategies in clinical practice. Full article

(This article belongs to the Special Issue Antioxidant Therapies in Cardiovascular, Cardiorenal and Metabolic Diseases)

17 pages, 729 KiB

Open AccessArticle

Composition and Antioxidant Status of Vegan Milk—Pilot Study

by Agnieszka Chrustek, Agnieszka Dombrowska-Pali and Dorota Olszewska-Słonina

Antioxidants 2025, 14(5), 505; https://doi.org/10.3390/antiox14050505 - 23 Apr 2025

Background: More and more women are following a vegan and vegetarian diet. For some, the use of a vegan diet during lactation is controversial. Purpose: The aim of the study was to comparatively analyze the concentration of selected hormones, micro- and macronutrients, vitamins, [...] Read more.

Background: More and more women are following a vegan and vegetarian diet. For some, the use of a vegan diet during lactation is controversial. Purpose: The aim of the study was to comparatively analyze the concentration of selected hormones, micro- and macronutrients, vitamins, and the basic composition and antioxidant status of the milk of vegan women, compared to the milk of omnivorous women. Methods: The study included 17 breastfeeding vegan women and 27 omnivorous women. The basic composition of human milk was analyzed using the MIRIS HMATM analyzer (Uppsala, Sweden) The levels of hormones and vitamins were determined by the enzyme-linked immunosorbent method. In order to determine the antioxidant activity and micro- and macroelements, spectrophotometric methods were used. Results: The vegan group was characterized by a lower average age, lower BMI, and lower WHR index compared to the control group. The milk of vegan women showed significantly higher cortisol concentrations and lower iron, vitamin B6, and antioxidant status than the milk of omnivorous women. Conclusions: A vegan diet helps maintain a healthy body weight and is more popular among younger women, under 30 years of age. Higher levels of milk cortisol in vegan women may indicate a high level of anxiety and stress experienced by breastfeeding women, which may have negative consequences not only for breastfeeding mothers but also for the development of their children. Lack of appropriate supplementation in women who do not consume meat and animal products may cause a deficiency of micro- and macroelements in breast milk. Full article

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

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19 pages, 5097 KiB

Open AccessArticle

Impact of Melatonin Application in Winemaking on Phenolic Content, Tryptophan Metabolites, and Bioactivity of Red Wine

by Neda Đorđević, Nevena Todorović Vukotić, Ivana Perić, Otilija Keta, Vladana Petković, Snežana B. Pajović and Branislav Nastasijević

Antioxidants 2025, 14(5), 504; https://doi.org/10.3390/antiox14050504 - 23 Apr 2025

Global wine consumption drives the interest for high-quality wine with enhanced health benefits. Yeast-produced tryptophan metabolites, including melatonin, a potent antioxidant, emerged as promising agents for enhancing functional properties of food and beverages. This study represents the pioneering work addressing whether melatonin supplementation [...] Read more.

Global wine consumption drives the interest for high-quality wine with enhanced health benefits. Yeast-produced tryptophan metabolites, including melatonin, a potent antioxidant, emerged as promising agents for enhancing functional properties of food and beverages. This study represents the pioneering work addressing whether melatonin supplementation during vinification affects Moldova red wine quality. Total phenolic/flavonoid contents, DPPH, and FRAP assays were measured via spectrophotometry, anthocyanins, and tryptophan metabolites using UPLC-MS/MS and UPLC-FLD, as well as cytotoxicity with the MTT assay. Results showed that addition of melatonin during the winemaking process increased total phenolic/flavonoid content, as well as the antioxidant capacity evidenced by increased anti-DPPH radical activity. These effects might be due to the stimulation of phenolic compound biosynthesis, particularly anthocyanins malvidin-3-O-glucoside, peonidin-3-O-glucoside, and delphinidin 3-O-glucoside, which were found to be increased in the treated wine. Additionally, the study revealed that melatonin-enriched wine exhibited increased cytotoxicity against two cancer cell lines, HCT116 and PANC-1. Finally, melatonin supplementation enhanced the concentration of kynurenic acid, which, due to its cytoprotective and antioxidant properties, could further increase the health benefits of the resulting wine. These findings offer promising avenue for future research of melatonin-driven functional properties of wine and provide step forward to a natural product with added value. Full article

(This article belongs to the Special Issue Free-Radical Scavenging and Antioxidant Properties of Melatonin, 2nd Edition)

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16 pages, 3661 KiB

Open AccessArticle

Mechanism of Astragalus Polysaccharide in Alleviating Bovine Mammary Fibrosis Through ROS/NLRP3 Inhibition and EMT Regulation

by Jiang Zhang, Kejiang Liu, Tingji Yang, Hongwei Duan, Longfei Xiao, Quanwei Zhang, Yong Zhang, Weitao Dong and Xingxu Zhao

Antioxidants 2025, 14(5), 503; https://doi.org/10.3390/antiox14050503 - 23 Apr 2025

Mastitis in dairy cows, typically caused by bacterial infection, is a common inflammatory condition of the mammary tissue that leads to fibrosis, adversely affecting cow health, milk production, and dairy product quality. Astragalus polysaccharide (APS) has shown effectiveness in alleviating inflammation and fibrosis [...] Read more.

Mastitis in dairy cows, typically caused by bacterial infection, is a common inflammatory condition of the mammary tissue that leads to fibrosis, adversely affecting cow health, milk production, and dairy product quality. Astragalus polysaccharide (APS) has shown effectiveness in alleviating inflammation and fibrosis in various organs. The study employed lipopolysaccharide (LPS) to induce fibrotic conditions in two experimental systems: MAC-T bovine mammary epithelial cells and Kunming mouse models. Key parameters, including relative gene mRNA expression, protein levels, and reactive oxygen species (ROS) levels, were assessed using RT-qPCR, Western blotting (WB), and 2’,7’-Dichlorofluorescin diacetate (DCFH-DA) techniques, while histological analysis of mammary tissue was performed using H&E and Masson trichrome staining. Measuring malondialdehyde (MDA) levels, assessing the enzyme activities of catalase (CAT), and superoxide dismutase (SOD) were two methods of assessing oxidative stress. These methods were also tested in mouse mammary glands. APS significantly decreased ROS concentrations (p < 0.01), restored oxidative stress balance in mice (p < 0.05), and reduced fibrosis and inflammation, as demonstrated by histological observations and analysis. It also exerted regulatory effects on fibrosis markers (E-cadherin, N-cadherin, α-SMA) and inflammation markers (NLRP3, ASC, Caspase-1, IL-1β), as demonstrated by changes in their mRNA and protein expression. These findings endorse APS’s viability as an alternative therapeutic agent for mammary fibrosis therapy by demonstrating its ability to inhibit epithelial-mesenchymal transition (EMT) in vitro and mammary fibrosis in vivo, while also mitigating ROS production and reducing inflammation. Full article

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16 pages, 1167 KiB

Open AccessArticle

Phenolic Acid Composition of Coffee Cascara in Connection with Antioxidant Capacity: A Geographic Assessment

by Ningjian Liang, David D. Kitts, Xiwen Wang, Ziying Hu and Maidinai Sabier

Antioxidants 2025, 14(5), 502; https://doi.org/10.3390/antiox14050502 (registering DOI) - 22 Apr 2025

Coffee cascara is an underutilized byproduct of coffee processing that has the potential for value-added applications due to its rich phytochemical content and antioxidant properties. The aim of this study was to characterize the phytochemical composition and antioxidant activity of coffee cascara sourced [...] Read more.

Coffee cascara is an underutilized byproduct of coffee processing that has the potential for value-added applications due to its rich phytochemical content and antioxidant properties. The aim of this study was to characterize the phytochemical composition and antioxidant activity of coffee cascara sourced from seven geographic regions, and where possible, a variety of farms in different regions. We compared two different extraction methods: hot water/sonication-assisted extraction and methanol–water extraction to generate phytochemical content. The antioxidant capacity of extracts was assessed through different assays. Correlations between phytochemical compounds and different antioxidant activities were analyzed first using Pearson’s correlations and then substantiated further using principal component analysis (PCA). The dominant phytochemicals identified in the extracted coffee cascara included gallic acid, chlorogenic acid isomers, mangiferin, protocatechuic acid and rutin. Among the water-extracted samples, the Brazil sample exhibited the highest oxygen radical absorbance capacity (ORAC) value, whereas the Zambia sample had the highest 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) value and the Laos sample showed the greatest inhibition of 2′,7′-Dichlorofluorescein diacetate (DCFH-DA) fluorescence. For methanol extracts, the highest ORAC and ABTS values were from the Indonesia sample, and the Laos sample showed the strongest inhibition of DCFH-DA fluorescence. The results show the distinct phytochemical composition and antioxidant activity of coffee cascara according to geographical clustering using PCA. Specifically, gallic acid, p-hydroxybenzoic acid and to a lesser extent rutin correlated (p < 0.05) with ABTS and DCFH-DA assays. This study revealed significant variation in the chemical composition and antioxidant properties of coffee cascara across different geographic regions; less so with different farms associated with the location. The findings offer evidence for potential upscaling of coffee cascara waste for use in value-added functional food or nutraceutical applications. Full article

(This article belongs to the Special Issue Antioxidant Activity of Polyphenolic Extracts)

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25 pages, 1135 KiB

Open AccessReview

Targeting Redox Signaling Through Exosomal MicroRNA: Insights into Tumor Microenvironment and Precision Oncology

by Moon Nyeo Park, Myoungchan Kim, Soojin Lee, Sojin Kang, Chi-Hoon Ahn, Trina Ekawati Tallei, Woojin Kim and Bonglee Kim

Antioxidants 2025, 14(5), 501; https://doi.org/10.3390/antiox14050501 - 22 Apr 2025

Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that [...] Read more.

Reactive oxygen species (ROS) play a dual role in cancer progression, acting as both signaling molecules and drivers of oxidative damage. Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that modulates immune responses, angiogenesis, and therapeutic resistance. In particular, oxidative stress not only stimulates exosome biogenesis but also influences the selective packaging of redox-sensitive miRNAs (miR-21, miR-155, and miR-210) via RNA-binding proteins such as hnRNPA2B1 and SYNCRIP. These miRNAs, delivered through exosomes, alter gene expression in recipient cells and promote tumor-supportive phenotypes such as M2 macrophage polarization, CD8⁺ T-cell suppression, and endothelial remodeling. This review systematically explores how this ROS–miRNA–exosome axis orchestrates communication across immune and stromal cell populations under hypoxic and inflammatory conditions. Particular emphasis is placed on the role of NADPH oxidases, hypoxia-inducible factors, and autophagy-related mechanisms in regulating exosomal output. In addition, we analyze the therapeutic relevance of natural products and herbal compounds—such as curcumin, resveratrol, and ginsenosides—which have demonstrated promising capabilities to modulate ROS levels, miRNA expression, and exosome dynamics. We further discuss the clinical potential of leveraging this axis for cancer therapy, including strategies involving mesenchymal stem cell-derived exosomes, ferroptosis regulation, and miRNA-based immune modulation. Incorporating insights from spatial transcriptomics and single-cell analysis, this review provides a mechanistic foundation for the development of exosome-centered, redox-modulating therapeutics. Ultimately, this work aims to guide future research and drug discovery efforts toward integrating herbal medicine and redox biology in the fight against cancer. Full article

(This article belongs to the Special Issue Role of Reactive Oxygen Species (ROS) in Tumor Microenvironment Modulation)

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19 pages, 6041 KiB

Open AccessArticle

Allantoin Serves as a Novel Risk Factor for the Progression of MASLD

by Weiqiang Lv, Xueqiang Wang, Zhaode Feng, Cunxiao Sun, Hansen Wu, Mengqi Zeng, Tianlin Gao, Ke Cao, Jie Xu, Xuan Zou, Tielin Yang, Hao Li, Lei Chen, Jiankang Liu, Shanshan Dong and Zhihui Feng

Antioxidants 2025, 14(5), 500; https://doi.org/10.3390/antiox14050500 - 22 Apr 2025

Uric acid (UA), traditionally recognized as an extracellular antioxidant, exhibits paradoxical associations with metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD), though its mechanistic contributions remain elusive. Here, we integrate multi-modal evidence to explore the role of UA and its oxidative [...] Read more.

Uric acid (UA), traditionally recognized as an extracellular antioxidant, exhibits paradoxical associations with metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD), though its mechanistic contributions remain elusive. Here, we integrate multi-modal evidence to explore the role of UA and its oxidative metabolite, allantoin, in MASLD progression. Analysis of UK Biobank data revealed a strong association between elevated UA levels and increased risks of MASLD and type 2 diabetes (T2D). However, Mendelian randomization analysis of over 2 million samples demonstrated causal effects of urate solely on serum triglycerides and T2D risk. Targeted metabolomics in an elderly Chinese cohort identified allantoin, an oxidative by-product of UA, significantly elevated in individuals with dyslipidemia or T2D, with serum allantoin levels positively correlated with fasting glucose, triglycerides, and cholesterol. Animal studies indicated that allantoin exacerbates hepatic lipid accumulation and glucose intolerance in high-fat diet mice, driven by increased hepatic lipid biogenesis and reduced bile acid production. Notably, further research revealed a strong binding affinity of allantoin for PPARα, leading to the suppression of PPARα activity, which promotes the progression of MASLD. These findings underscore the critical role of allantoin, rather than UA, as a critical driver of MASLD development, offering valuable insights for the prediction and management of hepatic metabolic disorders. Full article

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

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27 pages, 12816 KiB

Open AccessArticle

Differential Cell Death Pathways Induced by Oxidative Stress in Multi-Organs of Amur Grayling (Thymallus grubii) Under Gradient Ammonia Stress

by Cunhua Zhai, Yutao Li, Ruoyu Wang, Ying Zhang and Bo Ma

Antioxidants 2025, 14(4), 499; https://doi.org/10.3390/antiox14040499 - 21 Apr 2025

Ammonia nitrogen is a common contaminant in aquatic environments, and its potential toxicity to organisms has attracted extensive attention. However, few studies have comprehensively evaluated the negative impacts of ammonia stress on cold-water fish. In this study, liver, gill, and intestine specimens of [...] Read more.

Ammonia nitrogen is a common contaminant in aquatic environments, and its potential toxicity to organisms has attracted extensive attention. However, few studies have comprehensively evaluated the negative impacts of ammonia stress on cold-water fish. In this study, liver, gill, and intestine specimens of Amur grayling (Thymallus grubii) from three treatment groups (control (0 mg/L), low ammonia (43.683 mg/L), and high ammonia (436.8 mg/L)), were collected for histological observation, biochemical examination, and transcriptomic, metabolomic, and intestinal microbiome analysis. Our results showed that excessive ammonia nitrogen blocked the normal immune function and compromised the integrity of liver and gill tissues through oxidative stress-mediated differential cell death pathways. Meanwhile, the multi-omics analysis revealed that ammonia exposure predominantly altered the carbohydrate, lipid, and amino acid metabolism modes. In addition, it was also demonstrated that ammonia nitrogen stress affected the composition of intestinal microbiota taxa. This study provides insights into the potential risks and hazards of ammonia stress on cold fish in natural waters and provides a reference for the environment control of the water quality in aquaculture. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)

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35 pages, 1430 KiB

Open AccessReview

Synthetic and Natural Agents Targeting Advanced Glycation End-Products for Skin Anti-Aging: A Comprehensive Review of Experimental and Clinical Studies

by Joon Yong Choi, Nam Gyoung Ha, Weon Ju Lee and Yong Chool Boo

Antioxidants 2025, 14(4), 498; https://doi.org/10.3390/antiox14040498 - 20 Apr 2025

Advanced glycation end-products (AGEs) cause blood vessel damage and induce diabetic complications in various organs, such as the eyes, kidneys, nerves, and skin. As glycation stress causes aesthetic, physical, and functional changes in the skin, glycation-targeting skin anti-aging strategies are attracting attention in [...] Read more.

Advanced glycation end-products (AGEs) cause blood vessel damage and induce diabetic complications in various organs, such as the eyes, kidneys, nerves, and skin. As glycation stress causes aesthetic, physical, and functional changes in the skin, glycation-targeting skin anti-aging strategies are attracting attention in cosmetology and dermatology. The primary goal of this review is to understand the significance of glycation-induced skin aging and to examine the therapeutic potential of glycation-targeting strategies. This study covers experimental and clinical studies exploring various interventions to attenuate glycation-induced skin aging. Glycation stress decreases the viability of cells in culture media, the cell-mediated contraction of collagen lattices in reconstructed skin models, and the expression of fibrillin-1 at the dermo-epidermal junction in the skin explants. It also increases cross-links in tail tendon collagen in animals, prolonging its breakdown time. However, these changes are attenuated by several synthetic and natural agents. Animal and clinical studies have shown that dietary or topical administration of agents with antiglycation or antioxidant activity can attenuate changes in AGE levels (measured by skin autofluorescence) and skin aging parameters (e.g., skin color, wrinkles, elasticity, hydration, dermal density) induced by chronological aging, diabetes, high-carbohydrate diets, ultraviolet radiation, or oxidative stress. Therefore, the accumulating experimental and clinical evidence supports that dietary supplements or topical formulations containing one or more synthetic and natural antiglycation agents may help mitigate skin aging induced by AGEs. Full article

(This article belongs to the Special Issue Antioxidants for Skin Health)

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13 pages, 2887 KiB

Open AccessArticle

Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of Antioxidants

by Jin-Yi Han, Hideo Utsumi and Han-Young Chung

Antioxidants 2025, 14(4), 497; https://doi.org/10.3390/antiox14040497 - 20 Apr 2025

Collagen plays a crucial role in platelet activation and thrombosis, yet the underlying mechanisms involving reactive oxygen species (ROS) remain incompletely understood. This study investigated how collagen modulates ROS generation and platelet aggregation both in vitro and in vivo, as well as evaluating [...] Read more.

Collagen plays a crucial role in platelet activation and thrombosis, yet the underlying mechanisms involving reactive oxygen species (ROS) remain incompletely understood. This study investigated how collagen modulates ROS generation and platelet aggregation both in vitro and in vivo, as well as evaluating the protective effects of antioxidants. In vitro, collagen induced dose-dependent platelet aggregation and increased ROS generation, evidenced by the enhanced EMPO adduct formation detected via electron spin resonance (ESR). In vivo experiments demonstrated that collagen administration significantly accelerated CAT-1 decay, indicating elevated oxidative stress with a transient peak around 1 minute post-treatment. Furthermore, escalating collagen doses correlated with increased ROS generation and reduced survival rates in mice, underscoring collagen’s impact on oxidative stress and thrombosis severity. Importantly, treatment with enzymatic antioxidants (superoxide dismutase, catalase) and non-enzymatic antioxidants (DMTU, Tiron, mannitol) significantly attenuated collagen-induced oxidative stress and improved animal survival. Collectively, these findings elucidate the pivotal role of ROS in collagen-induced platelet activation and thrombosis and highlight antioxidants as promising therapeutic candidates for preventing thrombotic disorders and managing cardiovascular risk. Full article

(This article belongs to the Special Issue Blood Cells and Redox Homeostasis in Health and Disease, 2nd Edition)

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22 pages, 7200 KiB

Open AccessArticle

Genome-Wide Identification of the Sulfate Transporter Gene Family Reveals That BolSULTR2;1 Regulates Plant Resistance to Alternaria brassicicola Through the Modulation of Glutathione Biosynthesis in Broccoli

by Guize Wu, Yunhua Ding, Ning Li, Hongji Zhang and Ning Liu

Antioxidants 2025, 14(4), 496; https://doi.org/10.3390/antiox14040496 - 20 Apr 2025

Sulfate transporters (SULTRs) are key players that regulate sulfur acquisition and distribution within plants, thereby influencing cellular redox hemostasis under pathogen attacks, such as Alternaria brassicicola (Ab). In this study, a total of 23 BolSULTR (Brassica oleracea SULTR) genes were [...] Read more.

Sulfate transporters (SULTRs) are key players that regulate sulfur acquisition and distribution within plants, thereby influencing cellular redox hemostasis under pathogen attacks, such as Alternaria brassicicola (Ab). In this study, a total of 23 BolSULTR (Brassica oleracea SULTR) genes were identified from the Brassica genome. These BolSULTRs are distributed across nine chromosomes, with all collinear BolSULTR gene pairs undergoing purifying selections. Phylogenetic analysis reveals that the SULTR family is evolutionarily conserved among plant kingdoms. qRT-PCR analysis demonstrated that the expression of BolSULTRs varies across different plant organs and is modulated by hormonal signals. Furthermore, transcriptome analysis identified several BolSULTRs whose expression levels were depressed in Ab-challenged leaves in broccoli. Among them, the BolSULTR2;1 gene emerged as a key player in the plant’s response to Ab. Virus-induced gene silencing (VIGS) of BolSULTR2;1s resulted in elevated glutathione (GSH) levels and enhanced tolerance to Ab. Taken together, these findings underscore the role of BolSULTR2;1 in maintaining redox homeostasis and enhancing plant disease resistance, suggesting its potential as a target for genome editing to develop broccoli varieties with improved pathogen tolerance. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants, 2nd Edition)

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24 pages, 22656 KiB

Open AccessArticle

Influence of High Temperature and Ammonia and Nitrite Accumulation on the Physiological, Structural, and Genetic Aspects of the Biology of Largemouth Bass (Micropterus salmoides)

by Yuexing Zhang, Hui Qiao, Leyang Peng, Yujie Meng, Guili Song, Cheng Luo and Yong Long

Antioxidants 2025, 14(4), 495; https://doi.org/10.3390/antiox14040495 - 20 Apr 2025

Hyperthermia and nitrogenous pollutants like ammonia and nitrite are common risk factors that adversely affect fish health and pose significant threats to the aquaculture industry. However, the impacts of high temperatures on the accumulation of nitrogenous pollutants in the water of the aquaculture [...] Read more.

Hyperthermia and nitrogenous pollutants like ammonia and nitrite are common risk factors that adversely affect fish health and pose significant threats to the aquaculture industry. However, the impacts of high temperatures on the accumulation of nitrogenous pollutants in the water of the aquaculture systems and their toxicity to farmed fish are not well understood. In this study, juvenile largemouth bass (Micropterus salmoides, LMB) were kept at 28 °C and 34 °C in a closed aquatic system to investigate the effects of higher temperatures on ammonia and nitrite accumulation. The fish were fed 2% of their body weight daily for a 14-day experiment. Ammonia levels gradually increased, peaking on day 7 at 34 °C and on day 9 at 28 °C, then decreased to near zero. Nitrite levels remained low initially and increased rapidly along with the reduction in ammonia levels at both temperatures. The 34 °C high temperature accelerated the accumulation of ammonia and its transformation into nitrite compared to 28 °C. Fish were sampled on day 1 (low ammonia and low nitrite, LALN), day 8 (high ammonia and low nitrite, HALN), and day 14 (low ammonia and high nitrite, LAHN) to explore toxic effects. Successive exposure to high levels of ammonia and nitrite caused oxidative stress in the liver and significant pathogenic changes in the liver and spleen, with more pronounced impacts observed at 34 °C. Significant changes in gene expression were detected in the liver and spleen of fish sampled at HALN and LAHN, compared to those at LALN, with upregulated genes primarily associated with extracellular matrix (ECM) and cytoskeleton organization. A second experiment was conducted at the same temperatures but without ammonia/nitrite accumulation. The results of this experiment confirmed the combined effects of hyperthermia and ammonia/nitrite toxicity on the expression of genes involved in ECM–receptor interaction and TGF-beta signaling. These findings are valuable for optimizing cultivation environments and promoting the health of farmed LMB. Full article

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18 pages, 6741 KiB

Open AccessArticle

Competitive Ligand-Induced Recruitment of Coactivators to Specific PPARα/δ/γ Ligand-Binding Domains Revealed by Dual-Emission FRET and X-Ray Diffraction of Cocrystals

by Shotaro Kamata, Akihiro Honda, Sayaka Yashiro, Chihiro Kaneko, Yuna Komori, Ayumi Shimamura, Risa Masuda, Takuji Oyama and Isao Ishii

Antioxidants 2025, 14(4), 494; https://doi.org/10.3390/antiox14040494 - 20 Apr 2025

Peroxisome proliferator-activated receptors (PPARs), composed of the α/δ/γ subtypes, are ligand-activated nuclear receptors/transcription factors that sense endogenous fatty acids or therapeutic drugs to regulate lipid/glucose metabolism and oxidative stress. PPAR forms a multiprotein complex with a retinoid X receptor and corepressor complex in [...] Read more.

Peroxisome proliferator-activated receptors (PPARs), composed of the α/δ/γ subtypes, are ligand-activated nuclear receptors/transcription factors that sense endogenous fatty acids or therapeutic drugs to regulate lipid/glucose metabolism and oxidative stress. PPAR forms a multiprotein complex with a retinoid X receptor and corepressor complex in an unliganded/inactive state, and ligand binding induces the replacement of the corepressor complex with the coactivator complex to initiate the transcription of various genes, including the metabolic and antioxidant ones. We investigated the processes by which the corepressor is replaced with the coactivator or in which two coactivators compete for the PPARα/δ/γ-ligand-binding domains (LBDs) using single- and dual-emission fluorescence resonance energy transfer (FRET) assays. Single-FRET revealed that the respective PPARα/δ/γ-selective agonists (pemafibrate, seladelpar, and pioglitazone) induced the dissociation of the two corepressor peptides, NCoR1 and NCoR2, from the PPARα/δ/γ-LBDs and the recruitment of the two coactivator peptides, CBP and TRAP220. Meanwhile, dual-FRET demonstrated that these processes are simultaneous and that the four coactivator peptides, CBP, TRAP220, PGC1α, and SRC1, were competitively recruited to the PPARα/δ/γ-LBDs with different preferences upon ligand activation. Furthermore, the five newly obtained cocrystal structures using X-ray diffraction, PPARα-LBDs–NCoR2/CBP/TRAP220/PGC1α and PPARγ-LBD–NCoR2, were co-analyzed with those from our previous studies. This illustrates that these coactivators bound to the same PPARα-LBD loci via their consensus LXXLL motifs in the liganded state; that NCoR1/NCoR2 corepressors bound to the same loci via the IXXXL sequences within their consensus LXXXIXXXL motifs in the unliganded state; and that ligand activation induced AF-2 helix 12 formation that interfered with corepressor binding and created a binding space for the coactivator. These PPARα/γ-related biochemical and physicochemical findings highlight the coregulator dynamics on limited PPARα/δ/γ-LBDs loci. Full article

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23 pages, 4552 KiB

Open AccessArticle

Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and Cardiotoxicity

by Bamaprasad Dutta, Shining Loo, Antony Kam, Xiaoliang Wang, Na Wei, Kathy Qian Luo, Chuan-Fa Liu and James P. Tam

Antioxidants 2025, 14(4), 493; https://doi.org/10.3390/antiox14040493 - 19 Apr 2025

(1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side-effects from oxidative stress, leading to cardiotoxicity, pose significant challenges to its clinical use. We recently discovered a novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins from Panax ginseng that we term ginsentides. [...] Read more.

(1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side-effects from oxidative stress, leading to cardiotoxicity, pose significant challenges to its clinical use. We recently discovered a novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins from Panax ginseng that we term ginsentides. Ginsentides, such as the 31-residue TP1, coordinate multiple biological systems to prevent vascular dysfunction and endoplasmic reticulum stress induced by internal and external stressors. (2) Methods: We assessed the protective effects of ginsentide TP1 on DOX-induced cardiotoxicity using both in vitro functional studies on H9c2 cardiomyocytes and in vivo animal models by zebrafish and ICR mouse models. In these models, we examined oxidative stress, apoptosis, intracellular calcium levels, mitochondrial function, inflammatory responses, and cardiac function. (3) Results: We show that ginsentide TP1 protects against DOX-induced cytotoxicity in the mitochondria-rich H9c2 cardiomyocytes and reduces myocardial injury in zebrafish and mice by mitigating oxidative stress, inflammation, calcium, and mitochondrial dysfunction, as well as apoptosis-mediated cell death. Importantly, TP1 preserves cellular homeostasis without compromising the anticancer potency of DOX in breast cancer cells. (4) Conclusions: our findings highlight a specific antioxidative function of ginsentide TP1 in managing DOX-induced cardiotoxicity during cancer treatment and provide a promising lead for developing cardioprotective peptides and microproteins against oxidative stress. Full article

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

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44 pages, 6718 KiB

Open AccessReview

Advanced Glycation End Products in Disease Development and Potential Interventions

by Yihan Zhang, Zhen Zhang, Chuyue Tu, Xu Chen and Ruikun He

Antioxidants 2025, 14(4), 492; https://doi.org/10.3390/antiox14040492 - 18 Apr 2025

Advanced glycation end products (AGEs) are a group of compounds formed through non-enzymatic reactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs can be generated in the body or introduced through dietary sources and smoking. Recent clinical and animal studies have [...] Read more.

Advanced glycation end products (AGEs) are a group of compounds formed through non-enzymatic reactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs can be generated in the body or introduced through dietary sources and smoking. Recent clinical and animal studies have highlighted the significant role of AGEs in various health conditions. These compounds accumulate in nearly all mammalian tissues and are associated with a range of diseases, including diabetes and its complications, cardiovascular disease, and neurodegeneration. This review summarizes the major diseases linked to AGE accumulation, presenting both clinical and experimental evidence. The pathologies induced by AGEs share common mechanisms across different organs, primarily involving oxidative stress, chronic inflammation, and direct protein cross-linking. Interventions targeting AGE-related diseases focus on inhibiting AGE formation using synthetic or natural antioxidants, as well as reducing dietary AGE intake through lifestyle modifications. AGEs are recognized as significant risk factors that impact health and accelerate aging, particularly in individuals with hyperglycemia. Monitoring AGE level and implementing nutritional interventions can help maintain overall health and reduce the risk of AGE-related complications. Full article

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

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20 pages, 17279 KiB

Open AccessArticle

In Vitro Structural Characteristics and Antioxidant and Expectorant Activities of Polysaccharides from Citri grandis fructus immaturus

by Jingwen Li, Suifen Mo, Yingshan Feng, Yan Xiang, Chen Ni, Qing Luo, Jing Zhou, Yujia Wang, Ruoting Zhan and Ping Yan

Antioxidants 2025, 14(4), 491; https://doi.org/10.3390/antiox14040491 - 18 Apr 2025

The aim of this study was to investigate the structural characteristics of four polysaccharides derived from Citri grandis fructus immaturus and their antioxidant and expectorant activities. ECP1 fraction passing through a 500 kDa dialysis bag (ECP1A) and ECP2 fraction retained in a 300 [...] Read more.

The aim of this study was to investigate the structural characteristics of four polysaccharides derived from Citri grandis fructus immaturus and their antioxidant and expectorant activities. ECP1 fraction passing through a 500 kDa dialysis bag (ECP1A) and ECP2 fraction retained in a 300 kDa dialysis bag (ECP2B) had molecular weights of 340 and 1217 kDa, respectively. All four polysaccharides were composed of six monosaccharides, including l-rhamnose, d-arabinose, d-xylose, d-mannose, d-glucose, and d-galactose, with molar ratios of 1.99:52.38:6.99:2.64:5.15:31.15 for ECP1A and 1.54:65.13:6.34:2.51:3.58:22.07 for ECP2B. ECP1A had an α/β-glucopyranose ring, and the glycosyl groups were linked mainly by 1→4, 1→2, or 1→6 glycosidic bonds. It likely adopted a single-stranded helical conformation. ECP2B had a β-glucopyranose ring, and the glycosyl groups were linked mainly by 1→4, 1→2, or 1→6 glycosidic bonds. Furthermore, in vitro experiments showed that ECP1A displayed excellent antioxidant activity (IC₅₀ = 0.4614 mg/mL). ECP2B significantly inhibited MUC5AC mucin content expression in the mucus hypersecretion model of BEAS-2B cells, thus exerting an expectorant effect. A significant negative correlation was observed between the molecular weight of Citri grandis fructus immaturus polysaccharides and their antioxidant activity, and the uronic acid and d-arabinose contents of these polysaccharides exhibited strong negative trends with both antioxidant and expectorant activities. This study shows the potential for developing and utilizing polysaccharides from Citri grandis fructus immaturus as an antioxidant and expectorant agent. Full article

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23 pages, 10645 KiB

Open AccessArticle

Cyanidin-3-O-Glucoside Mitigates Amyloid-Beta (1–42)-Induced Apoptosis in SH-SY5Y Cells by Regulating Ca²⁺ Homeostasis and Inhibiting Mitochondrial Dysfunction

by Chao Ma, Yu Nie, Donglei Zhang, Lulu Ran, Su Xu, Xun Ran, Junya Huang and Lingshuai Meng

Antioxidants 2025, 14(4), 490; https://doi.org/10.3390/antiox14040490 - 18 Apr 2025

Background: Blueberry anthocyanin such as Cyanidin-3-O-glucoside may help prevent Alzheimer’s disease. We aimed to investigate the preventive and therapeutic effects of Cyanidin-3-O-glucoside against Aβ_1–42-induced apoptosis of SH-SY5Y cells as well as the underlying mechanisms. Methods: Cell viability [...] Read more.

Background: Blueberry anthocyanin such as Cyanidin-3-O-glucoside may help prevent Alzheimer’s disease. We aimed to investigate the preventive and therapeutic effects of Cyanidin-3-O-glucoside against Aβ_1–42-induced apoptosis of SH-SY5Y cells as well as the underlying mechanisms. Methods: Cell viability and intracellular and mitochondrial reactive oxygen species were detected by MTT, a reactive oxygen species detection kit, and a MitoSOX red mitochondrial superoxide indicator. The mitochondrial membrane potential, intracellular calcium ion content, and adenotriphophate (ATP) were identified via a mitochondrial membrane potential detection kit, calcium ion detection kit, and ATP detection kit, and apoptosis was detected via flow cytometry. Transcription of apoptosis-related genes was detected using real-time fluorescence quantitative polymerase chain reaction, and expression of apoptosis-related proteins was identified using Western blot. Results: We found that Cyanidin-3-O-glucoside could downregulate the expression of cytochrome c, caspase 9, caspase 3, and other genes and proteins, which consequently reduced the rate of apoptosis. Additionally, it could upregulate Bcl-2 gene and protein expression, downregulate Bax gene and protein expression, regulate mitochondrial membrane permeability and calcium-release channels, reduce calcium influx into mitochondria, maintain intracellular calcium ion levels, reduce intracellular levels of reactive oxygen species and increase ATP levels, maintain the mitochondrial membrane potential at a normal level, maintain normal mitochondrial functioning, and prevent apoptosis. Discussion: Taken together, Cyanidin-3-O-glucoside showed dose-dependent preventive and therapeutic effects against Aβ_1–42-induced apoptosis of SH-SY5Y cells. Conclusions: Cyanidin 3-O-glucoside showed a better preventive effect than therapeutic effect against Aβ_1–42-induced apoptosis in SH-SY5Y cells. Full article

(This article belongs to the Special Issue Antioxidant Activities of Phytochemicals in Fruits and Vegetables)

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23 pages, 995 KiB

Open AccessReview

Exploring Oxidative Stress Mechanisms of Nanoparticles Using Zebrafish (Danio rerio): Toxicological and Pharmaceutical Insights

by Denisa Batir-Marin, Monica Boev, Oana Cioanca, Ionut-Iulian Lungu, George-Alexandru Marin, Ana Flavia Burlec, Andreea-Maria Mitran, Cornelia Mircea and Monica Hancianu

Antioxidants 2025, 14(4), 489; https://doi.org/10.3390/antiox14040489 - 18 Apr 2025

Nanoparticles (NPs) have revolutionized biomedical and pharmaceutical applications due to their unique physicochemical properties. However, their widespread use has raised concerns regarding their potential toxicity, particularly mediated by oxidative stress mechanisms. This redox imbalance, primarily driven by the overproduction of reactive oxygen species [...] Read more.

Nanoparticles (NPs) have revolutionized biomedical and pharmaceutical applications due to their unique physicochemical properties. However, their widespread use has raised concerns regarding their potential toxicity, particularly mediated by oxidative stress mechanisms. This redox imbalance, primarily driven by the overproduction of reactive oxygen species (ROS), plays a central role in NP-induced toxicity, leading to cellular dysfunction, inflammation, apoptosis, and genotoxicity. Zebrafish (Danio rerio) have emerged as a powerful in vivo model for nanotoxicology, offering advantages such as genetic similarity to humans, rapid development, and optical transparency, allowing real-time monitoring of oxidative damage. This review synthesizes current findings on NP-induced oxidative stress in zebrafish, highlighting key toxicity mechanisms and case studies involving metallic (gold, silver, copper), metal oxide (zinc oxide, titanium dioxide, iron oxide), polymeric, and lipid-based NPs. The influence of NP physicochemical properties, such as size, surface charge, and functionalization, on oxidative stress responses is explored. Additionally, experimental approaches used to assess ROS generation, antioxidant enzyme activity, and oxidative damage biomarkers in zebrafish models are examined. In addition to toxicity concerns, pharmaceutical applications of antioxidant-modified NPs are evaluated, particularly their potential in drug delivery, neuroprotection, and disease therapeutics. Notably, studies show that curcumin- and quercetin-loaded nanoparticles enhance antioxidant defense and reduce neurotoxicity in zebrafish models, demonstrating their promise in neuroprotective therapies. Furthermore, cerium oxide nanoparticles, which mimic catalase and SOD enzymatic activity, have shown significant efficacy in reducing ROS and protecting against oxidative damage. Challenges in zebrafish-based nanotoxicology, the need for standardized methodologies, and future directions for optimizing NP design to minimize oxidative stress-related risks are also discussed. By integrating insights from toxicity mechanisms, case studies, and pharmaceutical strategies, this review supports the development of safer and more effective nanoparticle-based therapies while addressing the challenges of oxidative stress-related toxicity. Full article

(This article belongs to the Special Issue Natural Antioxidants in Pharmaceuticals and Dermatocosmetology)

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13 pages, 426 KiB

Open AccessArticle

The Effect of Antioxidant Administration on Semen Quality in Men with Infertility: A Randomized Placebo-Controlled Clinical Trial

by Pinelopi Ioannidou, Theodosia Zeginiadou, Christos Venetis, Dimitrios Papanikolaou, Leonidas Zepiridis, Despoina Savvaidou, Katerina Chatzimeletiou, Alexandros Lambropoulos, Dimitrios G. Goulis, Grigoris Grimbizis and Efstratios M. Kolibianakis

Antioxidants 2025, 14(4), 488; https://doi.org/10.3390/antiox14040488 - 18 Apr 2025

A randomized, placebo-controlled, quadruple-blind trial was performed to evaluate the effect of oral administration of the antioxidant combination Spermotrend^® for three months on semen quality in infertile men with at least one abnormal variable in semen analysis. Eighty men were randomized between [...] Read more.

A randomized, placebo-controlled, quadruple-blind trial was performed to evaluate the effect of oral administration of the antioxidant combination Spermotrend^® for three months on semen quality in infertile men with at least one abnormal variable in semen analysis. Eighty men were randomized between 2019 and 2022, receiving either the antioxidant combination Spermotrend^® (n = 40, spermotrend-group) or placebo (n = 40, placebo-group). Although a total of 80 patients were enrolled in the study, the final data is only from 70 patients. The primary outcome measure was sperm motility (rapid progressive, progressive, and total motility). The values of primary and secondary outcomes between treatment initiation and treatment completion were compared within groups. Moreover, their changes between treatment initiation and treatment completion were compared between the placebo- and the spermotrend-groups. Sperm rapid progressive motility significantly increased in infertile men treated for three months with antioxidant combination Spermotrend^® (+1.0%, 95% CI: 0.0 to +2.0, p = 0.04), while this increase was not observed in the placebo-group. Sperm progressive motility significantly increased in infertile men treated for three months with antioxidant combination Spermotrend^® (+3.0%, 95% CI: 0.0 to +15.1, p = 0.02), while this increase was not observed in the placebo-group. Similarly, DFI was significantly decreased in infertile men treated for three months by antioxidant combination Spermotrend^® (−3.2%, 95% CI: −5.8 to −0.5, p = 0.02). However, no statistically significant differences were observed in the changes of pre- and post-treatment values between the spermotrend- and the placebo-group regarding sperm progressive motility, concentration, normal morphology, DFI, and formation of 8-OH-dG. The antioxidant combination Spermotrend^® appears to exert limited benefit on sperm motility and DFI in infertile men with at least one abnormal variable in semen analysis. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Male Infertility)

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17 pages, 4696 KiB

Open AccessArticle

Potentillae argenteae herba—Antioxidant and DNA-Protective Activities, and Microscopic Characters

by Tsvetelina Andonova, Yordan Muhovski, Samir Naimov, Elena Apostolova, Silviya Mladenova, Ivayla Dincheva, Vasil Georgiev, Atanas Pavlov, Rumen Mladenov and Ivanka Dimitrova-Dyulgerova

Antioxidants 2025, 14(4), 487; https://doi.org/10.3390/antiox14040487 - 18 Apr 2025

Antioxidants from natural sources are essential for the development of new therapeutics to improve human health. The objects of study are the aerial flowering parts of Potentilla argentea, a plant species known in traditional medicine for the astringent, hemostatic, wound-healing, and anti-inflammatory [...] Read more.

Antioxidants from natural sources are essential for the development of new therapeutics to improve human health. The objects of study are the aerial flowering parts of Potentilla argentea, a plant species known in traditional medicine for the astringent, hemostatic, wound-healing, and anti-inflammatory effects of its rhizomes. A Potentillae argenteae herba ethanol dry tincture was chromatographically analyzed (GC/MS, HPLC) and its antioxidant (ABTS, DPPH, CUPRAC, FRAP assays) and DNA nicking protection potentials were evaluated. The eighteen volatiles were identified by GC/MS, where the predominant components were n-nonacosane (39.38 mg/g dt), squalene (28.88 mg/g dt), n-tricosane (18.36 mg/g dt), ethyl oleate (15.24 mg/g dt), and n-pentacosane (10.60 mg/g dt). A high content of total polyphenols was obtained (440.78 mg GAE/g dt), and HPLC analysis identified two flavonoids and three phenolic acids, of which rosmarinic acid and rutin were above 10 mg/g dt. The tincture exhibited strong antioxidant activity by all four methods, especially CUPRAC assay (8617.54 μM TE/g). DNA protective activity against oxidative damage and microscopic identification of P. argenteae herba powder were established for the first time. Therefore, the tincture could be incorporated into phytopreparations for the treatment of human diseases caused by reactive oxygen species. Full article

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

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