Antioxidants

16 pages, 5501 KB

Open AccessReview

Beyond Food Preservation: Translational Perspectives of Synthetic Antioxidants

by Daniela Vergara, Felipe Lizama, Carlos Arias-Fuentes, Emigdio Chávez-Ángel and Alejandro Castro-Alvarez

Antioxidants 2026, 15(8), 973; https://doi.org/10.3390/antiox15080973 - 5 Aug 2026

Abstract

Synthetic antioxidants are attracting more interest as research moves beyond their traditional use as preservatives in food and materials. Recent studies are exploring how these redox-active molecules might be used in medicine. This review looks at how synthetic antioxidants are made, what is [...] Read more.

Synthetic antioxidants are attracting more interest as research moves beyond their traditional use as preservatives in food and materials. Recent studies are exploring how these redox-active molecules might be used in medicine. This review looks at how synthetic antioxidants are made, what is known about their biological effects, and the challenges of using them for neuroprotection, cancer treatment, organ protection, and regenerative medicine. In this review, synthetic antioxidants are defined as synthetic or semisynthetic small molecules with redox activity. Other antioxidant systems, such as non-phenolic molecules, prodrugs, peptides, metal complexes, nanocarriers, nanozymes, and biomaterials, are mentioned as related but are not considered classic synthetic antioxidants. Some of these compounds and delivery systems have shown promising results in cell, tissue, and animal studies. They have been found to influence neuroinflammation, mitochondrial function, and tumor redox responses, and to protect tissues from ischemic or inflammatory damage. However, most of these candidates are still in preclinical development. Progress is slowed by issues such as inconsistent bioavailability, dose-dependent toxicity, unclear mechanisms of action, a lack of reliable biomarkers, and manufacturing or regulatory challenges, especially for advanced delivery systems. New research highlights the potential of hybrid molecules, organelle-targeted delivery, and systems that respond to specific triggers. Still, there is not enough strong clinical data to support these approaches. Moving forward, the field will need thorough pharmacological studies, careful safety checks, standardized ways to measure effectiveness, and well-designed clinical trials. Full article

(This article belongs to the Special Issue Recent Trends in Nanoantioxidants—2nd Edition)

► Show Figures

Figure 1

25 pages, 9935 KB

Open AccessReview

Oxidative Stress as a Potential Mechanistic Bridge Between Electronic Cigarette Components and Chronic Disease: A Combined Narrative and Bibliometric Analysis

by Rana Abdel Sater, Youssef El Rayess and Sofi G. Julien

Antioxidants 2026, 15(8), 972; https://doi.org/10.3390/antiox15080972 - 5 Aug 2026

Abstract

Despite their introduction two decades ago as cessation tools, vaping devices and electronic cigarettes (ECs) have surged dramatically among adolescents and adults worldwide. The widespread misconception that ECs are harmless has raised substantial concern about their potential contribution to chronic diseases associated with [...] Read more.

Despite their introduction two decades ago as cessation tools, vaping devices and electronic cigarettes (ECs) have surged dramatically among adolescents and adults worldwide. The widespread misconception that ECs are harmless has raised substantial concern about their potential contribution to chronic diseases associated with oxidative stress (OS) pathways. To map this rapidly growing field, we combined a bibliometric analysis of human research on vaping-associated OS over the past decade with a narrative review of EC component toxicology and regulatory updates. The bibliometric analysis of 189 human studies identified four keyword clusters reflecting clinico-epidemiological, biological/mechanistic, methodological, and acute-event research themes. The results of this bibliometric analysis structure the narrative synthesis, which evaluates the chemical constituents of ECs, including e-liquid constituents, device-derived contaminants, and their aerosol by-products, and links them to pathways associated with OS development. Oxidative stress was the most frequent bridging keyword, reflecting predominant academic trends as research shifted from acute-focused investigations toward mechanistic chronic disease research. No prior review has integrated EC component toxicology with bibliometric evidence to map this landscape. This combined approach provides researchers, clinicians, and policymakers with an integrated evidence base and identifies priority areas for future investigation, including long-term exposure thresholds, age- and sex-specific outcomes, and the urgent need for harmonized global regulation. Full article

(This article belongs to the Special Issue Cigarette Smoke and Oxidative Stress)

► Show Figures

Figure 1

20 pages, 3192 KB

Open AccessArticle

Jostaberry (Ribes × nidigrolaria) as a Functional Ingredient for 3D Printed Snacks: Impact of Starch Type and Storage on Antioxidant Profile and Stability

by Ana Mandura Jarić, Anica Bebek Markovinović, Luna Maslov Bandić, Josipa Ljubičić, Ana Valentić, Manuela Zadravec, Ana Vulić, Boris Duralija, Sandra Zavadlav and Danijela Bursać Kovačević

Antioxidants 2026, 15(8), 971; https://doi.org/10.3390/antiox15080971 - 5 Aug 2026

Abstract

The growing demand for functional foods and personalized nutrition has increased interest in three-dimensional printing (3DP) as a technology for developing customized food products. Jostaberry (Ribes × nidigrolaria), a fruit rich in antioxidant compounds, has rarely been explored in 3DP food [...] Read more.

The growing demand for functional foods and personalized nutrition has increased interest in three-dimensional printing (3DP) as a technology for developing customized food products. Jostaberry (Ribes × nidigrolaria), a fruit rich in antioxidant compounds, has rarely been explored in 3DP food applications. This study evaluated the suitability of jostaberry for producing 3DP snacks and investigated the effects of starch type (corn or wheat) and storage (12 days/4 °C) on physicochemical properties, bioactive compounds, antioxidant capacity, and microbiological stability. Both starch type and storage significantly influenced product characteristics, whereas storage was the main factor affecting stability. During storage, moisture loss, changes in total soluble solids, color differences, and reductions in organic acid concentrations were observed. Although condensed tannins and anthocyanins decreased by 27.6% and 37.3%, respectively, total phenolic content remained relatively stable, suggesting compound-specific changes rather than an overall loss of phenolics. Compared with wheat starch, corn starch resulted in higher total flavonoid and hydroxycinnamic acid contents, whereas wheat starch retained higher malic acid concentrations. Antioxidant capacity also gradually decreased during storage. Despite these changes, the 3DP snacks remained microbiologically stable and complied with food safety requirements throughout the storage period. These findings demonstrate that jostaberry is a promising functional ingredient for 3DP snacks, providing high bioactive potential and acceptable refrigerated storage stability. Full article

► Show Figures

Figure 1

19 pages, 12737 KB

Open AccessArticle

Cinnamomum migao Active Extracts Ameliorate Acute Myocardial Ischemia via Modulation of the HIF-1α/Nrf2/NF-κB/MAPK Pathway Downstream of Oxidative Stress

by Xiaofen Li, Yinju Zhang, Wenxia Dai, Ming Xia and Lang Zhou

Antioxidants 2026, 15(8), 970; https://doi.org/10.3390/antiox15080970 - 5 Aug 2026

Abstract

Acute myocardial ischemia (AMI) is a life-threatening cardiovascular disorder characterized by excessive oxidative stress and persistent inflammatory cascades, yet safe multi-target natural therapeutic agents remain scarce. Cinnamomum migao is a well-known Miao ethnic medicine used for cardiovascular conditions, yet its cardioprotective effects and [...] Read more.

Acute myocardial ischemia (AMI) is a life-threatening cardiovascular disorder characterized by excessive oxidative stress and persistent inflammatory cascades, yet safe multi-target natural therapeutic agents remain scarce. Cinnamomum migao is a well-known Miao ethnic medicine used for cardiovascular conditions, yet its cardioprotective effects and mechanisms remain largely unclear. This study investigated the efficacy and underlying mechanism of C. migao ethyl acetate extract (MGE) against AMI. MGE significantly improved the viability of H9c2 cardiomyocytes subjected to OGD/R injured. UPLC-MS/MS and molecular networking identified 30 constituents in MGE, among which sesquiterpenoids predominated. In ISO-induced AMI rats, MGE dose-dependently mitigated myocardial injury, as reflected by reduced ST-segment elevation, serum CK-MB and LDH levels, and alleviated histopathological damage. MGE enhanced SOD and CAT activities, decreased MDA content, and inhibited the secretion of TNF-α, IL-6 and IL-1β. Mechanistically, MGE downregulated the expression of NOX4, HIF-1α, p38 MAPK and NF-κB p65, while activating the Nrf2/HO-1 pathway. Oxyphyllenone A and magnodelavin C were identified as key active sesquiterpenoids that stably bound to IL-17 and TNF. Collectively, MGE alleviates AMI injury via anti-oxidative, anti-hypoxic, and anti-inflammatory effects through modulation of the HIF-1α/Nrf2/NF-κB/MAPK axis downstream of oxidative stress, with sesquiterpenoids serving as its key bioactive components. This work provides robust experimental evidence supporting C. migao as a promising natural antioxidant candidate for the prevention and treatment of AMI. Full article

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

► Show Figures

Figure 1

22 pages, 4040 KB

Open AccessArticle

Physiological Adaptation Strategy of the Pseudo-Metallophyte Lotus corniculatus L. to Long-Term Metal Contamination

by Marzena Sujkowska-Rybkowska, Anna Rusaczonek, Małgorzata Nykiel, Ewelina Hallmann, Maria Duszyn, Sławomir Jaworski and Wojciech Borucki

Antioxidants 2026, 15(8), 969; https://doi.org/10.3390/antiox15080969 - 5 Aug 2026

Abstract

Lotus corniculatus L. can spontaneously colonize metal-contaminated areas like the old Zn-Pb calamine tailings. This study compared two L. corniculatus ecotypes collected from metal-contaminated (HM) and non-contaminated (NM) sites to identify physiological adaptations to long-term metal exposure. The results indicated that HM ecotype [...] Read more.

Lotus corniculatus L. can spontaneously colonize metal-contaminated areas like the old Zn-Pb calamine tailings. This study compared two L. corniculatus ecotypes collected from metal-contaminated (HM) and non-contaminated (NM) sites to identify physiological adaptations to long-term metal exposure. The results indicated that HM ecotype accumulates Zn, Pb, and Cd in shoots without showing any toxic symptoms at the ultrastructural level. The HM ecotype exhibited a different composition of photosynthetic pigments, lower lipid peroxidation, and oxidative stress levels and increased the efficiency of the antioxidant defense system and antioxidant activity compared to the NM ecotype. Leaf antioxidant enzymes such as SOD, CAT, POX, and GPX were more active in the shoots of the HM ecotype, while GR and APX showed lower activity compared to the NM ecotype. In addition, the HM ecotype was characterized by higher glutathione and total phenolics content (mainly catechin, rutin, ferulic, and salicylic acids); however, these non-enzymatic metabolites primarily function in metal chelation alongside their role in oxidative stress mitigation. The results showed that calamine Lotus plants exhibit effective adaptation to long-term metal exposure by keeping metals away from metabolically active compartments and strengthening antioxidant defenses. These coordinated mechanisms reduce oxidative stress and contribute to the enhanced metal tolerance of calamine plants. Full article

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

► Show Figures

Figure 1

31 pages, 12497 KB

Open AccessArticle

Dietary Application of Synergistically Degraded Low-Molecular-Weight Chitosan to Promote Health and Antioxidant Responses in Pacific White Shrimp (Litopenaeus vannamei)

by Thitirat Rattanawongwiboon, Natthapong Paankhao, Wararut Buncharoen, Benchawan Kumwan, Pakapon Meachasompop, Yosapon Adisornprasert, Chonlatat Rajitdumrong, Pimrawee Chaemlek, Prapansak Srisapoome, Kasinee Hemvichian, Passakorn Kingwascharapong and Anurak Uchuwittayakul

Antioxidants 2026, 15(8), 968; https://doi.org/10.3390/antiox15080968 - 4 Aug 2026

Abstract

This study evaluated the potential of synergistically degraded low-molecular-weight chitosan (LMW-CS) as a functional feed additive to promote growth, antioxidant capacity, innate immunity, and disease resistance in Pacific white shrimp (Litopenaeus vannamei). High-molecular-weight chitosan (HMW-CS, approximately 85 kDa) was degraded using [...] Read more.

This study evaluated the potential of synergistically degraded low-molecular-weight chitosan (LMW-CS) as a functional feed additive to promote growth, antioxidant capacity, innate immunity, and disease resistance in Pacific white shrimp (Litopenaeus vannamei). High-molecular-weight chitosan (HMW-CS, approximately 85 kDa) was degraded using γ-irradiation in combination with H₂O₂ to produce LMW-CS with improved functional properties. Shrimp were fed five experimental diets for 4 weeks: a control diet, HMW-CS0.4 (0.4% w/w), LMW-CS0.1 (0.1% w/w), LMW-CS0.2 (0.2% w/w), and LMW-CS0.4 (0.4% w/w). Growth performance, oxidative stress markers, antioxidant enzyme activities, lysozyme activity, immune-related gene expression, bacterial load, and survival after Vibrio parahaemolyticus challenge were evaluated. The results indicate that dietary LMW-CS supplementation improved growth performance and feed utilization, with LMW-CS0.2 showing significantly higher final weight, total weight gain, and average daily gain than the control group (p < 0.05). Antioxidant assays showed that LMW-CS reduced malondialdehyde levels and increased reduced glutathione, nitric oxide, glutathione reductase, catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase activities in both plasma and hepatopancreas (p < 0.05). Lysozyme activity was significantly enhanced, particularly in the LMW-CS0.4 and HMW-CS0.4 groups (p < 0.05). Gene expression analysis revealed upregulation of genes associated with growth regulation, antimicrobial defense, pathogen recognition, and prophenoloxidase activation, including igf2, cstn, lgbp, lyz, and propo2. Gut microbiota profiling showed that chitosan supplementation altered bacterial community composition, reduced the relative abundance of some Vibrio-associated taxa, and descriptively lowered predicted pathogenic and stress-tolerant bacterial phenotypes. Following the Vibrio parahaemolyticus challenge, shrimp fed LMW-CS0.4 showed the lowest bacterial load and highest survival rate, indicating improved disease resistance (p < 0.05). Overall, synergistically degraded LMW-CS enhanced growth, redox balance, innate immune competence, gut microbial structure, and resistance to V. parahaemolyticus, supporting its potential as an antibiotic-free functional feed additive for sustainable shrimp aquaculture. Full article

(This article belongs to the Special Issue Antioxidants and Aquaculture: A Synergistic Approach for Sustainable Aquatic Production—2nd Edition)

► Show Figures

Figure 1

19 pages, 12372 KB

Open AccessArticle

Discovery and Preclinical Characterization of NE-2-6 as a Potent Thyroid Peroxidase Inhibitor with Antithyroid Activity

by Min-Gyu Lee, Suzie Kang, Hyun-Jun Kang and Cheol-Won Yun

Antioxidants 2026, 15(8), 967; https://doi.org/10.3390/antiox15080967 - 4 Aug 2026

Abstract

Graves’ disease is an autoimmune hyperthyroid disorder in which thyroid peroxidase (TPO) plays a central role in excessive thyroid hormone production. However, current TPO-targeting drugs, such as propylthiouracil, have limited selectivity and can cause serious adverse effects. In this study, we established an [...] Read more.

Graves’ disease is an autoimmune hyperthyroid disorder in which thyroid peroxidase (TPO) plays a central role in excessive thyroid hormone production. However, current TPO-targeting drugs, such as propylthiouracil, have limited selectivity and can cause serious adverse effects. In this study, we established an integrated discovery pipeline to identify and optimize novel small-molecule TPO inhibitors. The pipeline began with high-throughput screening of approximately 7000 compounds from the KRICT chemical library for peroxidase inhibition, followed by cytotoxicity filtering and iterative medicinal chemistry to generate NE-2 derivatives. Lead compounds (NE-2-6, NE-2-7, and NE-2-8) were evaluated using enzymatic assays, selectivity profiling against myeloperoxidase (MPO) and lactoperoxidase (LPO), molecular docking, plasma pharmacokinetic profiling, and in vivo antithyroid pharmacodynamic testing in an Ad-TSHR289-induced thyroid hyperfunction model. NE-2-6 exhibited potent TPO inhibitory activity and relative selectivity within the tested peroxidase panel. UV–visible spectral scanning and H₂O₂-dependent inhibition assays suggested that NE-2-6 perturbs the heme-associated catalytic environment of TPO; however, these data do not establish a definitive binding mode or kinetic inhibition mechanism. In the Ad-TSHR289-induced thyroid hyperfunction model, NE-2-6 reduced serum T4 levels, supporting antithyroid pharmacodynamic activity. Because autoimmune endpoints and dose-matched PK–PD relationships were not fully assessed, the findings should be interpreted as preliminary preclinical evidence supporting further evaluation of NE-2-6 as a TPO-targeting antithyroid candidate. Full article

(This article belongs to the Special Issue Advances in Peroxiredoxin Biology)

► Show Figures

Figure 1

14 pages, 930 KB

Open AccessArticle

Keratinocytes with DNA Aberration Induced by UVB Become Susceptible to Ferroptosis

by Yuliya D. Smirnova, Philipp Sabler, Adelheid Weidinger, Johannes Grillari, Peter Dungel and Andrey V. Kozlov

Antioxidants 2026, 15(8), 966; https://doi.org/10.3390/antiox15080966 - 3 Aug 2026

Abstract

Keratinocytes are key epidermal cells that are highly susceptible to ultraviolet (UV)-induced damage, which can lead to DNA mutations and the development of malignancies. In parallel, UV radiation induces lipid peroxidation (LPO), potentially facilitating the activation of ferroptosis, a form of programmed cell [...] Read more.

Keratinocytes are key epidermal cells that are highly susceptible to ultraviolet (UV)-induced damage, which can lead to DNA mutations and the development of malignancies. In parallel, UV radiation induces lipid peroxidation (LPO), potentially facilitating the activation of ferroptosis, a form of programmed cell death. We hypothesized that UV-mediated DNA damage, resulting in the formation of cyclobutane pyrimidine dimers (CPDs), occurs preferentially in cells with elevated LPO levels, and that mild induction of ferroptosis in proliferating keratinocytes selectively eliminates cells with high CPD levels. A human keratinocyte cell line was exposed to UVB radiation and subsequently treated with the ferroptosis inducers RSL3 and erastin. Cell death was assessed using LDH analysis, LPO was measured using the fluorescent probe BODIPY™ 581/591 C11, and CPD formation was quantified by ELISA. Using different doses of UVB, we confirmed UVB irradiation simultaneously increases the cell death rate and LPO and CPDs levels in proliferating keratinocytes. Mild induction of ferroptosis in these cells led to a slight increase in the cell death rate and simultaneously to a drastic reduction in CPD levels, suggesting that there is a specific pool of cells predominantly susceptible to UVB in terms of DNA damage and LPO induction. Our findings support our hypothesis that induction of ferroptosis in proliferating keratinocytes exposed to UVB radiation preferentially eliminates cells with elevated CPD levels and may therefore serve as a protective mechanism against UV-induced carcinogenesis. Full article

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

► Show Figures

Figure 1

28 pages, 6733 KB

Open AccessReview

The Dark Side of Antioxidants: When Scavenging ROS Undermines Plant Stress Acclimation

by Panqi Qiu, Ziwei Chu and Yurong Xie

Antioxidants 2026, 15(8), 965; https://doi.org/10.3390/antiox15080965 - 2 Aug 2026

Abstract

Reactive oxygen species (ROS) exert dual biological functions in plants. Though they form toxic byproducts of aerobic metabolism, ROS also serve as indispensable secondary messengers that orchestrate stress acclimation programs. For decades, plant physiologists operated under a pervasive assumption that constitutive and non-compartmentalized [...] Read more.

Reactive oxygen species (ROS) exert dual biological functions in plants. Though they form toxic byproducts of aerobic metabolism, ROS also serve as indispensable secondary messengers that orchestrate stress acclimation programs. For decades, plant physiologists operated under a pervasive assumption that constitutive and non-compartmentalized upregulation of antioxidant capacity would universally enhance abiotic stress tolerance. This long-standing dogma has now been thoroughly overturned. A growing body of evidence shows that sustained, global high antioxidant activity often impairs adaptation rather than helping it. In this review, we replace the simplistic “more antioxidants equal better tolerance” framework with a dynamic model of cellular redox homeostasis. We dissect three interconnected mechanisms though which unrestrained ROS scavenging generates deleterious phenotypic outcomes. First, indiscriminate clearance blunts transient ROS pulses and propagating ROS waves, the core signaling events acquired to trigger systemic acquired acclimation (SAA). Second, continuous antioxidant biosynthesis drains finite carbon skeletons, NADPH, and ATP pools, exacerbating evolutionary growth-defense resource trade-offs. Third, non-specific bulk ROS scavenging erases compartment-specific organellar retrograde signals, which rely on tightly controlled spatial and temporal ROS fluctuations. We concurrently define physiological boundary conditions where robust antioxidant activity remains vital for plant survival under extreme stress. Rather than advocating for the complete suppression of ROS detoxification, our analysis advocates context-dependent fine-tuning of redox signaling networks. We also summarize emerging precision redox monitoring and genetic engineering tools, and outline translational breeding pipelines to develop climate-resilient crops that balance stress survival and yield stability. This work delivers novel conceptual perspectives to advance fundamental plant redox biology. Full article

(This article belongs to the Special Issue Advances in Plant Redox Biology Research)

► Show Figures

Figure 1

20 pages, 6271 KB

Open AccessReview

Structure-Guided Design of Planarized Catechin Derivatives: Enhancing Antioxidant and Multifaceted Biological Activities for Therapeutic Applications

by Kiyoshi Fukuhara, Ikuo Nakanishi, Hiromu Ito, Wakana Shimizu, Yoshimi Shoji, Kei Ohkubo, Masao Morita, Sakurako Okada and Akiko Ohno

Antioxidants 2026, 15(8), 964; https://doi.org/10.3390/antiox15080964 - 1 Aug 2026

Abstract

Oxidative stress is a major driver of chronic disease, making natural polyphenols attractive scaffolds for modulating inflammation, proteostasis, and cell fate. However, green-tea catechins possess a twisted, conformationally flexible flavan-3-ol framework that limits π-conjugation, phenoxyl-radical stabilization, and productive interactions with biological targets. This [...] Read more.

Oxidative stress is a major driver of chronic disease, making natural polyphenols attractive scaffolds for modulating inflammation, proteostasis, and cell fate. However, green-tea catechins possess a twisted, conformationally flexible flavan-3-ol framework that limits π-conjugation, phenoxyl-radical stabilization, and productive interactions with biological targets. This review presents a structure-based framework in which conformational planarization serves as a strategy for functional amplification. Preorganization of the A/C–B inter-ring bond into a nearly coplanar arrangement reduces the conformational entropy penalty (−TΔS) upon binding or reaction while extending conjugation, strengthening π–π interactions, and facilitating redox reactions. This review highlights planarized catechin (PCat) architectures, including PCat–DTPA (a lesion-activated metal-responsive antioxidant), PCat–TrOH (a self-regenerating antioxidant network), procyanidin B3–PCat hybrids, and a planar silybin analog, illustrating how planarization and multivalent recognition enhance ROS regulation, inhibit amyloid-β aggregation and neurotoxicity, and suppress cancer cell phenotypes. Collectively, these studies establish PCat as a modular platform for the mechanism-informed design of disease-tailored phenolic antioxidants. Full article

(This article belongs to the Special Issue Phenolics as Antioxidant Agents—2nd Edition)

► Show Figures

Figure 1

16 pages, 3153 KB

Open AccessArticle

Protein Disulfide Isomerase A6 (PDIA6) Restrains Heat-Induced Oxidative Damage in Haemocytes of the Pacific Oyster (Crassostrea gigas)

by Pengcheng Sun, Ming Li, Peng Li, Yang Ma, Lei Gao, Xueshu Zhang, Lingling Wang and Linsheng Song

Antioxidants 2026, 15(8), 963; https://doi.org/10.3390/antiox15080963 - 1 Aug 2026

Abstract

Heat stress causes severe oxidative damage and immune cell death in marine bivalves, but its upstream regulators remain unclear. This study identified regulators linking heat stress to oxidative damage in Pacific oyster haemocytes. Under 30 °C exposure, the apoptosis rate of oyster haemocytes [...] Read more.

Heat stress causes severe oxidative damage and immune cell death in marine bivalves, but its upstream regulators remain unclear. This study identified regulators linking heat stress to oxidative damage in Pacific oyster haemocytes. Under 30 °C exposure, the apoptosis rate of oyster haemocytes increased from ~4.54% to 17.40% at 24 h, accompanied by elevated ROS, malondialdehyde, and lipid hydroperoxide and reduced SOD activity. GSEA and protein interaction analysis of the haemocyte transcriptome pinpointed protein disulfide isomerase A6 (CgPDIA6) as the hub gene linking endoplasmic reticulum stress, apoptosis, and oxidative stress. Single-cell in silico knockout placed CgPDIA6 at the head of a coupled SOD–peroxiredoxin relay (CgSOD1, CgSOD2, CgPRDX6) and shifted haemocytes toward a stress-activated state. This prediction was confirmed by RNAi knockdown, in which silencing CgPDIA6 aggravated heat-induced oxidative injury, reduced the expression of antioxidant-related genes (CgSOD1, CgSOD2, and CgPRDX6), and further suppressed SOD activity. Molecular dynamics simulations showed that heat destabilized its catalytic thioredoxin domains, compromising its protective function. These results demonstrate that CgPDIA6 protects haemocytes against heat-induced oxidative damage by sustaining antioxidant enzyme activity, providing insights into redox regulation and heat adaptation in mollusks. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defenses in Aquatic Animals)

► Show Figures

Figure 1

26 pages, 7256 KB

Open AccessArticle

Starvation Exacerbates Cold-Induced Synergistic Hepatic Injury in Pelteobagrus vachelli via Gut–Liver Axis Disruption and Ferroptosis-Related Metabolic Reprogramming

by Amei Liu, Libo Yang, Yuting Hu, Huaxing Zhou, Huan Wang and Guoqing Duan

Antioxidants 2026, 15(8), 962; https://doi.org/10.3390/antiox15080962 - 31 Jul 2026

Abstract

Overwintering represents a critical bottleneck for farmed fish, during which low temperature and starvation stress frequently co-occur, yet their synergistic effects on fish health remain poorly understood. Here, we exposed Pelteobagrus vachelli, a cold-sensitive freshwater species, to four conditions for 10 days: [...] Read more.

Overwintering represents a critical bottleneck for farmed fish, during which low temperature and starvation stress frequently co-occur, yet their synergistic effects on fish health remain poorly understood. Here, we exposed Pelteobagrus vachelli, a cold-sensitive freshwater species, to four conditions for 10 days: control (25 °C, feeding), starvation alone (25 °C, starvation), cold alone (11 °C, feeding), and combined cold–starvation (11 °C, starvation). Hepatic histopathology, antioxidant and liver function indices, gut microbiota (16S rRNA sequencing), and untargeted metabolomics (LC–MS) were integrated to elucidate gut–liver axis mechanisms underlying synergistic injury. Combined stress synergistically aggravated liver injury, as evidenced by hepatocellular vacuolation and necrosis, elevated aspartate aminotransferase (AST), alanine transaminase (ALT), malondialdehyde (MDA), and suppressed total superoxide dismutase (T–SOD), glutathione (GSH), catalase (CAT), and total antioxidant capacity (T–AOC). Two-way ANOVA confirmed significant interactive effects between cold and starvation stress (p < 0.05). Multi-omics revealed that dual stress uniquely activated multiple cell death pathways (FoxO, autophagy, ferroptosis, apoptosis), with marked oxidative phosphorylation (OXPHOS) activation and glutathione depletion—a signature absent under single stressors. Gut microbiota restructuring showed beneficial commensals (Cetobacterium, Prevotella, Lactobacillus) depleted and opportunistic pathogens (Plesiomonas, Pseudomonas, Flavobacterium) enriched, with Plesiomonas identified as the dominant biomarker (LDA score = 5.32). Integrative networks identified these pathogenic genera as hubs linking metabolic dysregulation to liver damage. Collectively, combined cold–starvation induces synergistic liver injury via gut–liver axis disruption, driving metabolic reprogramming and oxidative damage. These findings provide candidate biomarkers for overwintering stress monitoring and inform management strategies to mitigate cold–starvation-induced hepatic injury in aquaculture. Full article

► Show Figures

Figure 1

28 pages, 7016 KB

Open AccessSystematic Review

Brown Macroalgal Polyphenols and Oxidative Stress: A Systematic Review and Meta-Analysis of In Vivo Evidence in Vertebrate Models

by Dolores Cejalvo-Lapeña, Desiré Sánchez-Bonet, Samanta García-Oms, Mariola Belda-Antolí, José Miguel Lloris-Cejalvo and Carolina Padrón-Sanz

Antioxidants 2026, 15(8), 961; https://doi.org/10.3390/antiox15080961 - 31 Jul 2026

Abstract

Brown macroalgal polyphenols, particularly phlorotannins, have demonstrated antioxidant and anti-inflammatory bioactivity, but in vivo evidence remains heterogeneous across organisms, stress models, and preparations. This systematic review and meta-analysis synthesized in vivo evidence on the effects of brown macroalgal polyphenols on oxidative stress-related biomarkers. [...] Read more.

Brown macroalgal polyphenols, particularly phlorotannins, have demonstrated antioxidant and anti-inflammatory bioactivity, but in vivo evidence remains heterogeneous across organisms, stress models, and preparations. This systematic review and meta-analysis synthesized in vivo evidence on the effects of brown macroalgal polyphenols on oxidative stress-related biomarkers. PubMed, Cochrane, Scopus, and Web of Science were searched. Of 415 records identified, 22 in vivo studies involving zebrafish embryos, mice, and rats met the inclusion criteria. Interventions included extracts, fractions, and purified compounds. Random-effects meta-analyses were performed for prespecified outcomes, with subgroup analyses by compound, macroalgal species, and stressor/model. In zebrafish, brown macroalgal polyphenols reduced ROS generation, lipid peroxidation, and nitric oxide production. In rodents, they increased catalase activity and serum superoxide dismutase, and reduced hepatic malondialdehyde and TBARS, whereas glutathione peroxidase showed no consistent pooled effect. Risk-of-bias assessment using SYRCLE indicated predominantly unclear reporting for randomization, allocation concealment, and blinding, while attrition and reporting domains were mostly low-risk. Overall, brown macroalgal polyphenols show promising antioxidant effects in vivo, but substantial heterogeneity and incomplete methodological reporting limit certainty and preclude direct extrapolation to humans. Full article

► Show Figures

Figure 1

22 pages, 1993 KB

Open AccessReview

Roles and Mechanisms of Histone Deacetylases in Plant Abiotic Stress Responses

by Enyang Lv, Panfeng Yao, Jiangyuan Qin, Zigang Liu, Yan Fang, Zefeng Wu, Guoqiang Zheng, Junmei Cui and Jiaping Wei

Antioxidants 2026, 15(8), 960; https://doi.org/10.3390/antiox15080960 - 31 Jul 2026

Abstract

Histone deacetylases (HDACs) are key epigenetic enzymes governing lysine deacetylation. This modification is tightly coupled to cellular redox homeostasis and antioxidant signaling in plants. Plant HDACs are grouped into three subfamilies: RPD3/HDA1, SIR2, and plant-specific HD2. HDACs target both histone residues (e.g., H3K9 [...] Read more.

Histone deacetylases (HDACs) are key epigenetic enzymes governing lysine deacetylation. This modification is tightly coupled to cellular redox homeostasis and antioxidant signaling in plants. Plant HDACs are grouped into three subfamilies: RPD3/HDA1, SIR2, and plant-specific HD2. HDACs target both histone residues (e.g., H3K9 and H4K5) and a broad set of non-histone substrates (e.g., transcription factors and metabolic enzymes). Via coordinated chromatin remodeling and non-histone protein modification, HDACs integrate phytohormone signals, reactive oxygen species (ROS) bursts and NAD⁺ metabolic fluctuations to orchestrate plant abiotic stress responses, balancing antioxidant defense, redox equilibrium and normal growth. This review systematically sorts the divergent stress-response traits, substrate preferences and bidirectional regulatory logic of the three HDAC subfamilies; integrates chromatin-dependent and transcription factor-centered transcriptional branches; and summarizes crosstalk rules between HDAC-mediated deacetylation and other epigenetic marks. We further hierarchically clarify current research bottlenecks spanning basic mechanism dissection, multi-crop validation and field breeding transformation and propose targeted stratified research directions. We further construct a complete regulatory cascade linking environmental stimuli, ROS/ABA/NAD⁺ signals, HDAC activity and downstream antioxidant/stress gene expression, filling gaps in previous reviews that overlook redox-dependent HDAC functions. This mechanistic framework delivers integrated epigenetic and redox theoretical references for breeding stress-tolerant crops with reinforced antioxidant capacity. Full article

► Show Figures

Figure 1

23 pages, 6752 KB

Open AccessArticle

lncRNA1386.1/novel-miR0032-5p Axis Targets CAT Gene to Modulate Redox and Immune Reponses of Apis cerana Larvae to Ascosphaera apis Infection

by Xiaoxue Fan, Nian Fan, Kunze Li, Kaiyao Zhang, Xue Yang, Jiarun Yang, Jing Tian, Jianfeng Qiu, Qingwei Tan, Dafu Chen and Rui Guo

Antioxidants 2026, 15(8), 959; https://doi.org/10.3390/antiox15080959 - 31 Jul 2026

Abstract

Long non-coding RNAs (lncRNAs) participate in insect immune regulation, but their relationship with antioxidant responses during fungal infection remains unclear. Here, we examined a candidate regulatory relationship among lncRNA1386.1, novel-miR0032-5p, and the catalase gene (CAT) in Apis cerana worker larvae infected [...] Read more.

Long non-coding RNAs (lncRNAs) participate in insect immune regulation, but their relationship with antioxidant responses during fungal infection remains unclear. Here, we examined a candidate regulatory relationship among lncRNA1386.1, novel-miR0032-5p, and the catalase gene (CAT) in Apis cerana worker larvae infected with Ascosphaera apis. Dual-luciferase reporter assays showed that M-miR0032-5p reduced the activity of reporters containing the predicted miRNA response element within lncRNA1386.1 or CAT, whereas mutation of these sequences weakened or abolished the response. In infected larvae, lncRNA1386.1 silencing and novel-miR0032-5p overexpression reduced CAT transcript abundance and CAT protein concentration, and increased dihydroethidium (DHE) fluorescence intensity. These treatments were also accompanied by alterations in the transcript abundance of the host genes Dorsal1 and Relish and the fungal genes Chit3 and STE11-like. Novel-miR0032-5p inhibition generally produced opposite changes in CAT-related measurements, DHE fluorescence intensity, and the selected host and fungal transcripts. lncRNA1386.1 silencing was associated with increased larval survival, whereas novel-miR0032-5p inhibition was associated with a higher hazard of first visible external mycelial growth without significantly affecting survival. These findings support a negative regulatory role of novel-miR0032-5p in CAT expression and indicate that lncRNA1386.1 participates in a candidate shared miRNA-responsive regulatory relationship. This candidate regulatory relationship was associated with CAT-related antioxidant regulation, superoxide-associated DHE fluorescence, immune-related transcription, selected fungal transcriptional responses, and visible external mycelial growth during A. apis infection. Full article

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

► Show Figures

Figure 1

18 pages, 5512 KB

Open AccessArticle

Tylosin Removal Under Pb²⁺ Stress Using Kurthia gibsonii TYL-A1: Redox Adaptation and Transcriptomic Insights

by Ye Wang, Heshi Tian, Xiqing Zhang, Yuanquan Zhu, Lingcong Kong, Changlong Gou, Hongxia Ma, Xiuzhen Yu, Wenyan Yang and Yunhang Gao

Antioxidants 2026, 15(8), 958; https://doi.org/10.3390/antiox15080958 - 31 Jul 2026

Abstract

With the increasing prevalence of antibiotic–heavy metal co-contamination in agricultural wastewater, elucidating the antibiotic removal capacity of degrading bacteria under heavy metal stress, as well as their adaptive mechanisms, is of considerable theoretical significance and practical value. In this study, the highly efficient [...] Read more.

With the increasing prevalence of antibiotic–heavy metal co-contamination in agricultural wastewater, elucidating the antibiotic removal capacity of degrading bacteria under heavy metal stress, as well as their adaptive mechanisms, is of considerable theoretical significance and practical value. In this study, the highly efficient TYL-degrading strain TYL-A1 was selected as a model organism, and the effects of Pb²⁺ exposure on its TYL removal performance, oxidative stress response, cell surface characteristics, and transcriptional regulation were systematically investigated. The results showed that TYL removal remained above 85% after 72 h under a nominal Pb²⁺ concentration of 100 mg/L in the phosphate-containing MSM system. The phosphate may have reduced Pb²⁺ bioavailability. Nominal Pb²⁺ exposure increased the activities of superoxide dismutase (SOD) and catalase (CAT), accompanied by elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as a decrease in adenosine triphosphate (ATP) content. This indicates that the strain experienced pronounced oxidative stress and altered energy metabolism. Meanwhile, cell membrane permeability increased. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) analyses showed that the overall cellular morphology remained intact, whereas the membrane surface structure and related cellular components underwent adaptive changes. According to a transcriptomic analysis, the differentially expressed genes were mainly enriched in pathways associated with primary metabolism, transmembrane transport, ABC transporters, and two-component systems. In summary, strain TYL-A1 maintained high TYL removal performance under the tested nominal Pb²⁺ concentrations in the present phosphate-containing culture system, suggesting its potential applicability in the bioremediation of water bodies co-contaminated with antibiotics and heavy metals. Full article

► Show Figures

Figure 1

20 pages, 3072 KB

Open AccessArticle

Downregulation of the L-PGDS/15d-PGJ2 Pathway Is Associated with Manganese-Induced Neuroinflammation and Cognitive Impairment Involving C/EBPβ and MMP9

by Junrou Zhang, Kai Xu, Yan Ye, Junxiang Ma, Li Chen, Tian Chen and Piye Niu

Antioxidants 2026, 15(8), 957; https://doi.org/10.3390/antiox15080957 - 31 Jul 2026

Abstract

Excessive manganese (Mn) exposure is associated with neuroinflammation and cognitive impairment, yet the contribution of endogenous pro-resolving pathways to Mn neurotoxicity remains incompletely understood. Here, we examined the involvement of the lipocalin-type prostaglandin D synthase (L-PGDS)/15-deoxy-Δ^12,14-prostaglandin J2 (15d-PGJ2) pathway using Mn-treated [...] Read more.

Excessive manganese (Mn) exposure is associated with neuroinflammation and cognitive impairment, yet the contribution of endogenous pro-resolving pathways to Mn neurotoxicity remains incompletely understood. Here, we examined the involvement of the lipocalin-type prostaglandin D synthase (L-PGDS)/15-deoxy-Δ^12,14-prostaglandin J2 (15d-PGJ2) pathway using Mn-treated male C57BL/6J mice, BV2 microglia, and SH-SY5Y neurons, together with data from occupationally Mn-exposed workers (cross-sectional, hypothesis-generating). In the occupational cohort, circulating 15d-PGJ2 levels and L-PGDS expression were reduced following Mn exposure, consistent with the experimental findings. PPI network analysis and promoter prediction highlighted C/EBPβ and MMP9 as potential mediators of Mn-induced neuroinflammatory responses. Consistent with these observations, Mn exposure increased C/EBPβ and MMP9 expression, promoted M1 microglial polarization, elevated ROS production, and aggravated neuronal injury in a microglia–neuron co-culture system. Knocking down either C/EBPβ or MMP9 attenuated inflammatory activation and oxidative stress and reduced neuronal damage. Administration of exogenous 15d-PGJ2 suppressed Mn-induced increases in C/EBPβ and MMP9, alleviated inflammatory and oxidative responses, and partially ameliorated cognitive impairment in Mn-exposed mice. Transcriptomic analyses further showed that 15d-PGJ2 counteracted a substantial proportion of Mn-induced transcriptional alterations, particularly those related to inflammatory and neurodevelopmental processes. In addition, Ptgds knockdown reduced endogenous 15d-PGJ2 production and increased MMP9 expression, whereas exogenous 15d-PGJ2 largely reversed these changes. Together, these findings support the involvement of L-PGDS/15d-PGJ2 pathway dysregulation in Mn-induced neuroinflammation and suggest that restoration of 15d-PGJ2 signaling may represent a potential therapeutic approach for Mn-associated neurotoxicity. Full article

(This article belongs to the Special Issue Advances in Redox Biochemistry of Cognitive Impairment Pathogenesis and Treatment)

► Show Figures

Figure 1

17 pages, 2984 KB

Open AccessArticle

AGEs–RAGE Axis and Mitochondrial-Derived Peptides in Advanced Chronic Kidney Disease: Interconnected Pathways Beyond Inflammation and Nutrition

by Mohamed E. Suliman, Awahan Rahman, Abdul-Rashid Qureshi, Peter Barany, Peter Stenvinkel, Karolina Kublickiene and Bengt Lindholm

Antioxidants 2026, 15(8), 956; https://doi.org/10.3390/antiox15080956 - 30 Jul 2026

Abstract

Background. Chronic kidney disease [CKD] is characterized by increased glycoxidative stress, inflammation, and mitochondrial dysfunction. Advanced glycation end-products [AGEs] and their receptor [RAGE] mediate glycoxidative stress, whereas mitochondrial-derived peptides [MDPs], including humanin [HN], MOTS-c, and humanin-like 1 [HN-L1], regulate mitochondrial stress responses. We [...] Read more.

Background. Chronic kidney disease [CKD] is characterized by increased glycoxidative stress, inflammation, and mitochondrial dysfunction. Advanced glycation end-products [AGEs] and their receptor [RAGE] mediate glycoxidative stress, whereas mitochondrial-derived peptides [MDPs], including humanin [HN], MOTS-c, and humanin-like 1 [HN-L1], regulate mitochondrial stress responses. We investigated links between AGE–RAGE activation and mitochondrial signaling in CKD. Methods. Serum AGEs, soluble RAGE isoforms, and MDPs were measured by ELISA in 160 adults with kidney failure undergoing living-donor kidney transplantation and in 80 controls, Results. CKD patients showed higher AGEs and esRAGE, lower AGEs/sRAGE ratios, and reduced MDPs. AGEs correlated positively with sRAGE, cRAGE, and HN, while MOTS-c was inversely associated with AGEs and the AGEs/sRAGE ratio. In multivariable analyses, HN remained independently associated with AGEs, sRAGE, and the AGEs/sRAGE ratio, whereas MOTS-c showed an inverse association with the AGEs/sRAGE ratio. CRP was associated with the AGEs/sRAGE ratio while PEW showed no associations with AGEs–RAGE components or MDP. Conclusions. CKD is characterized by increased glycoxidative stress and reduced MDPs, reflecting altered mitochondrial stress signaling. AGEs–RAGE and MDPs are biologically linked, suggesting partially overlapping but distinct pathophysiological pathways. Full article

(This article belongs to the Special Issue Advances in Oxidative Stress, Mitochondrial Dysfunction and Antioxidant Therapies in Endocrine and Metabolic Disorders)

► Show Figures

Figure 1

23 pages, 21263 KB

Open AccessArticle

MMP8 Promotes NETosis in Gestational Diabetes Mellitus

by Nan Li, Tong Zhou, Kun Yang, Wen-Jun Yang, Gui Yang, Yong-Wei Duan, Ying Yang, Huan-Yu Liu and Song-Mei Liu

Antioxidants 2026, 15(8), 955; https://doi.org/10.3390/antiox15080955 - 30 Jul 2026

Abstract

Background: Neutrophil extracellular traps (NETs) have been known to be involved in the gestational diabetes mellitus (GDM), but the underlying role remains poorly understood. Methods: We conducted an integrated analysis of bulk RNA-seq data, single-cell transcriptomic sequencing (scRNA-seq) data, clinical laboratory findings, and [...] Read more.

Background: Neutrophil extracellular traps (NETs) have been known to be involved in the gestational diabetes mellitus (GDM), but the underlying role remains poorly understood. Methods: We conducted an integrated analysis of bulk RNA-seq data, single-cell transcriptomic sequencing (scRNA-seq) data, clinical laboratory findings, and cell models to identify hub genes linked to NET formation (NETosis) and to elucidate how NETs contribute to placental injury in GDM. Results: We found that circulating NET levels were increased in pregnant women with GDM both under fasting conditions and following an oral glucose tolerance test (OGTT). Primary neutrophils isolated from healthy pregnant women produced more NETs upon high-glucose stimulation in vitro. The mRNA expression of PADI4, a key regulator of NETosis, was upregulated and positively correlated with MMP8 mRNA in patients with GDM. Inhibition of MMP8 suppressed intracellular reactive oxygen species (ROS) generation and attenuated NETosis in neutrophils. scRNA-seq analysis of placental tissues from patients with GDM identified a neutrophil subset with higher PADI4 expression. In vitro stimulation with NETs induced functional impairment of HTR8/SVneo cells. Conclusions: We uncovered that MMP8, a novel NETosis-promoting molecule, is a promising target for GDM intervention. Full article

► Show Figures

Figure 1

Journal Description

Antioxidants

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI