Antioxidants

30 pages, 1345 KB

Open AccessReview

Biology of HDL: From Structural Heterogeneity to Dysfunctional Remodeling in Cardiovascular Disease and Comorbidities

by Yihang Cai, Kehan Li, Huibo Ma, Jianqiang Wu and Yuehong Zheng

Antioxidants 2026, 15(7), 864; https://doi.org/10.3390/antiox15070864 - 10 Jul 2026

The pathogenesis of cardiovascular diseases (CVDs) is intimately linked to cholesterol dysregulation. While high-density lipoprotein cholesterol (HDL-C) is classically considered cardioprotective, contemporary epidemiological evidence reveals a noncausal, often U-shaped, relationship with CVD risk. Static measurements of HDL-C obscure the structural and functional heterogeneity [...] Read more.

The pathogenesis of cardiovascular diseases (CVDs) is intimately linked to cholesterol dysregulation. While high-density lipoprotein cholesterol (HDL-C) is classically considered cardioprotective, contemporary epidemiological evidence reveals a noncausal, often U-shaped, relationship with CVD risk. Static measurements of HDL-C obscure the structural and functional heterogeneity of circulating HDL particles. Under pathological stress, HDL undergoes extensive structural remodeling into dysfunctional HDL, thereby losing its vasculoprotective properties and instead mediating proatherogenic and proinflammatory responses. This review critically evaluates the biogenesis, maturation, and metabolic trajectory of HDL. By integrating recent advancements in proteomics and lipidomics, we map the intricate compositional shifts within HDL subpopulations and clarify the regulatory roles of HDL-associated microRNAs in intercellular communication. We investigate the specific drivers of HDL dysfunction, which is often exacerbated by comorbidities such as diabetes and chronic kidney disease. Furthermore, we outline the methodological transition from automated homogeneous HDL-C quantification to multidimensional profiling. Shifting the clinical focus from HDL quantity to functional quality resolves the HDL-C paradox, helping to drive the development of precision lipidology and targeted therapies to reverse HDL dysfunction in CVDs. Full article

(This article belongs to the Section Aberrant Oxidation of Biomolecules)

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28 pages, 1196 KB

Open AccessReview

Mechanistic Insights into Phytocompounds for Vitiligo Therapy: Current Evidence and Future Opportunities

by Rethabile Banda-Lesole, Ipeleng Kopano Rosinah Kgosiemang and Tshepiso Jan Makhafola

Antioxidants 2026, 15(7), 863; https://doi.org/10.3390/antiox15070863 - 10 Jul 2026

Abstract

Vitiligo is a multifactorial depigmentation disorder involving complex interactions among oxidative stress, immune dysregulation, inflammatory signaling, and programmed cell death pathways, which act as a central driver of melanocyte dysfunction and loss, interacting with immune-mediated cytotoxicity and intrinsic cellular susceptibility. Excessive reactive oxygen [...] Read more.

Vitiligo is a multifactorial depigmentation disorder involving complex interactions among oxidative stress, immune dysregulation, inflammatory signaling, and programmed cell death pathways, which act as a central driver of melanocyte dysfunction and loss, interacting with immune-mediated cytotoxicity and intrinsic cellular susceptibility. Excessive reactive oxygen species (ROS) disrupt mitochondrial integrity, impair redox homeostasis, suppress microphthalmia-associated transcription factor (MITF)-dependent melanogenesis, and induce melanocyte apoptosis. Concomitant dysfunction of the nuclear factor erythroid 2-related factor 2 (NRF2)/antioxidant response element (ARE) axis further exacerbates oxidative injury by limiting endogenous antioxidant capacity. Current therapeutic approaches, including corticosteroids, phototherapy, and targeted immunomodulators, achieve partial repigmentation but do not adequately resolve melanocyte-intrinsic redox imbalance. This structured narrative review comprehensively integrates mechanistic and translational evidence to define phytocompounds as redox-active, multi-target modulators in vitiligo. Plant-derived polyphenols, flavonoids, terpenoids, and related metabolites are shown to attenuate ROS accumulation, preserve mitochondrial function, activate NRF2-dependent antioxidant signaling, and restore MITF-mediated expression of tyrosinase and associated melanogenic enzymes. Furthermore, coordinated modulation of MAPK, PI3K/Akt, and JAK/STAT pathways highlights their capacity to regulate immune–oxidative crosstalk and promote melanocyte survival. Despite promising preclinical and emerging clinical evidence of repigmentation efficacy, translational progress remains limited by poor phytochemical standardization, insufficient transcriptional and proteomic validation, suboptimal stability and dermal bioavailability, and a lack of rigorously designed clinical trials. Collectively, this review provides a mechanistic framework linking redox dysregulation to melanocyte failure and positions phytocompounds as rational candidates for adjunctive or stand-alone antioxidant-based therapies, while defining critical priorities for clinical translation. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection and Skin Disease)

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20 pages, 2799 KB

Open AccessArticle

Gene- and Isoform-Level Responses to Extreme Acidic pH Stress in an Emerging Marine Invertebrate Model Organism Litoditis marina

by Beining Xue, Pengchi Zhang, Hanwen Yang and Liusuo Zhang

Antioxidants 2026, 15(7), 862; https://doi.org/10.3390/antiox15070862 - 9 Jul 2026

Abstract

Ocean acidification poses a critical threat to marine invertebrate survival and diversification, yet the post-transcriptional regulatory mechanisms underlying acid stress responses remain poorly understood. Here, we employed Oxford Nanopore long-read RNA sequencing to systematically characterize transcriptional and post-transcriptional responses to acidic pH stresses [...] Read more.

Ocean acidification poses a critical threat to marine invertebrate survival and diversification, yet the post-transcriptional regulatory mechanisms underlying acid stress responses remain poorly understood. Here, we employed Oxford Nanopore long-read RNA sequencing to systematically characterize transcriptional and post-transcriptional responses to acidic pH stresses in the marine nematode Litoditis marina. Our analysis revealed 912 upregulated and 728 downregulated genes enriched in autophagy, fatty acid metabolism, and peroxisome activation, alongside 327 differential alternative splicing events and 1512 transcripts with significant usage changes under severe acidic pH stress. By integrating weighted gene co-expression network analysis with databases such as WormExp2, we found that acidic pH stress response exhibited resemblance to oxidative stress response. Specifically, we identified genes involved in the oxidative stress response, such as gpx-1, cyp-13A11, trxr-1, cyc-1, and key regulators, including hlh-30/TFEB. Genes such as gpx-1, trxr-1, and cyp-23A1 might protect L. marina from oxidative stress under acidic pH. Moreover, several ferroptosis-related genes, such as gpx-5, fat-2, and smf-1, might render L. marina vulnerable to acidic pH stress. Among the genes with splicing changes, we identified oxidative stress responding genes such as sod-4, prx-2, coq-2, coq-3, prx-10, ctl-2, gst-7, trx-1, mdt-15, and fat-2. Additionally, we discovered the preference for proximal 3′ UTR under acidic pH stress. Genes related to ferroptosis, including cyp-23A1, C07E3.9/PLA2G1B, and C53D5.5/GGT1, exhibited differential 3′ UTR usage under acidic pH stress. Our findings shift the focus from traditional gene-centric analyses to capturing the full breadth of post-transcriptional diversity, providing novel insights into post-transcriptional gene regulation in marine metazoans under environmental stress, as well as revealing that alleviating oxidative stress might increase resistance to acid pH stress. Full article

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

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17 pages, 794 KB

Open AccessArticle

Urinary TBARS as a Non-Invasive Proxy of Plasma Lipid Peroxidation in Essential Hypertension: A Translational Study on Vascular Oxidative–Inflammatory Burden

by Antón Cruces-Sande, Néstor Vázquez-Agra, Óscar Seoane-Casqueiro, Emma López-Prado, Estefanía Méndez-Álvarez, Ramón Soto-Otero, Antonio Pose-Reino and Álvaro Hermida-Ameijeiras

Antioxidants 2026, 15(7), 861; https://doi.org/10.3390/antiox15070861 - 9 Jul 2026

Abstract

Background/Objectives: Lipid peroxidation is a relevant oxidative–inflammatory mechanism in essential hypertension and cardiovascular disease. Plasma thiobarbituric acid reactive substances (TBARS), commonly reported as malondialdehyde-equivalent values, provide an operational index of lipid peroxidation-related aldehydic reactivity, but blood-based assessment is limited by venipuncture and preanalytical [...] Read more.

Background/Objectives: Lipid peroxidation is a relevant oxidative–inflammatory mechanism in essential hypertension and cardiovascular disease. Plasma thiobarbituric acid reactive substances (TBARS), commonly reported as malondialdehyde-equivalent values, provide an operational index of lipid peroxidation-related aldehydic reactivity, but blood-based assessment is limited by venipuncture and preanalytical handling requirements. Urine is an attractive non-invasive matrix for redox biomarker development, although whether urinary TBARS reflect plasma lipid peroxidation in hypertensive patients remains insufficiently characterized. This study aimed to evaluate whether matrix-specific normalization—total cholesterol for plasma TBARS and creatinine for urinary TBARS—reveals a measurable intra-individual relationship between these matrices in essential hypertension. Methods: In this paired observational study, plasma and urine samples were obtained from 39 treated patients with essential hypertension under standardized fasting conditions. TBARS were quantified using a colorimetric thiobarbituric acid reaction assay. Plasma TBARS were normalized to total cholesterol and expressed as TBARSp, while urinary TBARS were normalized to creatinine and expressed as TBARSu. Associations were assessed using Spearman’s rank correlation, exploratory receiver operating characteristic (ROC) analyses based on internally derived plasma TBARS percentile thresholds, and Bayesian bootstrap inference. Results: Cholesterol-normalized plasma TBARS and creatinine-normalized urinary TBARS showed a moderate-to-strong positive monotonic association (Spearman’s ρ = 0.717, p < 0.001). Bayesian bootstrap analysis supported this relationship, with a 95% credible interval of 0.57–0.83 and a Bayes factor > 300 for ρ ≥ 0.5. Urinary TBARS showed exploratory within-cohort discriminatory capacity for identifying elevated plasma TBARS using internally derived thresholds, with an AUC of 0.892 for the median-based classification. Conclusions: Creatinine-normalized urinary TBARS showed a moderate-to-strong association with cholesterol-normalized plasma TBARS in treated essential hypertension. These findings provide hypothesis-generating paired-sample evidence that urinary TBARS may serve as a low-burden, non-invasive proxy of plasma lipid peroxidation-related redox alterations. Further validation in larger and clinically diverse cohorts, ideally including more specific lipid peroxidation markers and renal-function-aware analyses, is required to define their translational and clinical utility. Full article

(This article belongs to the Special Issue Redox Biomarkers in Inflammatory Diseases)

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20 pages, 1932 KB

Open AccessReview

Ferroptosis Resistance: Redundant Antioxidant Networks Are a Barrier to Cancer Therapy

by Birandra K. Sinha

Antioxidants 2026, 15(7), 860; https://doi.org/10.3390/antiox15070860 - 9 Jul 2026

Abstract

Ferroptosis is an iron-dependent, lipid peroxidation-driven form of regulated cell death that has emerged as a promising strategy for targeting therapy-resistant cancers. However, both intrinsic and acquired resistance to ferroptosis-inducing agents (FINs) limit their clinical efficacy. Here, we propose an integrated framework in [...] Read more.

Ferroptosis is an iron-dependent, lipid peroxidation-driven form of regulated cell death that has emerged as a promising strategy for targeting therapy-resistant cancers. However, both intrinsic and acquired resistance to ferroptosis-inducing agents (FINs) limit their clinical efficacy. Here, we propose an integrated framework in which ferroptosis resistance arises from coordinated redox, metabolic, lipid, iron, and transport adaptations that collectively suppress lipid peroxidation and promote tumor survival. Central to this network is the cysteine–glutathione–GPX4 axis, supported by parallel GPX4-independent systems including FSP1–CoQ10, DHODH–CoQ10, GCH1–BH4, and NQO1–NADPH pathways. These antioxidant systems are reinforced by NRF2-driven transcriptional programs, iron sequestration mechanisms, lipid remodeling that reduces polyunsaturated fatty acid availability, and ATP-binding cassette (ABC) transporters that regulate drug and glutathione flux. Tumor heterogeneity further enhances ferroptosis resistance by generating metabolically distinct cellular subpopulations that differ in their susceptibility to lipid peroxidation. We discuss emerging therapeutic strategies designed to overcome these coordinated defense mechanisms, including simultaneous targeting of GPX4 and FSP1, metabolic reprogramming, iron-directed therapies, and nanoparticle-based delivery systems. Collectively, these observations support a systems-level model in which durable ferroptosis-based cancer therapy will require disruption of multiple interconnected resistance mechanisms rather than inhibition of a single molecular target. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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17 pages, 1826 KB

Open AccessArticle

Effect of Ammonia on Escherichia coli Growth and Aerobic Respiration: The Role of Cytochrome bd-II

by Francesca Giordano, Martina Roberta Nastasi, Vitaliy B. Borisov and Elena Forte

Antioxidants 2026, 15(7), 859; https://doi.org/10.3390/antiox15070859 - 9 Jul 2026

Abstract

Bacterial terminal oxidases are essential for growth and may provide protection against environmental stressors. Bacteria often have to cope with ammonia, which, although an essential nutrient, is toxic at high concentrations. Here, we studied the influence of ammonia on the cell growth of [...] Read more.

Bacterial terminal oxidases are essential for growth and may provide protection against environmental stressors. Bacteria often have to cope with ammonia, which, although an essential nutrient, is toxic at high concentrations. Here, we studied the influence of ammonia on the cell growth of three different Escherichia coli respiratory mutants, each possessing a single terminal oxidase: cytochrome bd-I, cytochrome bd-II, or cytochrome bo₃. We also investigated the effect of ammonia on O₂ consumption in cytochrome bd-II-only cells and membranes, as well as in the isolated bd-II enzyme. Using microcalorimetry, spectrophotometry and high-resolution respirometry, the following new results were obtained: (i) At pH 8.3, the addition of ammonia to both bd-I-only and bd-II-only cell cultures has virtually no effect on growth. In contrast, the growth of bo₃-only cells is significantly impaired. (ii) The addition of ammonia to bd-II-only intact cells at pH 8.3 not only fails to inhibit their respiration but also accelerates O₂ consumption. The same is observed with bd-II-only isolated membranes and detergent-solubilized bd-II enzyme. The maximum increase in cytochrome bd-II O₂ consumption rate is approximately 150%. Physiological aspects of the findings are discussed, and molecular mechanisms for ammonia-induced acceleration of O₂ consumption by cytochrome bd-II are suggested. Full article

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

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19 pages, 2908 KB

Open AccessArticle

N-Acetylcysteine Attenuates Oxidative Stress and Preserves Red Blood Cell Quality During Whole Blood Storage

by Sonia Eligini, Lisa Brocca, Alice Mallia, Arianna Valeriano, Erica Gianazza and Cristina Banfi

Antioxidants 2026, 15(7), 858; https://doi.org/10.3390/antiox15070858 - 8 Jul 2026

Abstract

Whole blood (WB) storage induces biochemical and biomechanical alterations that may compromise red blood cell (RBC) quality. Since oxidative stress is a major driver of storage lesions, we investigated whether N-acetylcysteine (NAC) could attenuate these changes during refrigerated storage. WB from healthy donors [...] Read more.

Whole blood (WB) storage induces biochemical and biomechanical alterations that may compromise red blood cell (RBC) quality. Since oxidative stress is a major driver of storage lesions, we investigated whether N-acetylcysteine (NAC) could attenuate these changes during refrigerated storage. WB from healthy donors was stored at 4 °C for 42 days with or without NAC, added either once at baseline or every 10 days. Plasma albumin proteoforms were assessed by liquid chromatography–mass spectrometry, free hemoglobin species by spectrophotometry, plasma proteomic changes by proximity extension assay, and RBC hemorheological properties by LORRCA analysis. Storage decreased reduced albumin (HSA-SH) and increased oxidized albumin (HSA-Cys), indicating plasma oxidation. Free oxyhemoglobin, deoxyhemoglobin, and methemoglobin increased, consistent with hemoglobin oxidation and hemolysis. Storage also induced plasma proteomic alterations and impaired RBC osmotic and deformability parameters. NAC preserved albumin redox status, limited free hemoglobin accumulation, and attenuated storage-induced proteomic changes. Moreover, NAC partially preserved RBC osmotic and rheological properties, particularly parameters related to osmotic fragility and hydration. No clear advantage of 20 mM over 10 mM NAC was observed. Overall, NAC attenuated oxidative and functional alterations associated with refrigerated whole blood storage, supporting further investigation of antioxidant supplementation as a strategy to mitigate storage lesions under ex vivo conditions. Full article

(This article belongs to the Special Issue Advanced Bioanalytical Techniques in Antioxidant and Oxidative Stress Research)

24 pages, 13153 KB

Open AccessArticle

Polyphenolic Imidazopyridines as Multifunctional Modulators of Oxidative Stress, Metal Dyshomeostasis, and β_1-42 Amyloid Aggregation in an In Vitro Model of Alzheimer’s Disease

by Lidia Ciccone, Giovanni Petrarolo, Ilaria D’Agostino, Fabio Scianò, Bianca Laura Bernardoni, Manuela Leri, Jihyae Ann, Susanna Nencetti, Jeewoo Lee, Monica Bucciantini and Concettina La Motta

Antioxidants 2026, 15(7), 857; https://doi.org/10.3390/antiox15070857 - 8 Jul 2026

Abstract

Alzheimer’s disease (AD) involves oxidative stress, metal dyshomeostasis, and toxic oligomers of the amyloid-β peptide (Aβ_1-42), calling for multifunctional agents. We investigated a panel of imidazo[1,2-a]pyridines bearing catechol or resorcinol motifs previously designed as SIRT1-activating agents. Their antioxidant profile [...] Read more.

Alzheimer’s disease (AD) involves oxidative stress, metal dyshomeostasis, and toxic oligomers of the amyloid-β peptide (Aβ_1-42), calling for multifunctional agents. We investigated a panel of imidazo[1,2-a]pyridines bearing catechol or resorcinol motifs previously designed as SIRT1-activating agents. Their antioxidant profile was evaluated using in vitro DPPH and ABTS assays, which revealed promising radical scavenging activities, and TBARS assays on rat brain homogenates showing inhibition of lipid peroxidation, strictly dependent on the phenolic pattern. UV–Vis studies revealed metal-binding properties, particularly Cu²⁺ and Fe²⁺ interactions. In Aβ_1-42 aggregation assays, the most active derivatives appeared to promote fibril maturation and the growth of large, ThT-low aggregates with distinct morphological features observed by TEM. Notably, Aβ_1-42 aggregates generated in the presence of these compounds exhibited reduced cytotoxicity, preserved cell viability, and induced lower ROS levels in RA-differentiated SH-SY5Y cells compared to aggregates formed in their absence. Imaging and FRET analyses further indicated reduced formation of membrane-binding toxic species. Overall, our data suggest that polyphenolic imidazo[1,2-a]pyridines can remodel Aβ_1-42 aggregation, redirecting it toward structurally distinct and less toxic assemblies, while also counteracting oxidative and metal-associated damage. These findings highlight their potential as multifunctional agents capable of addressing several pathological hallmarks of AD. Full article

(This article belongs to the Special Issue Oxidative Stress as a Therapeutic Target of Alzheimer’s Disease—2nd Edition)

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23 pages, 17730 KB

Open AccessArticle

Dihydromyricetin Alleviates Fermented Rapeseed Meal-Induced Intestinal Injury in Chinese Soft-Shelled Turtle (Pelodiscus sinensis): Insights from Growth, Antioxidant, Inflammatory, Transcriptomic and Metabolomic Assessments

by Wenshu Liu, Lun Chen, Wencai Liu, Jingjing Lu, Yuzhu Wang, Xiaoze Guo, Lingya Li, Xu Han, Chuang Mei, Siming Li and Zirui Wang

Antioxidants 2026, 15(7), 856; https://doi.org/10.3390/antiox15070856 - 8 Jul 2026

Abstract

This study was designed to assess the protective efficacy of dihydromyricetin (DHM) against intestinal injury in Chinese soft-shelled turtles (Pelodiscus sinensis) caused by partial replacement of fishmeal (FM) with fermented rapeseed meal (FRM), and to uncover the molecular mechanisms involved. Turtles [...] Read more.

This study was designed to assess the protective efficacy of dihydromyricetin (DHM) against intestinal injury in Chinese soft-shelled turtles (Pelodiscus sinensis) caused by partial replacement of fishmeal (FM) with fermented rapeseed meal (FRM), and to uncover the molecular mechanisms involved. Turtles were fed an FM-based control diet, an FRM-substituted diet, or FRM diets supplemented with DHM at 0.5‰ (DHMT1), 1.0‰ (DHMT2) or 2.0‰ (DHMT3) for 8 weeks. Growth performance, digestive enzyme activities, antioxidant parameters, inflammatory cytokines, and intestinal histomorphology were assessed, and intestinal transcriptomics and metabolomics were also performed. FRM replacement significantly improved growth performance; however, this beneficial effect was accompanied by notable intestinal mucosal oxidative damage, as evidenced by decreased villus height, increased lumen space, and lamina propria edema, along with elevated pro-inflammatory cytokines (IL-1β and TNF-α) and MDA content, alongside reduced GSH and CAT activities. DHM supplementation dose-dependently ameliorated these adverse effects by restoring mucosal integrity, digestive enzyme activities, redox homeostasis, and inflammatory balance, ultimately improving growth performance. Transcriptomic KEGG analysis revealed that DHM enriched pathways related to glycerophospholipid metabolism, glutathione metabolism, drug metabolis-cytochrome P450, and polyunsaturated fatty acid metabolism. Metabolomics further confirmed dose-dependent remodeling of phospholipids and bile acids. Integrated omics demonstrated that DHM likely regulates detoxification, anti-inflammatory, membrane repair, and antioxidant pathways. In conclusion, DHM demonstrates a protective effect against FRM-induced intestinal mucosal oxidative damage in P. sinensis, which may be mediated by a synergistic combination of enhanced detoxification, anti-inflammatory modulation, restoration of phospholipid membrane integrity, and reinforcement of antioxidant defenses. Full article

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22 pages, 3985 KB

Open AccessArticle

Safflower Extract Ameliorates Cisplatin-Induced Acute Kidney Injury by Regulating Microbiota-Metabolic-Redox Nexus and PI3K–Akt/Nrf2 Pathway

by Yue Chang, Yanzhuo Song, Naveed Ahmad, Chao Song, Yuhang Chu, Yuru Zhang, Lufei Feng, Wei Wei, Min Zhang and Xiuming Liu

Antioxidants 2026, 15(7), 855; https://doi.org/10.3390/antiox15070855 - 7 Jul 2026

Abstract

Cisplatin-induced acute kidney injury (AKI) remains a dose-limiting complication in cancer chemotherapy with restricted preventive measures. Carthamus tinctorius L. (safflower) is known to exhibit effective antioxidant and anti-inflammatory properties; however its potential in renoprotective mechanisms remains poorly understood. The present study utilized a [...] Read more.

Cisplatin-induced acute kidney injury (AKI) remains a dose-limiting complication in cancer chemotherapy with restricted preventive measures. Carthamus tinctorius L. (safflower) is known to exhibit effective antioxidant and anti-inflammatory properties; however its potential in renoprotective mechanisms remains poorly understood. The present study utilized a cisplatin-induced AKI mouse model to evaluate the renoprotective potential of CT (Carthamus tinctorius) extract. Integrated multi-omics along with in silico and in vivo approaches were used to elucidate the underlying mechanisms of action. The results initially demonstrated a rich phytochemical profile of CT extract characterized by abundant polysaccharides and flavonoids, with Hydroxysafflor Yellow A as a dominant bioactive constituent. In a cisplatin-induced acute kidney injury (AKI) mouse model, CT extract noticeably ameliorated the abnormalities of renal injury, as suggested by improved histopathology, reduced serum creatinine and BUN levels, and regulation of redox homeostasis. Metabolically, CT extract partially reversed AKI-associated disturbances by affecting 21 key metabolites, likely associated with histidine and alanine-aspartate-glutamate biosynthesis, and modulating amino acid and energy metabolism pathways. Concurrently, CT extract improved gut microbial homeostasis, increasing microbial diversity, normalizing the Firmicutes/Bacteroidota ratio, suppressing pathogens, and enriching beneficial Ligilactobacillus. Network pharmacology and molecular docking identified AKT1, RELA, MAPK, and TP53 as central targets of core compounds (rutin and kaempferol derivatives), apparently targeting the PI3K-AKT and RELA (NF-kappaB) hubs. These results suggested that the renoprotective effects of CT extract are associated with transcriptional upregulation of the PI3K/Akt/Nrf2 pathway-related genes, increased expression of antioxidant genes (Ho-1, Sod1), and reduced expression of pro-inflammatory mediators (RelA, Cdk2) in the cisplatin-induced AKI mouse model. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Sources with Antioxidant and Anti-Inflammatory Potential)

15 pages, 7192 KB

Open AccessArticle

Promoter Hypermethylation Is Associated with Reduced Nrf2 and Antioxidant Enzyme Expression in Mandibular Condylar Cartilage in Mice

by Hisano Ujiie, Hiroyuki Kanzaki, Mao Katayama, Tomomi Ida, Syunnosuke Tohyama, Miho Shimoyama, Yuta Katsumata, Chihiro Arai, Misao Ishikawa and Hiroshi Tomonari

Antioxidants 2026, 15(7), 854; https://doi.org/10.3390/antiox15070854 - 6 Jul 2026

Abstract

Mandibular condylar cartilage (MCC) exhibits greater susceptibility to mechanical stress-induced degeneration than tibial articular cartilage (TAC). This study investigated whether differential epigenetic regulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant responses, is associated with distinct antioxidant capacities [...] Read more.

Mandibular condylar cartilage (MCC) exhibits greater susceptibility to mechanical stress-induced degeneration than tibial articular cartilage (TAC). This study investigated whether differential epigenetic regulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant responses, is associated with distinct antioxidant capacities between these cartilage types. Cartilage tissues from 5-week-old male ICR mice (n = 16 for gene analyses, n = 8 for protein analyses) were obtained using laser microdissection. Gene and protein expression was analyzed by microarray, real-time RT-PCR, and immunohistochemistry. DNA methylation of the Nrf2 promoter was evaluated using pyrosequencing and high-resolution melting analysis. Nrf2 expression in MCC was approximately 1/10 that in TAC at mRNA level and only 5% at protein level. Downstream antioxidant enzymes (NQO1, G6PD, HO-1) showed significantly reduced expression in MCC. Oxidative DNA damage marker 8-OHdG was significantly elevated in MCC compared to TAC (20.0% vs. 10.7%, p < 0.05). The Nrf2 promoter region showed higher DNA methylation levels in MCC, confirmed by high-resolution melting analysis. Higher Nrf2 promoter methylation in MCC is associated with reduced antioxidant capacity and elevated oxidative damage. This epigenetic–antioxidant relationship may contribute to MCC’s vulnerability to mechanical stress-induced degeneration and represents a potential therapeutic target for temporomandibular joint disorders. Full article

(This article belongs to the Special Issue Oxidative Stress in Osteoclast Metabolism: Implications for Bone Disease Treatment)

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43 pages, 23995 KB

Open AccessReview

Redox Regulation of Plant–Root-Knot Nematode Interactions: From ROS-Mediated Immunity to Sustainable Resistance

by Jung-Wook Yang, Ho Soo Kim and Yun-Hee Kim

Antioxidants 2026, 15(7), 853; https://doi.org/10.3390/antiox15070853 - 6 Jul 2026

Abstract

Root-knot nematodes (RKNs; Meloidogyne spp.) are among the most destructive plant parasites, causing severe yield losses in diverse crops. Reactive oxygen species (ROS), particularly superoxide radicals (O₂•⁻) and hydrogen peroxide (H₂O₂), are central regulators of [...] Read more.

Root-knot nematodes (RKNs; Meloidogyne spp.) are among the most destructive plant parasites, causing severe yield losses in diverse crops. Reactive oxygen species (ROS), particularly superoxide radicals (O₂•⁻) and hydrogen peroxide (H₂O₂), are central regulators of plant–RKN interactions. This review synthesizes current molecular, biochemical, genetic, transcriptomic, and translational evidence showing that the outcome of infection is determined by the spatiotemporal regulation of H₂O₂ rather than by ROS abundance alone. In resistant interactions, nematode perception activates PTI-associated signaling through selected cell-surface receptor complexes, including some BAK1/SERK3-associated pathways, together with BIK1, Ca²⁺ signaling, and RBOHD/F, generating a sustained oxidative activity associated with salicylic acid-dependent immune signaling and reduced H₂O₂-scavenging capacity and coupled to hypersensitive response, lignin and callose deposition, and feeding site restriction. In susceptible interactions, RKNs deploy ROS-targeting effectors such as Mi-CRT, MjTTL5, CATLe, Mj-NEROSs, and CMII to suppress ROS production, enhance antioxidant scavenging, or weaken SA-dependent defense. Evidence from a cyst-nematode system suggests that RBOH-derived ROS can restrict excessive cell death around syncytia; whether an analogous lower-redox requirement exists in RKN-induced giant cells remains unresolved. Finally, redox-based strategies, including CRISPR/Cas editing, host-induced gene silencing, chemical priming, and biocontrol, are discussed as promising approaches for durable and sustainable nematode resistance. Full article

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

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28 pages, 12762 KB

Open AccessArticle

Omega-3 Fatty Acids Attenuate Neuropathic Pain by Modulating Ferroptotic Stress, Selenoamino Acid Metabolism, and Lipid Remodeling

by Viet H. Dinh, Magda Descorbeth, Francis Zamora, Jo-Wen Liu, Cono Badalamenti, Salvador Soriano, Johnny D. Figueroa, Marino De León and Alfonso M. Durán

Antioxidants 2026, 15(7), 852; https://doi.org/10.3390/antiox15070852 - 6 Jul 2026

Abstract

Neuropathic pain (NP) arises from diverse conditions, including peripheral nerve injury, spinal cord injury (SCI), and painful diabetic neuropathy, yet these disorders share oxidative stress, mitochondrial dysfunction, lipid dysregulation, and altered neuronal excitability. We investigated whether dietary omega-3 polyunsaturated fatty acids modulate ferroptotic [...] Read more.

Neuropathic pain (NP) arises from diverse conditions, including peripheral nerve injury, spinal cord injury (SCI), and painful diabetic neuropathy, yet these disorders share oxidative stress, mitochondrial dysfunction, lipid dysregulation, and altered neuronal excitability. We investigated whether dietary omega-3 polyunsaturated fatty acids modulate ferroptotic stress-associated pathways, defined as lipid peroxidation susceptibility and impaired antioxidant defense rather than overt ferroptotic cell death. Female Sprague–Dawley rats received either a soy oil control diet (SOD) or fish oil omega-3-enriched diet (FOD) before chronic constriction injury (CCI). Behavioral outcomes were assessed using Hargreaves and CatWalk testing, followed by dorsal root ganglion (DRG) RNA sequencing, RT-PCR, and GPX4 ELISA. Previously generated SCI metabolomics and human diabetic serum metabolomic/lipidomic datasets were re-analyzed for shared pathways. FOD attenuated CCI-induced thermal hypersensitivity and improved gait parameters. DRG transcriptomics showed reduced injury-associated transcriptional disruption, enrichment of selenoamino acid metabolism, nonsense-mediated decay, and ribosomal quality-control pathways, and reduced mitochondrial dysfunction pathway activity. Omega-3 increased Gpx1/Gpx4 expression and GPX4 protein, reduced pain-associated genes including Scn10a, Piezo2, Trpa1, and Oprm1, and aligned with selenoamino acid enrichment in SCI and human datasets. Human lipidomics showed MG/DG/PC/PE pathway remodeling. These findings support ferroptotic stress as a plausible shared downstream mechanism modulated by omega-3 supplementation across NP models. Full article

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

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16 pages, 7810 KB

Open AccessArticle

Synergy of Extremely Low-Frequency Electromagnetic Fields (ELFEFs) and Sex Hormones Against Oxidative Stress in Multiple Sclerosis

by Begoña M. Escribano, Manuel E. Valdelvira, Ana Muñoz-Jurado, Montse Feijóo, Eduardo Agüera-Morales, Javier Caballero-Villarraso, Abel Santamaría and Isaac Túnez

Antioxidants 2026, 15(7), 851; https://doi.org/10.3390/antiox15070851 - 6 Jul 2026

Abstract

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method with neuromodulatory capacity in neurodegenerative diseases such as multiple sclerosis (MS). Its therapeutic value is linked to its activity against oxidative stress by activation of antioxidant defenses. The sex hormones, estrogens (E), progesterone [...] Read more.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method with neuromodulatory capacity in neurodegenerative diseases such as multiple sclerosis (MS). Its therapeutic value is linked to its activity against oxidative stress by activation of antioxidant defenses. The sex hormones, estrogens (E), progesterone (P) and testosterone (T), have demonstrated their power as adjuvants to TMS, improving cortical excitability. The aim of this study was to evaluate the effect of these hormones as adjuvants to extremely low-frequency electromagnetic fields (ELFEFs) in the treatment of experimental autoimmune encephalomyelitis (EAE), the experimental model of MS. The effect of these hormones as replacement therapy was also evaluated in ovariectomized rats treated with ELFEFs. Sixty-five female Dark Agouti rats were divided into 13 groups (5 rats/group), in which biomarkers of oxidative stress and the glutathione redox cycle in non-nervous organs (kidney, liver, heart, intestines and blood) were analyzed. The results show that ELFEFs alone are more effective against oxidative stress. However, P and E were more effective than ELFEFs, both as adjuvants and in hormone replacement therapy, in activating the glutathione system. Therefore, it could be concluded that sex hormones play an important role against MS, enhancing the antioxidant effect of ELFEFs. Full article

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9 pages, 716 KB

Open AccessEditorial

Antioxidants and Aquaculture: A Synergistic Approach for Sustainable Aquatic Production

by Yukun Zhang, Amina Moss and Saichiro Yokoyama

Antioxidants 2026, 15(7), 850; https://doi.org/10.3390/antiox15070850 - 5 Jul 2026

Abstract

Global aquaculture is expanding to meet the increasing demand for high-quality aquatic protein, with projections indicating that the total production of aquatic animals will reach 205 million tonnes by 2032 [...] Full article

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

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37 pages, 3470 KB

Open AccessReview

Ulomoides dermestoides as an Insect Pharmacological Resource of Antioxidant and Anti-Inflammatory Bioactive Substances: Chemical Basis, Mechanisms of Action, Pharmacological Evidence, and Translational Challenges

by Tianzi Wang, Wenling Shi, Xingyue Song, Jinglei Huang, Youqing Cheng, Xiaofan Zhang, Wei Xie and Guoqing Wan

Antioxidants 2026, 15(7), 849; https://doi.org/10.3390/antiox15070849 - 5 Jul 2026

Abstract

Ulomoides dermestoides (Yangchong) is a tenebrionid beetle used in traditional medicine across Asia and Latin America. While crude extracts show effects on inflammation, oxidative stress, and other conditions, systematic integration of its bioactive substances, mechanisms, and translational potential is lacking. This review consolidates [...] Read more.

Ulomoides dermestoides (Yangchong) is a tenebrionid beetle used in traditional medicine across Asia and Latin America. While crude extracts show effects on inflammation, oxidative stress, and other conditions, systematic integration of its bioactive substances, mechanisms, and translational potential is lacking. This review consolidates its chemical basis, comprising volatile benzoquinones, terpenes, and alkenes, alongside non-volatile fatty acids, proteins (antioxidant enzymes, glycoproteins), and phenolics. Pharmacological evidence indicates multi-target modulation of reactive oxygen species (ROS), cytokines, leukocyte recruitment, endothelial activation, and thromboinflammation. Recent advances include proteomic identification of antioxidant protein complexes, neuroprotection in a Parkinson’s disease model, chromosome-level genome assembly, and isolation of the UDP-glucose pyrophosphorylase 2a (UGP2A) glycoprotein, which alleviates thrombosis partly via toll-like receptor 4/myeloid differentiation primary response 88 (TLR4/MyD88)-mediated endothelial anti-inflammatory effects. However, most evidence remains preclinical, relying on non-standardized crude extracts, and benzoquinone-containing fractions display potential cytotoxicity and genotoxicity. Future research should integrate bioassay-guided isolation, structural characterization, multi-omics, pharmacokinetic/pharmacodynamic (PK/PD) analysis, standardized quality markers, and rigorous safety evaluation to transform U. dermestoides from an empirical insect-derived medicinal resource into a scientifically validated source of preclinical antioxidant and anti-inflammatory candidate substances. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Sources with Antioxidant and Anti-Inflammatory Potential)

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20 pages, 17110 KB

Open AccessSystematic Review

Toxicity Evaluation of Nano-Sized Particles by Analysis of mtDNA Content and Expression Levels of Genes Required for mtDNA Maintenance: A Meta-Analysis of Pre-Clinical Studies

by Qiwen Liu, Yunxia Liang, Dongli Xie, Yiming Xu, Dianliang Wang and Xiaogang Luo

Antioxidants 2026, 15(7), 848; https://doi.org/10.3390/antiox15070848 - 4 Jul 2026

Abstract

Mitochondrial alterations, including mitochondrial DNA (mtDNA) loss and defects in maintenance pathways, have been recognized as an important driver for toxic effects of environmental pollutants. Therefore, exposure to nano-sized particles (1–100 nm in diameter; a new source of environmental pollution) may also result [...] Read more.

Mitochondrial alterations, including mitochondrial DNA (mtDNA) loss and defects in maintenance pathways, have been recognized as an important driver for toxic effects of environmental pollutants. Therefore, exposure to nano-sized particles (1–100 nm in diameter; a new source of environmental pollution) may also result in these mitochondrial impairments; however, controversial results have been reported. Available studies collected from three electronic databases through July 2025 were pooled for a comprehensive assessment. Meta-analysis of 19 in vitro studies (69 datasets) showed exposure to nano-sized particles significantly reduced mtDNA content [standardized mean difference = −1.08; p-value = 0.001). The expression levels of mtDNA-encoded (ND1, COX1,2, CYTB, ATP6), mitochondrial biogenesis (SIRT1, PGC-1α, TFAM) and fusion genes (MFN1, MFN2, OPA1) were found to be significantly down-regulated, while fission genes DRP1 and FIS1 were up-regulated following nano-sized particle exposure after meta-analysis of corresponding in vitro and in vivo studies. Accordingly, mtDNA depletion and expression disruption in mtDNA-encoded and maintenance genes may represent important contributors to nano-sized particle exposure-induced diseases. Full article

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27 pages, 6098 KB

Open AccessArticle

Assessing the In Vitro Effects of Carrot Pomace Extract on Intestinal Epithelium Integrity and Functions

by Ana Maria Ciupitu, Gina Cecilia Pistol, Valeria Cristina Bulgaru, Iulian Alexandru Grosu, Alexandra Gabriela Oancea, Norica Branza-Nichita and Ionelia Taranu

Antioxidants 2026, 15(7), 847; https://doi.org/10.3390/antiox15070847 - 4 Jul 2026

Abstract

Carrot processing for juice generates substantial pomace residues rich in bioactive compounds, which represent both an environmental challenge and an unexploited resource. This study investigated the protective effects of a polyphenolic extract derived from carrot pomace (CP) against Escherichia coli lipopolysaccharide (LPS)-induced damage. [...] Read more.

Carrot processing for juice generates substantial pomace residues rich in bioactive compounds, which represent both an environmental challenge and an unexploited resource. This study investigated the protective effects of a polyphenolic extract derived from carrot pomace (CP) against Escherichia coli lipopolysaccharide (LPS)-induced damage. For that, we used IPEC-1 (Intestinal Porcine Epithelial Cells) as an in vitro model of the intestinal epithelium. The total phenolic content of the CP polyphenolic extract (CPE) was 1.017 mg GAE/mL, with flavan-3-ols (epicatechin, catechin, epigallocatechin) accounting for 71.3% of that value. Before being exposed to LPS (10 μg/mL) for 24 h, the cells were pre-treated with CP extract (20.34 µg and 10.17 µg polyphenols/mL of extract corresponding to 1/50 and 1/100 dilution) for 4 h. Epithelial renewal (cell viability, cell proliferation and apoptosis), monolayer/barrier integrity (TEER, FD4 permeability, LDH release), as well as epithelial functionality (synthesis of pro-inflammatory cytokines: TNF-α, IL-1β, IL-6, reactive oxygen species (ROS), nitric oxide (NO) production), MAPK signalling and mitochondrial morphology and function were assessed. The results showed that CP extract had no cytotoxic effects and successfully counteracted LPS-induced loss of cell viability and proliferation. The pre-treatment with CPE at both dilutions significantly reduced LPS-induced apoptosis and cell death. Barrier integrity was preserved with TEER values maintained near baseline: −0.43% and −0.24% for 1/50 and 1/100 dilutions of CPE vs. −53.47% at 72 h for LPS alone, and paracellular FD4 passage was restored to control levels. At the molecular level, CP extract reduced pro-inflammatory cytokine gene expression (IL-6 by 40%, TNF-α by 50–56%) and suppressed LPS-induced MAPK activation by 62.9% and 46.5%, for 1/50 and 1/100 dilutions of CPE, respectively. The pre-treatment of cells with CP extract normalised LPS-induced ROS production and protected mitochondrial morphology and function. These in vitro findings demonstrate that CP extract exerts a protective effect on intestinal epithelial cells, acting through anti-inflammatory, antioxidant and barrier-preserving mechanisms. This supports the hypothesis for valorisation of carrot agro-industrial by-products as functional feed additives for promoting intestinal health. Further in vivo studies are needed to validate this hypothesis and to establish the concentration/rate of inclusion of carrot by-products to achieve the maximal positive effects. Full article

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21 pages, 9362 KB

Open AccessArticle

A Novel Indigoidine-like NRPS Gene from Arthrobacter antioxidans QL17 Enhances Oxidative Stress Resistance Through Radical Scavenging and Transcriptional Reprogramming

by Xue Yu, Yujie Wu, Wei Zhang, Gaosen Zhang, Shiyu Wu, Xiaomin Niu, Liguo Yang, Qi Feng, Tuo Chen and Guangxiu Liu

Antioxidants 2026, 15(7), 846; https://doi.org/10.3390/antiox15070846 - 4 Jul 2026

Abstract

Water-soluble blue microbial pigments with antioxidant activity remain rare, and their host-level protective mechanisms are poorly understood. Here, we identified the genetic basis of blue pigment biosynthesis in the glacier-derived strain Arthrobacter antioxidans QL17. Heavy-ion mutagenesis yielded a hyperpigmented mutant (M157) and a [...] Read more.

Water-soluble blue microbial pigments with antioxidant activity remain rare, and their host-level protective mechanisms are poorly understood. Here, we identified the genetic basis of blue pigment biosynthesis in the glacier-derived strain Arthrobacter antioxidans QL17. Heavy-ion mutagenesis yielded a hyperpigmented mutant (M157) and a pigment-deficient mutant (M186), and pigment yield was positively associated with hydrogen peroxide (H₂O₂) tolerance. Genome mining identified MWM45_RS16760 as the sole core biosynthetic gene in a candidate nonribosomal peptide synthetase (NRPS)-like cluster. The encoded protein displayed an adenylation–peptidyl carrier protein–thioesterase (A-PCP-TE) architecture with a predicted L-glutamine-specific A domain, and its transcript abundance paralleled pigment production across the three strains. Phylogenetic analysis placed MWM45_RS16760 in a distinct actinomycete-associated indigoidine-like lineage separated from the characterized BpsA and IndC branches. Heterologous expression in Escherichia coli reconstructed a blue-pigment-producing phenotype, increased H₂O₂ tolerance, and was accompanied by enhanced extracellular DPPH and ABTS radical-scavenging activities in the culture supernatant. Comparative transcriptomics further revealed coordinated activation of oxidative-stress and proteostasis responses alongside repression of tryptophan biosynthesis and flagellar assembly. These findings identify MWM45_RS16760 as a candidate indigoidine-like NRPS associated with blue pigment biosynthesis and oxidative-stress resistance, with heterologous expression linked to enhanced radical scavenging and coordinated transcriptional reprogramming, expanding the phylogenetic and functional diversity of indigoidine-like systems. Full article

(This article belongs to the Topic Microbial Redox Biology: From Stress Response to Biotechnology)

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