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Antioxidants
Volume 14
Issue 8
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Antioxidants, Volume 14, Issue 8 (August 2025) – 134 articles

Cover Story (view full-size image): Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder with limited therapeutic options and heterogeneous treatment responses. In this study, we investigated the hepatoprotective effects of red ginseng, focusing on the role of saponin fractions in distinct diet-induced MASLD mouse models. Saponin treatment improved steatosis, inflammation, and fibrosis, particularly in the high-fat-diet model, and reduced hepatic iron accumulation. Transcriptomic and molecular analyses identified HAMP1 as a potential exploratory biomarker associated with therapeutic response. These findings were further validated using patient-derived human liver organoids, supporting translational relevance. Our results highlight biomarker-driven stratification as a strategy to optimize red ginseng therapy in MASLD… View this paper
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15 pages, 6299 KB  
Article
Qualitative and Quantitative Metabolite Comparison of Grain, Persimmon, and Apple Vinegars with Antioxidant Activities
by Hyun-Ji Tak, Sowon Yang, So-Young Kim, Na-Rae Lee and Choong Hwan Lee
Antioxidants 2025, 14(8), 1029; https://doi.org/10.3390/antiox14081029 - 21 Aug 2025
Viewed by 643
Abstract
Fermented vinegars have been highlighted globally for their health benefits. The benefits can differ according to the type of vinegar; therefore, we investigated the differences of 15 grain (GV), 10 persimmon (PV), and 14 apple vinegars (AV) using integrated non-targeted and targeted metabolome [...] Read more.
Fermented vinegars have been highlighted globally for their health benefits. The benefits can differ according to the type of vinegar; therefore, we investigated the differences of 15 grain (GV), 10 persimmon (PV), and 14 apple vinegars (AV) using integrated non-targeted and targeted metabolome analyses. We profiled non-volatile and volatile metabolites using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), ultra-high-performance liquid chromatography–orbitrap–tandem mass spectrometry, and headspace–solid-phase microextraction–GC-TOF-MS. Among the 132 identified metabolites, 73 non-volatile and 40 volatile metabolites showed significant differences across the three vinegar types. Amino acids, hydroxy fatty acids, phenolic compounds, aldehydes, pyrazines, and sulfides were abundant in GV. Some phenolic compounds, alcohols, and esters were abundant in PV, whereas carbohydrates, flavonoids, and terpenoids were abundant in AV, contributing to nutrients, tastes, and flavors. Bioactivity assays revealed that GV showed notable antioxidant activity, whereas PV and AV had the highest total phenolic and flavonoid contents, respectively. Through quantitative analysis, we revealed that acetic acid, propionic acid, butanoic acid, lactic acid, and alanine were major components in the three types of vinegar, although their composition was different in each vinegar. Our comprehensive qualitative and quantitative metabolite comparison provides insights into the differences among the three vinegar types, classified according to their raw materials. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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12 pages, 2542 KB  
Article
Cumulative Low-Dose-Rate Radiation Induces Oxidative Stress, Apoptosis, and Fibrosis in Mouse Testis
by Eun-Jin Kim, Anjas Happy Prayoga, Jina Ha, Deok Gyeong Kang, Jinsung Yang, Sohi Kang, Jin-Mok Kim, Byeonggyu Ahn, Dang Long Cao, Seung Pil Yun, Bo Hyun Lee, Joong-Sun Kim and Dawon Kang
Antioxidants 2025, 14(8), 1028; https://doi.org/10.3390/antiox14081028 - 21 Aug 2025
Viewed by 401
Abstract
Ionizing radiation is a well-known environmental stressor capable of generating excessive reactive oxygen species (ROS), leading to oxidative damage in sensitive tissues, including the reproductive system. While oxidative stress is increasingly implicated in male reproductive dysfunction, the long-term effects of low-dose-rate (LDR) radiation [...] Read more.
Ionizing radiation is a well-known environmental stressor capable of generating excessive reactive oxygen species (ROS), leading to oxidative damage in sensitive tissues, including the reproductive system. While oxidative stress is increasingly implicated in male reproductive dysfunction, the long-term effects of low-dose-rate (LDR) radiation on testicular structure and oxidative status remain underexplored. In this study, mice were exposed to continuous LDR radiation (0.39, 1.29, and 3.46 mGy/h) for 21 days to assess testicular histopathology and oxidative status. Although testis weight did not significantly differ among groups, histological analysis revealed basal membrane disruption and reduced spermatogenic cell populations in irradiated groups. Masson’s Trichrome and Sirius Red staining demonstrated dose-dependent collagen deposition, indicating progressive testicular fibrosis. TUNEL assays confirmed increased germ cell apoptosis in the mid- and high-dose-rate groups. ROS levels were significantly elevated only in the highest-dose group, suggesting a threshold-dependent oxidative stress response. These findings indicate that chronic LDR radiation induces testicular damage primarily through apoptosis and fibrosis, with oxidative stress potentially contributing at higher exposure levels. Full article
(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—3rd Edition)
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21 pages, 4747 KB  
Article
Using Integrated Bioinformatics Analysis to Identify Saponin Formosanin C as a Ferroptosis Inducer in Colorectal Cancer with p53 and Oncogenic KRAS
by Hsin-Chih Chen, Ching-Ying Chen, Pao-Yuan Wang, Pin-Yu Su, Shu-Ping Tsai, Chi-Pei Hsu, Hsiao-Sheng Liu, Chi-Ying F. Huang, Wen-Hsing Cheng, Ming-Fen Lee and Chun-Li Su
Antioxidants 2025, 14(8), 1027; https://doi.org/10.3390/antiox14081027 - 21 Aug 2025
Viewed by 361
Abstract
Ferroptosis, a form of cell death, is characterized by lipid peroxidation and is dependent on iron and reactive oxygen species (ROS). Here, through bioinformatics analysis, formosanin C was predicted to be a ferroptosis inducer in colorectal cancer (CRC) by suppressing antioxidation capacity. Indeed, [...] Read more.
Ferroptosis, a form of cell death, is characterized by lipid peroxidation and is dependent on iron and reactive oxygen species (ROS). Here, through bioinformatics analysis, formosanin C was predicted to be a ferroptosis inducer in colorectal cancer (CRC) by suppressing antioxidation capacity. Indeed, formosanin C induced iron accumulation, lipid ROS formation, and ferroptosis in CRC. We found that TP53 and KRAS were the second and third most frequently mutated genes in CRC and were associated with a poor prognosis. Analyses of differentially expressed genes indicated that fatty acid and labile iron levels tended to be higher in CRC than in normal tissues, suggesting the predisposition of CRC cells to ferroptosis. Transcriptomic analyses in CRC patients further identified that wild-type TP53 and mutant KRAS separately favored ferroptosis. Likewise, p53 knockdown rendered HCT 116 cells less sensitive to ferroptosis, and KRAS HT-29 cells were more sensitive to ferroptosis compared with their parental counterparts. Moreover, formosanin C synergistically enhanced chemosensitivity to cisplatin, and this process was mediated by lipid ROS. Overall, our novel gene-expression screening platform allows for the efficient identification of the biological function of novel phytochemicals, and the data suggest that formosanin C is an effective ferroptosis inducer in CRC cells with p53 or oncogenic KRAS. Full article
(This article belongs to the Special Issue Redox Biomarkers in Cancer)
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18 pages, 1824 KB  
Article
Dietary Carnosic Acid Supplementation Improves the Growth Performance, the Antioxidant Status, and Diversity of Intestinal Microbiota in Broilers
by Sheng Zhang, Qin Wang, Jingjing Dong, Guanhuo Li, Kaiyuan Niu, Junhao Pan, Linghan Xia, Yibing Wang and Shouqun Jiang
Antioxidants 2025, 14(8), 1026; https://doi.org/10.3390/antiox14081026 - 21 Aug 2025
Viewed by 410
Abstract
Carnosic acid (CA), a natural phenolic terpenoid compound, is widely distributed in plants such as sage and rosemary, and exhibits a strong antioxidant capacity. The aim of this study was to investigate the effects of different levels of CA on growth performance, antioxidant [...] Read more.
Carnosic acid (CA), a natural phenolic terpenoid compound, is widely distributed in plants such as sage and rosemary, and exhibits a strong antioxidant capacity. The aim of this study was to investigate the effects of different levels of CA on growth performance, antioxidant capacity, and intestinal health of yellow-feathered broilers, and then to determine the optimal dose of CA to promote sustainable broiler production. A total of 384 1-day-old yellow-feathered broilers were randomly allocated into six treatment groups with eight replicates per group and eight birds per replicate pen. The control group (CON) was fed a basal diet and the CA treated groups (CA5, CA10, CA20, CA40, and CA80) were fed diets given different doses of CA (5, 10, 20, 40, and 80 mg/kg), respectively, for 53 days (1~21 d and 22~53 d). The results showed that, in the later stages of the experiment, supplementation with 10, 20, and 40 mg/kg of CA increased (p < 0.05) the final body weight and average daily gain. Morphometric analyses of the jejunum showed that supplementation of CA increased (p < 0.05) the ratio of villus height to crypt depth (V/C). Antioxidant indices revealed that CA significantly reduced MDA levels in plasma, liver, and jejunum, while enhancing activities of GSH-Px, T-SOD, and T-AOC (p < 0.05). Moreover, CA upregulated hepatic Nrf2, HO-1, GSH-Px, and GSR expression via downregulated Keap1. The analysis of intestinal microbiota showed that CA increased (p < 0.05) microbial α diversity (Ace, Chao, and Sobs indices) and increased (p < 0.05) beneficial bacteria, such as Streptococcus, Enterococcus, and Phascolarctobacterium. In conclusion, CA improves growth performance, antioxidant capacity, intestinal health, and gut microbial diversity in broilers. Under the conditions of this experiment, quadratic regressions for different variables showed that the optimal range for supplemental CA in chicken’s diet was 19.11~76.85 mg/kg. Combined with experimental observation and regression analysis, the optimal level of supplementation was 40 mg/kg. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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22 pages, 1704 KB  
Systematic Review
Therapeutic Potential of Apocynin: A Promising Antioxidant Strategy for Acute Kidney Injury
by Jelena Nesovic Ostojic, Sanjin Kovacevic, Silvio R. De Luka, Milan Ivanov, Aleksandra Nenadovic and Andrija Vukovic
Antioxidants 2025, 14(8), 1025; https://doi.org/10.3390/antiox14081025 - 21 Aug 2025
Viewed by 387
Abstract
Acute kidney injury (AKI) is characterized by a sudden rise in serum creatinine levels, a reduction in urine output, or both. Despite its frequent occurrence in clinical settings, AKI remains poorly understood from a pathophysiological standpoint. As a result, management primarily relies on [...] Read more.
Acute kidney injury (AKI) is characterized by a sudden rise in serum creatinine levels, a reduction in urine output, or both. Despite its frequent occurrence in clinical settings, AKI remains poorly understood from a pathophysiological standpoint. As a result, management primarily relies on supportive care rather than targeted treatments. Emerging evidence underscores the pivotal role of oxidative stress in both the initiation and progression of AKI, thereby identifying it as a potential therapeutic target. This review aims to comprehensively examine the pharmacological effects and underlying mechanisms of apocynin (APO) in the context of AKI, with a particular focus on ischemia–reperfusion injury (IRI) and nephrotoxic-induced AKI. Experimental preclinical studies have consistently demonstrated that APO offers protective effects primarily through its inhibition of NADPH oxidase-mediated oxidative stress. In renal IRI and drug-induced nephrotoxicity models, APO has been shown to attenuate oxidative damage, reduce inflammatory responses, and preserve renal structure and function. These results suggest that it may serve as an effective treatment for reducing kidney damage caused by acute ischemia or exposure to nephrotoxic agents. Although the results are encouraging, further investigation is required to establish the optimal dosing strategy and treatment protocol, as well as to confirm the translational relevance of these findings in human clinical settings. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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30 pages, 4541 KB  
Article
Role of Endoplasmic Reticulum Stress-Associated Genes in Septic Neonatal Foals
by Dipak Kumar Sahoo, David Wong, Biswaranjan Paital, Rebecca E. Ruby and Ashish Patel
Antioxidants 2025, 14(8), 1024; https://doi.org/10.3390/antiox14081024 - 21 Aug 2025
Viewed by 828
Abstract
The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, [...] Read more.
The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, such as the endoplasmic reticulum (ER). Endoplasmic reticulum stress disorder affects multiple cellular signaling pathways, including redox balance, inflammation, and apoptosis, and contributes to the pathogenesis of sepsis. The study aimed to elucidate whether OS conditions in sepsis influenced gene expression associated with ER stress. Blood samples were collected from 7 healthy and 21 hospitalized neonatal foals and processed for RNA extraction. RNA sequencing was employed to identify ER stress-responsive genes. Novel findings reported here indicate activation of the ER stress pathway in foals with sepsis. Several genes associated with ER stress, such as clusterin (CLU), BCL2-like 1 (BCL2L1), ubiquitin specific peptidase 14 (USP14), bifunctional apoptosis regulator (BFAR), and optic atrophy 1 (OPA1), were upregulated and positively correlated with sepsis scores and negatively correlated with the combined activities of antioxidant enzymes. In contrast, X-box binding protein 1 (XBP1), homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1), leucine-rich repeat kinase 2 (LRRK2), and selenoprotein S (SELENOS) were negatively correlated with sepsis scores and were downregulated in sepsis and positively correlated with the combined activities of antioxidant enzymes. Furthermore, a positive correlation was observed between cAMP responsive element binding protein 3 like 2 (CREB3L2) and BCL2L1, as well as between the expressions of USP14 and YOD1 deubiquitinase (YOD1) in sepsis. Similarly, the expression levels of XBP1 and Herpud1 demonstrated a positive correlation with each other in sepsis. Additionally, the downregulation of genes with protective function against OS, such as XBP1, HERPUD1, and SELENOS, in septic foals also highlights their significance in mitigating OS in sepsis treatment. The study reported here highlights the potential of ER stress as a promising therapeutic target and prognostic marker in septic foals. Full article
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24 pages, 1972 KB  
Article
Identification, Quantification, and Antioxidant Evaluation of Phenolic Compounds from Colored Opuntia ficus-indica (L.) Roots Using UHPLC-DAD-ESI-MS/MS
by Elias Benramdane, Ahmad Mustafa, Nadia Chougui, Nawal Makhloufi, Abderezak Tamendjari and Cassamo U. Mussagy
Antioxidants 2025, 14(8), 1023; https://doi.org/10.3390/antiox14081023 - 21 Aug 2025
Viewed by 577
Abstract
This study investigates the phenolic composition and antioxidant potential of root extracts from three Opuntia ficus-indica varieties (green, red, and orange) using ultra-high-performance liquid chromatography coupled with diode array detection and electrospray ionization–tandem mass spectrometry (UHPLC-DAD-ESI-MS/MS). Phenolic compounds were extracted with a hydromethanolic [...] Read more.
This study investigates the phenolic composition and antioxidant potential of root extracts from three Opuntia ficus-indica varieties (green, red, and orange) using ultra-high-performance liquid chromatography coupled with diode array detection and electrospray ionization–tandem mass spectrometry (UHPLC-DAD-ESI-MS/MS). Phenolic compounds were extracted with a hydromethanolic solvent and quantified by spectrophotometric assays, while antioxidant activity was assessed through DPPH, ABTS, iron III reduction, hydroxyl radical, and nitric oxide scavenging methods. A total of 26 compounds were identified, including piscidic acid, epicatechin-3-O-gallate, and isovitexin, with several phenolics newly reported for O. ficus-indica roots. The green and red varieties showed the highest phenolic contents (up to 147.82 mg/g extract) and strong antioxidant capacity, particularly in ABTS (IC50 = 29.38 μg/mL) and hydroxyl radical inhibition (>90%). Relative Antioxidant Capacity Index (RACI) analysis confirmed a consistent correlation between phenolic/flavonoid content and antioxidant efficacy. These findings highlight the analytical relevance of UHPLC-DAD-ESI-MS/MS for profiling underutilized plant matrices and support the potential use of O. ficus-indica root extracts as natural sources of bioactive compounds for pharmaceutical and biomedical applications. Full article
(This article belongs to the Special Issue Antioxidant and Antimicrobial Activity of Plant Extracts and Their Pharmacological Applications)
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18 pages, 1785 KB  
Article
Overload of Glucose Metabolism as Initiating Factor in Diabetic Embryopathy and Prevention by Glyoxalase 1 Inducer Dietary Supplement
by Parri Wentzel, Mingzhan Xue, Naila Rabbani, Ulf J. Eriksson and Paul J. Thornalley
Antioxidants 2025, 14(8), 1022; https://doi.org/10.3390/antiox14081022 - 21 Aug 2025
Viewed by 475
Abstract
Hyperglycemia in early-stage embryogenesis is linked to diabetic embryopathy. High-glucose-concentration-induced accumulation of hexokinase-2 (HK2) may initiate metabolic dysfunction that contributes to diabetic embryopathy, including increased formation of methylglyoxal (MG). In this study, we evaluated changes in HK2 protein levels and embryo dysmorphogenesis in [...] Read more.
Hyperglycemia in early-stage embryogenesis is linked to diabetic embryopathy. High-glucose-concentration-induced accumulation of hexokinase-2 (HK2) may initiate metabolic dysfunction that contributes to diabetic embryopathy, including increased formation of methylglyoxal (MG). In this study, we evaluated changes in HK2 protein levels and embryo dysmorphogenesis in an experimental model of diabetic embryopathy. Rat embryos were cultured with high glucose concentrations, and the effects of glyoxalase 1 (Glo1) inducer, trans-resveratrol and hesperetin (tRES + HESP) were evaluated. Rat embryos, on gestational day 9, were cultured for 48 h in low and high glucose concentrations with or without tRES + HESP. Embryo crown–rump length, somite number, malformation score, concentrations of HK2 and Glo1 protein, rates of glucose consumption, and MG formation were assessed. Under low-glucose conditions, embryos exhibited normal morphogenesis. In contrast, high-glucose conditions led to reduced crown–rump length and somite number, and an increased malformation score. The addition of 10 μM tRES + HESP reversed these high glucose-induced changes by 60%, 49%, and 47%, respectively. Embryos cultured in high glucose showed increases in HK2 concentration (42%), glucose consumption (75%), and MG formation (27%), normalized to embryo volume. These elevated HK2 levels were normalized by treatment with 10 μM tRES + HESP. Thus, high-glucose-induced metabolic dysfunction and embryopathy may both be initiated by HK2 accumulation and may be preventable with tRES + HESP treatment. Full article
(This article belongs to the Special Issue Redox Biology of Glyoxalases and Advanced Glycation End Products in Health and Diseases)
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19 pages, 3217 KB  
Article
Highly Soluble Mussel Foot Protein and Its Derivatives Inhibit Inflammation by Targeting NF-κB/PI3K-Akt Signaling and Promoting M2 Macrophage Polarization
by Na Li, Yu Li, Jiren Xu, Jeevithan Elango and Wenhui Wu
Antioxidants 2025, 14(8), 1021; https://doi.org/10.3390/antiox14081021 - 21 Aug 2025
Viewed by 526
Abstract
Chronic inflammation is closely associated with various diseases, underscoring the need for natural, biocompatible anti-inflammatory candidates. For this purpose, mussel foot protein could be an excellent candidate due to its diverse biological activities. Hence, this study systematically evaluates the anti-inflammatory effects of a [...] Read more.
Chronic inflammation is closely associated with various diseases, underscoring the need for natural, biocompatible anti-inflammatory candidates. For this purpose, mussel foot protein could be an excellent candidate due to its diverse biological activities. Hence, this study systematically evaluates the anti-inflammatory effects of a highly soluble mussel foot protein (HMFP) and HMFP-PEG using LPS-stimulated RAW264.7 cells as an in vitro inflammation model. The results reveal that both HMFP and HMFP-PEG markedly reduced intracellular reactive oxygen species (ROS) levels and suppressed the secretion of pro-inflammatory mediators, including IL-1β, TNF-α, and NO, while promoting the production of anti-inflammatory cytokines such as IL-10 and TGF-β. Mechanistically, both agents markedly inhibited the LPS-induced phosphorylation of PI3K, Akt, NF-κB, and IκB, indicating that their anti-inflammatory effects are mediated via suppression of the PI3K/Akt and NF-κB signaling pathways. Furthermore, HMFP and HMFP-PEG downregulated the expression of the inflammatory marker iNOS and markedly upregulated the M2 macrophage marker CD206, suggesting a role in promoting macrophage polarization toward an anti-inflammatory M2 phenotype. Notably, NF-κB signaling was identified as a key mediator in the anti-inflammatory mechanisms of both HMFP and its PEG-modified form. Collectively, these findings demonstrate that HMFP and HMFP-PEG exert significant anti-inflammatory effects through dual inhibition of NF-κB and PI3K/Akt signaling and by promoting M2 macrophage polarization, indicating their potential as promising candidates for the treatment of inflammation-related diseases. Full article
(This article belongs to the Section ROS, RNS and RSS)
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25 pages, 7866 KB  
Article
Sowing Methods and Strigolactones Alleviate Damage to the Photosynthetic System of Rice Seedlings Under Salt Stress by Enhancing Antioxidant Capacity
by Shaobiao Duan, Liming Zhao, Weinan Chen, Qicheng Zhang, Jiangyuan Ya, Wenji Zhong, Qianqian Shang, Jinji Tu, Hongtao Xiang, Jianqin Zhang and Junhua Zhang
Antioxidants 2025, 14(8), 1020; https://doi.org/10.3390/antiox14081020 - 20 Aug 2025
Viewed by 421
Abstract
Seedling cultivation of rice (Oryza sativa L.) is a critical initial step in rice production. This study investigated the effects of sowing methods and strigolactone (GR24) on rice seedlings under salt stress. Results showed that drill-sown seedlings exhibited superior quality under normal [...] Read more.
Seedling cultivation of rice (Oryza sativa L.) is a critical initial step in rice production. This study investigated the effects of sowing methods and strigolactone (GR24) on rice seedlings under salt stress. Results showed that drill-sown seedlings exhibited superior quality under normal conditions compared to broadcast-sown seedlings. Salt stress significantly increased the contents of Cl−, Na+, reactive oxygen species (ROS), and malondialdehyde (MDA), disrupted chloroplast structure and hormonal balance, and reduced gas exchange parameters and chlorophyll fluorescence parameters. Notably, drill-sowing conferred stronger salt tolerance than broadcast-sowing. Exogenous application of GR24 enhanced activities of antioxidant enzymes—including superoxide dismutase (SOD), ascorbate peroxidase (APX), peroxidase (POD), and catalase (CAT)—and elevated non-enzymatic antioxidant contents such as ascorbic acid (ASA), glutathione (GSH), total phenolics, and flavonoids, alongside related enzyme activities. Concurrently, GR24 reduced Na+ and Cl− accumulation, lowered the Na+/K+ ratio, and increased the contents of K+, Ca2+, Mg2+, and hormones. Consequently, GR24 decreased MDA and ROS levels, protected membrane integrity, reduced electrolyte leakage, repaired chloroplast structure, and improved gas exchange and chlorophyll fluorescence parameters. Due to their superior spatial distribution and photosynthetic efficiency, drill-sown seedlings synergized with GR24 to enhance antioxidant capacity under salt stress, enabling more effective scavenging of peroxidative radicals, stabilization of the photosynthetic system, and mitigation of salt-induced growth inhibition. Ultimately, this combination demonstrated greater stress alleviation than broadcast-sown seedlings. Full article
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15 pages, 3468 KB  
Article
Transcriptomic and Proteomic Insights into 6PPD/6PPD-Q Induced Oxidative Stress in Black-Spotted Frogs
by Wenhui Sun, Bingyi Wang, Sihan Zhang, Zhiquan Liu, Yinan Zhang and Hangjun Zhang
Antioxidants 2025, 14(8), 1019; https://doi.org/10.3390/antiox14081019 - 20 Aug 2025
Viewed by 389
Abstract
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its oxidation product 6PPD-quinone (6PPD-Q) can have lethal effects on aquatic organisms, interfering with gene expression and protein content in aquatic animals. In this study, we performed proteomics and transcriptomics analyses on the livers of black-spotted frogs exposed to 6PPD [...] Read more.
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its oxidation product 6PPD-quinone (6PPD-Q) can have lethal effects on aquatic organisms, interfering with gene expression and protein content in aquatic animals. In this study, we performed proteomics and transcriptomics analyses on the livers of black-spotted frogs exposed to 6PPD and 6PPD-Q. The results showed that 6PPD and 6PPD-Q can cause oxidative stress in the liver, significantly reducing catalase (CAT) and glutathione peroxidase (GSH-Px) levels, with 6PPD-Q having a more significant toxic effect. Through transcriptomics and proteomics analysis, this study identified oxidative stress and immune defense pathways. In this study, the liver of the black-spotted frog provided some molecular insights into the toxicity of 6PPD and 6PPD-Q. Nonetheless, additional investigations are required to gain a clearer comprehension of the possible mechanisms that drive how aquatic organisms react to the toxic effects of 6PPD and 6PPD-Q. Full article
(This article belongs to the Special Issue Antioxidant Defenses and Oxidative Stress Management in Aquaculture)
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13 pages, 1225 KB  
Article
Peritoneal Fluid Modulates Redox Balance and RNA Integrity in Mouse Oocytes: Insights into Endometriosis-Related Oxidative Stress
by Joanne Horton, Simon Lane and Ying Cheong
Antioxidants 2025, 14(8), 1018; https://doi.org/10.3390/antiox14081018 - 20 Aug 2025
Viewed by 815
Abstract
Reactive oxygen species (ROS) are vital for oocyte development, yet the redox state of peritoneal fluid may differ between health and disease. This study investigates the effects of peritoneal fluid from women with and without endometriosis on mouse oocytes’ redox status and RNA [...] Read more.
Reactive oxygen species (ROS) are vital for oocyte development, yet the redox state of peritoneal fluid may differ between health and disease. This study investigates the effects of peritoneal fluid from women with and without endometriosis on mouse oocytes’ redox status and RNA oxidation. Peritoneal fluid samples were collected during laparoscopy from women enrolled in an ethically approved case–control study. Stimulated C57BL6 mouse germinal vesicle oocytes were microinjected with RNA transcribed from a Grx1-roGFP2 construct and imaged to assess redox changes. Further oocytes were incubated in standard media, H2O2, or 20% peritoneal fluid, fixed, and immunostained for 8-OHG to evaluate RNA oxidative damage. Oocytes exposed to endometriosis-affected peritoneal fluid showed significantly less redox reduction (mean change 0.07, p < 0.001) compared to fluid from unaffected women (mean change 0.17, p < 0.001), suggesting impaired antioxidant capacity. Those treated with fluid from women without endometriosis showed a more significant reduction (mean ratio change 0.17, p < 0.001). RNA damage was higher in oocytes incubated in fluid from women with infertility compared to pelvic pain (p < 0.001). These findings suggest an altered oxidative environment of peritoneal fluid in endometriosis may contribute to impaired oocyte quality, highlighting a potential mechanism of infertility in affected women. Full article
(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—3rd Edition)
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12 pages, 1547 KB  
Article
Effects of Photodynamic Therapy and Glucocorticosteroids on Salivary Oxidative Stress in Oral Lichen Planus: A Randomized Clinical Trial
by Patryk Wiśniewski, Magdalena Sulewska, Jagoda Tomaszuk, Anna Zalewska, Sara Zięba, Aleksandra Pietruska, Emilia Szymańska, Katarzyna Winnicka, Mateusz Maciejczyk, Małgorzata Żendzian-Piotrowska and Małgorzata Pietruska
Antioxidants 2025, 14(8), 1017; https://doi.org/10.3390/antiox14081017 - 20 Aug 2025
Viewed by 416
Abstract
Objective: This study aimed to assess the impact of photodynamic therapy (PDT) and topical glucocorticosteroids (GKS) on total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) in the saliva of patients with oral lichen planus (OLP). Methods: Ninety patients [...] Read more.
Objective: This study aimed to assess the impact of photodynamic therapy (PDT) and topical glucocorticosteroids (GKS) on total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) in the saliva of patients with oral lichen planus (OLP). Methods: Ninety patients with histopathologically confirmed OLP were randomly assigned to either the PDT group (n = 50) or the GKS group (n = 40). Unstimulated saliva samples were collected before treatment and at 1, 3, and 6 months post-therapy. TOS, TAC, and OSI were determined using colorimetric assays. Results: Both PDT and GKS significantly reduced TOS over the entire observation period. TAC decreased persistently after GKS but remained stable after PDT except for an initial decline. OSI was significantly lower immediately after PDT but did not show sustained differences. Overall, PDT more effectively and durably restored redox balance compared to GKS. Conclusions: Photodynamic therapy demonstrates superior long-term efficacy in modulating oxidative stress markers in saliva, supporting its role as a promising alternative to topical corticosteroids in managing OLP. Clinically, these findings suggest that PDT may offer a non-invasive, recurrence-reducing, and steroid-sparing treatment alternative for OLP, potentially improving long-term patient outcomes and reducing side effects associated with prolonged corticosteroid use. Full article
(This article belongs to the Special Issue Oxidative Stress in Human Diseases—4th Edition)
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12 pages, 1366 KB  
Article
Association Between Melatonin Use and Cataract Risk: A Target Trial Emulation Retrospective Cohort Study
by Cheng-Hsien Hung, Jing-Yang Huang, Yu-Chien Hung, Min-Yen Hsu and James Cheng-Chung Wei
Antioxidants 2025, 14(8), 1016; https://doi.org/10.3390/antiox14081016 - 20 Aug 2025
Viewed by 422
Abstract
Oxidative stress has been shown to play an important role in the development of cataracts. Melatonin is an endogenous hormone that has been proposed to have a protective effect against oxidative stress; however, its association with the risk of cataracts is uncertain. This [...] Read more.
Oxidative stress has been shown to play an important role in the development of cataracts. Melatonin is an endogenous hormone that has been proposed to have a protective effect against oxidative stress; however, its association with the risk of cataracts is uncertain. This target trial emulation study aimed to investigate the relationship between the use of melatonin and the risk of cataracts using TriNetX electronic health records from 2015 to 2023. Adults aged 40 years or older who were diagnosed with a sleep disorder and initiated treatment with either melatonin or a hypnotic benzodiazepine (BZD) were included. Patients receiving hypnotic BZD therapy constituted the active comparator group. Propensity score matching (PSM) was performed to control for covariance. Exposure was defined as the initiation of melatonin or hypnotic BZD therapy. The primary outcomes were the incidence of age-related cataracts and other cataract types, assessed using Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to reduce potential bias. After PSM, 5507 participants were included in each group. Compared with hypnotic BZD users, melatonin users were associated with a significantly lower risk of age-related cataracts (HR, 0.741; 95% CI, 0.681–0.807) and other cataracts (HR, 0.503; 95% CI, 0.433–0.584). These associations remained consistent across all subgroups and sensitivity analyses. In this target trial emulation cohort study, the use of melatonin was associated with a reduced risk of cataracts, suggesting a potential protective effect that warrants further investigation. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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34 pages, 1544 KB  
Review
Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery
by Malwina Lisek, Natalia Bochenska, Julia Tomczak, Julia Duraj and Tomasz Boczek
Antioxidants 2025, 14(8), 1015; https://doi.org/10.3390/antiox14081015 - 19 Aug 2025
Viewed by 600
Abstract
Ischemic brain and retinal injuries trigger complex molecular cascades involving neuroinflammation, oxidative stress, and neuronal death. Among these mechanisms, epigenetic regulation has emerged as a critical modulator of the injury response. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) dynamically control gene expression by [...] Read more.
Ischemic brain and retinal injuries trigger complex molecular cascades involving neuroinflammation, oxidative stress, and neuronal death. Among these mechanisms, epigenetic regulation has emerged as a critical modulator of the injury response. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) dynamically control gene expression by altering chromatin structure. HDACs often promote neuroinflammation and neuronal apoptosis through repression of neuroprotective and anti-inflammatory genes, while HATs generally enhance the transcription of genes involved in cell survival and repair. In ischemia, specific HDAC isoforms (e.g., HDAC1, HDAC2, HDAC3, and HDAC6) have been implicated in microglial activation, glial reactivity, and disruption of immune balance. Conversely, HATs such as CBP/p300 and Tip60 contribute to neuronal resilience and immune regulation. Understanding the dual and context-dependent roles of these epigenetic enzymes offers promising therapeutic avenues. Selective HDAC inhibitors or HAT activators may represent novel strategies to mitigate ischemic damage, support neuroprotection, and facilitate functional recovery. Full article
(This article belongs to the Special Issue Oxidative Stress in Brain Function—2nd Edition)
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12 pages, 843 KB  
Article
Oxidative Stress, High Density Lipoproteins and Hidradenitis Suppurativa: A Prospective Study
by Elisa Molinelli, Camilla Morresi, Maria Luisa Dragonetti, Edoardo De Simoni, Matteo Candelora, Samuele Marasca, Daisy Gambini, Sara Belleggia, Pietro Dragonetti, Giovanni Di Benedetto, Gianna Ferretti, Tiziana Bacchetti and Oriana Simonetti
Antioxidants 2025, 14(8), 1014; https://doi.org/10.3390/antiox14081014 - 19 Aug 2025
Viewed by 462
Abstract
Hidradenitis suppurativa (HS) is a chronic, inflammatory, immune-mediated skin disease associated with several comorbidities and vascular risk factors. Oxidative stress, inflammation, and altered high-density lipoprotein (HDL) functions play key roles in inflammatory skin diseases. However, the relationship between these factors and HS is [...] Read more.
Hidradenitis suppurativa (HS) is a chronic, inflammatory, immune-mediated skin disease associated with several comorbidities and vascular risk factors. Oxidative stress, inflammation, and altered high-density lipoprotein (HDL) functions play key roles in inflammatory skin diseases. However, the relationship between these factors and HS is not fully understood. The aim of this study was to investigate the relationship between HS and oxidative stress, inflammation, and HDL functions, focusing on inflammatory markers and HDL-related antioxidant properties. We evaluated the serum levels of inflammation markers serum amyloid A (SAA) and monocyte chemoattractant protein-1 (MCP-1) in 44 HS patients and 16 healthy controls. Additionally, we assessed the activity of the antioxidant enzyme paraoxonase-1 (PON1) associated with HDL, as well as the HDL redox properties using a cell-free method. HS patients showed significantly higher serum levels of MCP-1 and SAA compared to controls. PON1 activity was considerably lower in HS patients, suggesting impaired antioxidant functions of HDL. These changes in HDL correlated with the severity of HS but occurred without significant alterations in plasma HDL levels. Our findings indicate that inflammation and oxidative stress could contribute to the dysfunction of HDL in HS patients. Identifying dysfunctional HDL could provide valuable insights into the pathogenesis of HS and its associated complications, offering potential targets for new therapeutic strategies. Full article
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26 pages, 900 KB  
Review
The Role of Antioxidants in Male Fertility: A Comprehensive Review of Mechanisms and Clinical Applications
by David Bouhadana, Marie-Hélène Godin Pagé, Debbie Montjean, Marie-Claire Bélanger, Moncef Benkhalifa, Pierre Miron and Francis Petrella
Antioxidants 2025, 14(8), 1013; https://doi.org/10.3390/antiox14081013 - 19 Aug 2025
Viewed by 1608
Abstract
Oxidative stress is a significant factor in male infertility, with increasing evidence evaluating the role of antioxidants in mitigating its detrimental effects on sperm function and quality. This review examines the mechanisms by which reactive oxygen species (ROS) impact male reproductive health. This [...] Read more.
Oxidative stress is a significant factor in male infertility, with increasing evidence evaluating the role of antioxidants in mitigating its detrimental effects on sperm function and quality. This review examines the mechanisms by which reactive oxygen species (ROS) impact male reproductive health. This article synthesizes the different mechanisms at play and highlights key clinical studies published in the literature that contribute to our understanding of antioxidants to treat male infertility. These studies suggest that supplementation with specific antioxidants may improve sperm parameters and increase fertility outcomes, although results vary depending on dosage, duration, and individual health conditions. Despite promising findings, there are inconsistencies across study methodologies and a lack of standardized treatment protocols, which underscore the need for more rigorous clinical trials. Antioxidant supplementation has the potential to serve as a supportive treatment for male infertility, but it should be approached cautiously and appropriately by carefully selecting patients who are deficient in the administered antioxidants. There is a need to better evaluate the long-term impact on reproductive outcomes and determine the optimal supplementation strategies and patient profiles that would benefit most from supplementation regimens. Full article
(This article belongs to the Special Issue Oxidative Stress and Male Reproductive Health)
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16 pages, 2637 KB  
Article
Evaluation of Anthocyanin Profiling, Total Phenolic and Flavonoid Content, and Antioxidant Activity of Korean Rubus Accessions for Functional Food Applications and Breeding
by Juyoung Kim, Jaihyunk Ryu, Seung Hyeon Lee, Jae Hoon Kim, Dong-Gun Kim, Tae Hyun Ha and Sang Hoon Kim
Antioxidants 2025, 14(8), 1012; https://doi.org/10.3390/antiox14081012 - 18 Aug 2025
Viewed by 426
Abstract
The Rubus genus includes numerous berry species known for their rich phytochemical content and antioxidant properties. However, comparative evaluations of wild and cultivated Rubus germplasms in East Asia remain limited. This study aimed to identify superior resources with potential for use in functional [...] Read more.
The Rubus genus includes numerous berry species known for their rich phytochemical content and antioxidant properties. However, comparative evaluations of wild and cultivated Rubus germplasms in East Asia remain limited. This study aimed to identify superior resources with potential for use in functional foods and breeding through integrated phytochemical and antioxidant profiling. Fifteen accessions collected across Korea were assessed for fruit coloration, total phenolic content (TPC), total flavonoid content (TFC), five antioxidant activities (DPPH, ABTS+, superoxide, ferric-reducing activity power, and Fe2+ chelation), and anthocyanin composition by high-performance liquid chromatography‒Mass spectrometry. The TPC ranged from 1.03 to 7.54 mg g−1 of frozen fruit, and TFC ranged from 2.75 to 7.52 mg g−1 of frozen fruit, with significant differences among accessions (p < 0.05). Black-colored fruits such as R. coreanus and R. ursinus varieties exhibited high anthocyanin levels (approximately total 471 and 316 mg g−1 extracts, respectively), with cyanidin-O-hexoside and cyanidin-3-O-glucoside being the dominant pigments. However, the antioxidant performance of these accessions varied. A wild R. crataegifolius (no. 9, resource F) showed the highest TPC and ranked within the top five in multiple antioxidant assays, despite its moderate anthocyanin content. Correlation analysis revealed that TPC and TFC were significantly associated with antioxidant activity (p < 0.05) but not directly with anthocyanin content. These results suggest that antioxidant potential is influenced by a broader spectrum of phenolic compounds, rather than anthocyanins alone. These findings underscore the need to look beyond visual traits and focus on biochemical evidence when selecting elite Rubus accessions. Full article
(This article belongs to the Special Issue Antioxidant Capacity of Natural Products—2nd Edition)
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22 pages, 1038 KB  
Review
Bioactivities Derived from Dry-Cured Ham Peptides: A Review
by Noelia Hernández Correas, Andrea M. Liceaga, Adela Abellán, Beatriz Muñoz-Rosique and Luis Tejada
Antioxidants 2025, 14(8), 1011; https://doi.org/10.3390/antiox14081011 - 18 Aug 2025
Viewed by 445
Abstract
Dry-cured ham is a traditional food in the Mediterranean diet, which, in addition to its sensory qualities, is a natural source of bioactive peptides generated during the curing process through the action of endogenous enzymes on muscle and sarcoplasmic proteins. These low-molecular-weight peptides [...] Read more.
Dry-cured ham is a traditional food in the Mediterranean diet, which, in addition to its sensory qualities, is a natural source of bioactive peptides generated during the curing process through the action of endogenous enzymes on muscle and sarcoplasmic proteins. These low-molecular-weight peptides have attracted growing interest due to their multiple bioactivities, including antihypertensive, antioxidant, antimicrobial, antidiabetic, and anti-inflammatory effects described in vitro, in vivo, and in preliminary human studies. The identification of specific sequences, such as AAPLAP, KPVAAP, and KAAAAP (ACE inhibitors), SNAAC and GKFNV (antioxidants), RHGYM (antimicrobial), and AEEEYPDL and LGVGG (dipeptidyl peptidase-IV and α-glucosidase inhibitors), has been possible thanks to the use of peptidomics techniques, tandem mass spectrometry, and bioinformatics tools that allow their activity to be characterized, their digestive stability to be predicted, and their bioavailability to be evaluated. This review article summarizes current knowledge on the bioactivities of peptides derived from dry-cured ham, advances in their functional characterization, and challenges associated with their application in functional foods and nutraceuticals, with the aim of providing a comprehensive overview of their potential in health promotion and chronic disease prevention. Full article
(This article belongs to the Special Issue Antioxidant Peptides)
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19 pages, 2912 KB  
Article
Antioxidant Nanohybrid Materials Derived via Olive Leaf Extract Incorporation in Layered Double Hydroxide: Preparation, Characterization, and Evaluation for Applications
by Achilleas Kechagias, Areti A. Leontiou, Alexios Vardakas, Panagiotis Stathopoulos, Maria Xenaki, Panagiota Stathopoulou, Charalampos Proestos, Emmanuel P. Giannelis, Nikolaos Chalmpes, Constantinos E. Salmas and Aris E. Giannakas
Antioxidants 2025, 14(8), 1010; https://doi.org/10.3390/antiox14081010 - 18 Aug 2025
Viewed by 1101
Abstract
In this study, an innovative and sustainable strategy for the valorization of olive leaves, an underutilized agro-industrial byproduct, was developed through enzymatic-assisted aqueous extraction to produce a polyphenol-rich olive leaf extract (OLE). The extract contained notable concentrations of hydroxytyrosol (0.53 mg/L), luteolin-7-o-glucoside (0.70 [...] Read more.
In this study, an innovative and sustainable strategy for the valorization of olive leaves, an underutilized agro-industrial byproduct, was developed through enzymatic-assisted aqueous extraction to produce a polyphenol-rich olive leaf extract (OLE). The extract contained notable concentrations of hydroxytyrosol (0.53 mg/L), luteolin-7-o-glucoside (0.70 mg/L), apigenin-4-o-glucoside (0.18 mg/L), and oleuropein (4.24 mg/L). For the first time, this OLE was successfully nanoencapsulated into layered double hydroxides (LDHs) synthesized at Zn2+/Al3+ molar ratios of 1:1, 2:1, and 3:1, resulting in a series of OLE@LDH_Zn/Al_x/1 nanohybrids. Comprehensive structural characterization confirmed the successful intercalation of OLE within the LDH interlayer galleries. Antioxidant activity (via DPPH assay), total polyphenol content (TPC), and antibacterial tests were conducted to evaluate functionality. Among the nanohybrids, OLE@LDH_Zn/Al_1/1 exhibited the highest TPC (606.6 ± 7.0 mg GAE/L), the lowest EC50,DPPH, EC50,ABTS, and EC50,FRAP values (27.88 ± 1.82, 25.70 ± 0.76, and 39.42 ± 2.16 mg/mL), and superior antibacterial performance against E. coli and S. aureus. Moreover, pH-dependent release revealed targeted polyphenol release under acidic conditions (pH = 1), simulating gastric environments. These results highlight LDHs, particularly with a Zn/Al ratio of 1:1, as promising nanocarriers for the stabilization and controlled release of plant-derived polar phenols, with potential applications in nutrition, food preservation, and biomedicine. Full article
(This article belongs to the Special Issue Plants and Plant-Based By-Products as Valuable Sources of Antioxidants: Current Tendencies and Achievements in Their Exploitation)
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17 pages, 1656 KB  
Article
Limited Chemopreventive Effects of Oral Administration of Polyphenol-60 from Green Tea in the MNU-Induced Rat Mammary Tumor Model
by Adrian Florin Gal, Dumitrița Rugină, Daria Antonia Dumitraș, Alexandru-Flaviu Tabaran, Maria-Cătălina Matei-Lațiu and Sanda Maria Andrei
Antioxidants 2025, 14(8), 1009; https://doi.org/10.3390/antiox14081009 - 18 Aug 2025
Viewed by 416
Abstract
Breast cancer remains one of the most prevalent and lethal malignancies in women and female dogs. Nature offers a plethora of nontoxic medicinal compounds that could be an excellent source of antineoplastic molecules for breast cancer prevention. Due to the closeness of human [...] Read more.
Breast cancer remains one of the most prevalent and lethal malignancies in women and female dogs. Nature offers a plethora of nontoxic medicinal compounds that could be an excellent source of antineoplastic molecules for breast cancer prevention. Due to the closeness of human and rat mammary tumors, one of the best models to study breast cancer is in rats. Accordingly, this study investigated the chemoprophylactic potential of polyphenol-60 (PO-60) from green tea on the mammary tumorigenesis model using female Sprague-Dawley rats. Forty 30-day-old female rats were randomly assigned to four groups (n = 10/group): Group 1 received N-methyl-N-nitrosourea (MNU) intraperitoneally (i.p.), Group 2 received MNU i.p. and 0.5% PO-60 in drinking water, Group 3 received saline i.p. and PO-60, and Group 4 received saline i.p. only. Eventually, rats were subjected to necropsy, histopathology, blood biochemical analysis, and assessment of antioxidative status in liver and mammary tissues. The chronic daily ingestion for 298 days of PO-60 in the MNU-induced mammary tumorigenesis model did not interfere with mammary tumor occurrence and evolution. Still, a decline in GPx and SOD levels in the MNU-inoculated animals (G1/G2 vs. G4) was observed. Catalase activity increased in all groups, except for liver from the individuals inoculated with MNU (G1). Full article
(This article belongs to the Special Issue The Use of Antioxidant-Rich Foods and Supplements in Disease Prevention)
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24 pages, 1099 KB  
Review
Mitochondrial Transfer Between Cancer and T Cells: Implications for Immune Evasion
by Soohyun Chun, Jin An and Man S. Kim
Antioxidants 2025, 14(8), 1008; https://doi.org/10.3390/antiox14081008 - 18 Aug 2025
Viewed by 923
Abstract
Intercellular mitochondrial transfer in the tumor microenvironment (TME) is a paradigm-shifting process that redefines cancer–T cell crosstalk. This review explores its dual nature as both a tumor immune evasion strategy and a promising therapeutic avenue. Crucially, oxidative stress acts as a key regulator, [...] Read more.
Intercellular mitochondrial transfer in the tumor microenvironment (TME) is a paradigm-shifting process that redefines cancer–T cell crosstalk. This review explores its dual nature as both a tumor immune evasion strategy and a promising therapeutic avenue. Crucially, oxidative stress acts as a key regulator, inducing tunneling nanotube (TNT) formation to facilitate this organelle exchange. Tumors exploit this by transferring dysfunctional, reactive oxygen species (ROS) generating mitochondria to T cells to induce senescence while simultaneously hijacking healthy mitochondria from T cells to empower their own metabolism. This directional exchange, quantified by computational tools like mitochondrial-enabled reconstruction of cellular interactions (MERCI), is linked to poor clinical outcomes. Transfer occurs via TNTs, extracellular vesicles, and direct contact. Conversely, the therapeutic transfer of healthy mitochondria from sources like mesenchymal stromal cells can revitalize exhausted T cells, improving chimeric antigen receptor T (CAR-T) cell efficacy. Clinical translation is guided by emerging biomarkers, including circulating mitochondrial DNA (mtDNA), mitochondrial haplogroups, and the tumor mitochondrial transfer (TMT) score. Harnessing this biological axis for next-generation immunotherapies requires overcoming challenges in transfer efficiency and standardization to effectively modulate the tumor redox landscape and immune response. Full article
(This article belongs to the Special Issue Implication of Oxidative Stress in Promoting Cellular Senescence and Associated Pathologies—2nd Edition)
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33 pages, 2203 KB  
Review
Cyclodextrin-Based Nanotransporters as a Versatile Tool to Manage Oxidative Stress-Induced Lung Diseases
by Supandeep Singh Hallan, Francesca Ferrara, Maddalena Sguizzato and Rita Cortesi
Antioxidants 2025, 14(8), 1007; https://doi.org/10.3390/antiox14081007 - 17 Aug 2025
Viewed by 876
Abstract
Oxidative stress is one of the key elements in lung-related complications such as cystic fibrosis, acute lung injury, pulmonary hypertension, bronchopulmonary dysplasia, chronic airway diseases, lung cancer, COVID-19, and many others. Antioxidant and anti-inflammatory therapy can be considered as supportive alternatives in their [...] Read more.
Oxidative stress is one of the key elements in lung-related complications such as cystic fibrosis, acute lung injury, pulmonary hypertension, bronchopulmonary dysplasia, chronic airway diseases, lung cancer, COVID-19, and many others. Antioxidant and anti-inflammatory therapy can be considered as supportive alternatives in their management. However, most naturally derived antioxidants face issues with poor aqueous solubility and stability, which hinder their clinical utility. Remarkably, local pulmonary delivery circumvents the severe limitations of oral delivery, including hepatic first-pass metabolism and organ toxicity, and enables a higher drug payload in the lungs. Here, in this review, we present cyclodextrin as a potential drug carrier for pulmonary administration, exploring the possibilities of its surface modification, complexation with other drug transporters, and loading of cannabidiols, siRNA, and antibodies as future trends. However, the lack of a robust physiological model for assessing the efficacy of lung-oriented drug targeting is a significant concern in its path to clinical and commercial success. Full article
(This article belongs to the Special Issue Applications of Antioxidant Nanoparticles, 2nd Edition)
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18 pages, 2387 KB  
Article
Airway Extracellular Copper Concentrations Increase with Age and Are Associated with Oxidative Stress Independent of Disease State: A Case-Control Study Including Patients with Asthma and COPD
by Andreas Frølich, Rosamund E. Dove, Phe Leong-Smith, Mark C. Parkin, Annelie F. Behndig, Anders Blomberg and Ian S. Mudway
Antioxidants 2025, 14(8), 1006; https://doi.org/10.3390/antiox14081006 - 17 Aug 2025
Viewed by 617
Abstract
Chronic obstructive pulmonary disease (COPD) and asthma are characterised by increased oxidative stress in the lungs. The precise contribution of this stress to COPD aetiology remains unclear, partly due to the confounding influence of physiological ageing. Previous reports of increased oxidative stress in [...] Read more.
Chronic obstructive pulmonary disease (COPD) and asthma are characterised by increased oxidative stress in the lungs. The precise contribution of this stress to COPD aetiology remains unclear, partly due to the confounding influence of physiological ageing. Previous reports of increased oxidative stress in bronchoalveolar lavage (BAL) samples from individuals with COPD may at least in part be attributable to the subjects’ age. This study investigated whether increased metal concentrations at the air–lung interface would contribute to oxidative stress in the lungs. We analysed BAL samples from young and old never-smokers, young asthmatic never-smokers, older smokers without COPD and COPD patients (both current and ex-smokers). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify a range of transition metals, including iron, copper, zinc, arsenic and cadmium. BAL concentrations of copper and zinc were significantly lower in young groups compared to the older groups, irrespective of smoking status or disease (p < 0.001 for both). BAL copper was significantly associated with several markers of oxidative stress, all of which were elevated with age: glutathione disulphide (ρ = 0.50, p < 0.001), dehydroascorbate (ρ = 0.67, p < 0.001) and 4-Hydroxynonenal (ρ = 0.43, p < 0.001). These data indicate that age-related increases in respiratory tract copper concentrations contribute to elevated levels of oxidative stress at the air–lung interface independently of respiratory disease. Full article
(This article belongs to the Special Issue Redox Regulation in COPD: Therapeutic Implications of Antioxidants)
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29 pages, 2797 KB  
Review
Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions
by Johannes A. Eble
Antioxidants 2025, 14(8), 1005; https://doi.org/10.3390/antiox14081005 - 16 Aug 2025
Viewed by 599
Abstract
Almost every cell of a multicellular organism is in contact with the extracellular matrix (ECM), which provides the shape and mechanic stability of tissue, organs and the entire body. At the molecular level, cells contact the ECM via integrins. Integrins are transmembrane cell [...] Read more.
Almost every cell of a multicellular organism is in contact with the extracellular matrix (ECM), which provides the shape and mechanic stability of tissue, organs and the entire body. At the molecular level, cells contact the ECM via integrins. Integrins are transmembrane cell adhesion molecules that connect the ECM to the cytoskeleton, which they bind with their extracellular and intracellular domains. Cysteine residues are abundant in both integrin subunits α and β. If pairwise oxidized into disulfide bridges, they stabilize the folding and molecular structure of the integrin. However, despite the oxidative environment of the extracellular space, not all pairs of cysteines in the extracellular integrin domains are permanently engaged in disulfide bridges. Rather, the reversible and temporary linkage of cystine bridges of these cysteine pairs by oxidation or their reductive cleavage can cause major conformational changes within the integrin, thereby changing ligand binding affinity and altering cellular functions such as adhesion and migration. During recent years, several oxidoreductases and thiol isomerases have been characterized which target such allosteric disulfide bridges. This outlines much better, albeit not comprehensively, the role that such thiol switches play in the redox regulation of integrins. The platelet integrin αIIbβ3 is the best examined example so far. Mostly referring to this integrin, this review will provide insights into the thiol switch-based redox regulation of integrins and the known effects of their allosteric disulfide bridges on conformational changes and cell functions, as well as on the machinery of redox-modifying enzymes that contribute to the redox regulation of cell contacts with the ECM. Full article
(This article belongs to the Special Issue Redox Regulation in Inflammation and Disease—3rd Edition)
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30 pages, 7206 KB  
Article
Preventing Cisplatin-Induced Neuropathy and Related Emotional Disorders with the Coadministration of Duloxetine and Hydrogen-Rich Water in Male and Female Mice
by Ignacio Martínez-Martel, Sylmara Esther Negrini-Ferrari and Olga Pol
Antioxidants 2025, 14(8), 1004; https://doi.org/10.3390/antiox14081004 - 16 Aug 2025
Viewed by 392
Abstract
Cisplatin (CIS)-induced peripheral neuropathy and associated comorbidities have a detrimental effect on the lives of cancer patients. Currently, there are no effective therapies to alleviate these symptoms. Duloxetine (DULO) is a recommended treatment, but it is linked with important side effects, thus making [...] Read more.
Cisplatin (CIS)-induced peripheral neuropathy and associated comorbidities have a detrimental effect on the lives of cancer patients. Currently, there are no effective therapies to alleviate these symptoms. Duloxetine (DULO) is a recommended treatment, but it is linked with important side effects, thus making it essential to explore novel approaches. We examined the impact of a prophylactic treatment with a low dose of DULO combined with hydrogen-rich water (HRW) on CIS-injected C57BL/6 male and female mice as a possible therapy for allodynia, muscle and body weight deficits, and emotive syndromes accompanying this type of chemotherapy. The prophylactic treatment with DULO and HRW prevented mechanical allodynia caused by CIS in both sexes and had greater effects than either treatment given individually. The combined treatment also prevented cold allodynia in male mice but only reduced it in females. Moreover, the coadministration of DULO with HRW avoided muscular deficits in both sexes. Furthermore, the body weight reduction induced by CIS in both sexes was not entirely mitigated by the combined therapy. However, all treatments avoided the anxiety- and depressive-like behaviors elicited by CIS. The antiallodynic actions and prevention of muscular deficits produced by the combined treatment might be explained by the inhibition of oxidative stress, inflammatory responses, and plasticity alterations provoked by CIS in the dorsal root ganglia of these subjects. This study proposes, for the first time, the cotreatment of DULO with HRW as an effective therapy for CIS-induced peripheral neuropathy and reveals the influence of sex on these actions. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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27 pages, 3962 KB  
Article
Optimization of Conventional and Ultrasound-Assisted Extraction to Maximize Recovery of Total Phenolic Content and In Vitro Antioxidant Activity from Crataegus almaatensis Leaves
by Zhanar Nabiyeva, Akerke Kulaipbekova, Serena Carpentieri, Yuliya Pronina, Abdyssemat Samadun, Elmira Assembayeva and Giovanna Ferrari
Antioxidants 2025, 14(8), 1003; https://doi.org/10.3390/antiox14081003 - 16 Aug 2025
Viewed by 516
Abstract
Background: Crataegus almaatensis, an endemic hawthorn species from Kazakhstan, is known for its rich content of phenolic compounds and flavonoids with significant pharmacological potential. This study aimed to optimize and compare conventional solid–liquid extraction (SLE) and ultrasound-assisted extraction (UAE) processes for maximizing [...] Read more.
Background: Crataegus almaatensis, an endemic hawthorn species from Kazakhstan, is known for its rich content of phenolic compounds and flavonoids with significant pharmacological potential. This study aimed to optimize and compare conventional solid–liquid extraction (SLE) and ultrasound-assisted extraction (UAE) processes for maximizing the extractability of bioactive compounds from hawthorn leaves powder. Methods: The effects of temperature, extraction time, ethanol concentration, and solid-to-liquid ratio (or ultrasound power in the case of UAE) on total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity (FRAP, DPPH, and ABTS assays) were systematically evaluated. Results: The UAE method yielded higher concentrations of TPC and TFC, with up to 16% improvement in TPC and reduced ethanol usage (40% (v/v)) compared to SLE (75% (v/v)), demonstrating its efficiency and sustainability. Optimal extraction conditions were identified as 70 °C, 75% ethanol, 34 min, and an S/L ratio of 0.05 g/mL for SLE, 70 °C, 40% ethanol, 44 min, and 100 W US power for UAE. High-resolution HPLC-DAD and LC-Q/TOF-MS analyses confirmed the presence of key phenolic acids and flavonoid glycosides, including chlorogenic acid and apigenin-8-C-glucoside-2′-rhamnoside as the most abundant compounds identified. Conclusions: These findings validate UAE as an innovative, eco-friendly method for extracting bioactive compounds from hawthorn leaves and highlight its potential for developing natural antioxidants for pharmaceutical and nutraceutical applications. Full article
(This article belongs to the Special Issue Antioxidants from Food and Food Wastes for Nutraceutical, Pharmaceutical and Cosmetic Fields)
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34 pages, 3045 KB  
Review
Living on the Edge: ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target
by Noah Brandl, Rebecca Seitz, Noah Sendtner, Martina Müller and Karsten Gülow
Antioxidants 2025, 14(8), 1002; https://doi.org/10.3390/antiox14081002 - 16 Aug 2025
Viewed by 813
Abstract
Reactive oxygen species (ROS) act as double-edged swords in cancer biology—facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant [...] Read more.
Reactive oxygen species (ROS) act as double-edged swords in cancer biology—facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant systems such as the glutathione (GSH) and thioredoxin (Trx), and superoxide dismutases (SODs). These systems maintain redox homeostasis and sustain ROS-sensitive signaling pathways including MAPK/ERK, PI3K/Akt/mTOR, NF-κB, STAT3, and HIF-1α. Targeting the antioxidant defense mechanisms of cancer cells has emerged as a promising therapeutic strategy. Inhibiting the glutathione system induces ferroptosis, a non-apoptotic form of cell death driven by lipid peroxidation, with compounds like withaferin A and altretamine showing strong preclinical activity. Disruption of the Trx system by agents such as PX-12 and dimethyl fumarate (DMF) impairs redox-sensitive survival signaling. Trx reductase inhibition by auranofin or mitomycin C further destabilizes redox balance, promoting mitochondrial dysfunction and apoptosis. SOD1 inhibitors, including ATN-224 and disulfiram, selectively enhance oxidative stress in tumor cells and are currently being tested in clinical trials. Mounting preclinical and clinical evidence supports redox modulation as a cancer-selective vulnerability. Pharmacologically tipping the redox balance beyond the threshold of cellular tolerance offers a rational and potentially powerful approach to eliminate malignant cells while sparing healthy tissue, highlighting novel strategies for targeted cancer therapy at the interface of redox biology and oncology. Full article
(This article belongs to the Special Issue Oxidative Stress and Redox Signaling in Cancer Progression and Therapy)
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28 pages, 1659 KB  
Review
The Potential Therapeutic Applications of Natural Products in the Oxidative Stress-Related MVA Pathway: Focus on HMGCR
by Yu-Ning Teng
Antioxidants 2025, 14(8), 1001; https://doi.org/10.3390/antiox14081001 - 16 Aug 2025
Viewed by 599
Abstract
This review explores the therapeutic promise of natural compounds in modulating 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a key enzyme in cholesterol synthesis. HMGCR dysregulation is implicated in dyslipidemia, cardiovascular disease, and cancer, conditions linked to oxidative stress. While statins inhibit HMGCR, their side effects [...] Read more.
This review explores the therapeutic promise of natural compounds in modulating 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a key enzyme in cholesterol synthesis. HMGCR dysregulation is implicated in dyslipidemia, cardiovascular disease, and cancer, conditions linked to oxidative stress. While statins inhibit HMGCR, their side effects necessitate exploring alternatives. The review highlights various natural compounds—flavonoids, phenolic acids, stilbenes, and herbal formulations—with HMGCR-modulating and antioxidant capabilities. In vitro and in vivo studies suggest these compounds offer a promising avenue for treating HMGCR-related conditions. Synergistic effects are observed when combining natural products with statins, hinting at combination therapies that could lower statin dosages and reduce adverse effects. Natural HMGCR modulators hold therapeutic promise but face hurdles like limited in vivo data, regulatory issues, variability in composition, potential drug interactions, and safety concerns. Future research must prioritize comprehensive mechanistic studies, standardized preparations, and well-designed clinical trials. Overcoming these challenges through rigorous science is essential for integrating natural HMGCR modulators into clinical practice and improving patient outcomes in a safe and effective manner. Specifically, clinical trials should consider combination therapies and comparison with standard treatments like statins. More research is also needed on optimal dosages and treatment regimens. Full article
(This article belongs to the Topic Exploring the Cytotoxic and Antioxidant Potential of Plant Extracts)
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Article
Implications of CD36 Gene Variants in Oxidative Stress Markers Between Mexican Patients with Type 2 Diabetes and ST-Segment Elevation Myocardial Infarction
by Brenda Parra-Reyna, Iliannis Yisel Roa-Bruzón, Texali Candelaria García-Garduño, Luis Felix Duany-Almira, Antonio Quintero-Ramos, Jorge Ramón Padilla-Gutiérrez, Héctor Enrique Flores-Salinas, Emmanuel Valdes-Alvarado, José Francisco Muñoz-Valle and Yeminia Valle
Antioxidants 2025, 14(8), 999; https://doi.org/10.3390/antiox14080999 - 15 Aug 2025
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Abstract
Type 2 diabetes mellitus (T2DM) affects 90% of diabetes cases and worsens cardiovascular health by causing oxidative stress, which leads to oxidized LDL (oxLDL) and foam cell formation, contributing to atherosclerosis. This study examined the relationship between CD36 gene variants, soluble CD36 (sCD36), [...] Read more.
Type 2 diabetes mellitus (T2DM) affects 90% of diabetes cases and worsens cardiovascular health by causing oxidative stress, which leads to oxidized LDL (oxLDL) and foam cell formation, contributing to atherosclerosis. This study examined the relationship between CD36 gene variants, soluble CD36 (sCD36), oxLDL, and MDA-LDL in T2DM and ST-segment elevation myocardial infarction (STE-T2DM) patients in western Mexico. The analysis included 400 T2DM patients, 400 STE-T2DM patients, and 400 healthy controls. Results showed that STE-T2DM patients were older, mainly male, and had higher rates of smoking, sedentarism, and hypertension. Both diabetic groups exhibited elevated triacylglycerols and low HDL, with significantly higher C-reactive protein in STE-T2DM (p < 0.0001). No significant differences in CD36 gene variant frequencies were found, but sCD36 levels were elevated in STE-T2DM, with associations to specific genotypes. oxLDL was higher in STE-T2DM compared to controls (p = 0.0268). Binary logistic regression analysis identified male sex, younger age, sedentarism, and rs3173798 T/T genotype as independent risk factors for myocardial infarction (AUC: 0.9267, p < 0.0001). Elevated sCD36 levels may reflect atherosclerosis progression in diabetes, indicating the need for further studies to clarify CD36’s role in cardiometabolic dysfunction. These findings highlight CD36’s involvement in oxidative stress responses through its interaction with oxLDL and MDA-LDL, suggesting its potential role as a molecular target in antioxidant defense mechanisms. Full article
(This article belongs to the Section Aberrant Oxidation of Biomolecules)
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