Antioxidants

28 pages, 6827 KiB

Open AccessArticle

Targeting Spermine Oxidase to Mitigate Traumatic Brain Injury Pathology in the Aging Brain

by Jui-Ming Sun, Jing-Shiun Jan, Ting-Lin Yen, Yu-Hao Chen, Ruei-Dun Teng, Chih-Hao Yang and Cheng-Ta Hsieh

Antioxidants 2025, 14(6), 709; https://doi.org/10.3390/antiox14060709 (registering DOI) - 11 Jun 2025

Abstract

Traumatic brain injury (TBI) in the elderly is frequently associated with worsened neurological outcomes and prolonged recovery, yet the age-specific molecular mechanisms driving this vulnerability remain poorly understood. Aging is characterized by increased oxidative stress and chronic neuro-inflammation, both of which may amplify [...] Read more.

Traumatic brain injury (TBI) in the elderly is frequently associated with worsened neurological outcomes and prolonged recovery, yet the age-specific molecular mechanisms driving this vulnerability remain poorly understood. Aging is characterized by increased oxidative stress and chronic neuro-inflammation, both of which may amplify the brain’s susceptibility to injury. In this study, we identify spermine oxidase (SMOX), a polyamine-catabolizing enzyme that produces reactive oxygen species, as a key mediator linking oxidative stress and neuro-inflammation to age-dependent TBI susceptibility. Using a mouse model of controlled cortical impact (CCI), we found that SMOX expression was significantly upregulated in aged brains, primarily in neurons and microglia, and this increase correlated with greater microglial activation, elevated pro-inflammatory cytokine expression, and widespread neuronal degeneration. Notably, SMOX upregulation also impaired astrocytic glutamate clearance by disrupting the membrane localization of the transporter GLT-1, contributing to excitotoxic stress. Importantly, analysis of postmortem human brain samples and transcriptomic data revealed a parallel age-related increase in SMOX expression, supporting its translational relevance. The pharmacological inhibition of SMOX with JNJ-9350 in aged mice reduced oxidative and inflammatory markers, preserved neuronal viability, and improved motor, cognitive, and emotional outcomes up to 30 days post-injury. These findings establish SMOX as a critical molecular driver of age-related vulnerability to TBI and highlight its inhibition as a promising therapeutic strategy for improving outcomes in elderly TBI patients. Full article

(This article belongs to the Special Issue Free Radicals, Antioxidants, and Oxidative Stress in Aging and Age-Related Diseases—2nd Edition)

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13 pages, 801 KiB

Open AccessCommunication

Impact of Obesity Caused by a High-Fat Diet on the Heart’s Redox Balance

by Yildy Utreras-Mendoza, Isidora Mujica Valenzuela, Luis Montecinos, Paulina Donoso and Gina Sánchez

Antioxidants 2025, 14(6), 708; https://doi.org/10.3390/antiox14060708 (registering DOI) - 11 Jun 2025

Abstract

Obesity has been implicated in the induction of oxidative stress, which is thought to contribute to the pathogenesis of various cardiovascular diseases, including cardiac hypertrophy. However, the redox status during the early stages of cardiac hypertrophy remains inadequately characterized. In this study, we [...] Read more.

Obesity has been implicated in the induction of oxidative stress, which is thought to contribute to the pathogenesis of various cardiovascular diseases, including cardiac hypertrophy. However, the redox status during the early stages of cardiac hypertrophy remains inadequately characterized. In this study, we administered a high-fat diet (HFD) to C57BL/6N mice for 12 weeks. We investigated the expression of biomarkers associated with hypertrophy and oxidative stress, including lipid peroxidation, protein carbonylation, and the redox couples NADH/NAD⁺, NADPH/NADP⁺, and GSH/GSSG. Additionally, we assessed the expression levels and enzymatic activities of catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase. Following 12 weeks on a HFD, mice exhibited obesity and a 10% increase in the heart weight/tibia length ratio, together with an upregulation in the mRNA levels of β-myosin heavy chain, brain natriuretic peptide, and regulator of calcineurin 1, isoform 4. There was also a significant increase in NOX4 content in the heart of these animals; however, we observed no rise in protein carbonylation and a decrease in lipid peroxidation products. As for the redox couples, the GSH/GSSG ratio nearly doubled, while the NADH/NAD⁺ and NADPH/NADP⁺ ratios remained stable. All antioxidant enzyme mRNAs examined showed increased expression; however, only glutathione reductase showed higher activity. Our findings suggest that reductive stress is predominant within the cardiac environment of these animals. Full article

(This article belongs to the Special Issue Antioxidant Research in Chile)

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19 pages, 4005 KiB

Open AccessArticle

Synergistic Effect of TiO₂-Nanoparticles and Plant Growth-Promoting Microorganisms on the Physiological Parameters and Antioxidant Responses of Capsicum annum Cultivars

by Atiya Bhatti, Araceli Sanchez-Martinez, Gildardo Sanchez-Ante, Daniel A. Jacobo-Velázquez, Joaquín Alejandro Qui-Zapata, Soheil S. Mahmoud, Ghulam Mustafa Channa, Luis Marcelo Lozano, Jorge L. Mejía-Méndez, Edgar R. López-Mena and Diego E. Navarro-López

Antioxidants 2025, 14(6), 707; https://doi.org/10.3390/antiox14060707 (registering DOI) - 10 Jun 2025

Abstract

Titanium dioxide nanoparticles (TiO₂-NPs) were synthesized using the molten salt method and systematically characterized. TiO₂-NPs were evaluated for their capacity to promote the growth of Capsicum annuum cultivars together with the plant growth-promoting microorganisms (PGPMs) Bacillus thuringiensis (Bt) and [...] Read more.

Titanium dioxide nanoparticles (TiO₂-NPs) were synthesized using the molten salt method and systematically characterized. TiO₂-NPs were evaluated for their capacity to promote the growth of Capsicum annuum cultivars together with the plant growth-promoting microorganisms (PGPMs) Bacillus thuringiensis (Bt) and Trichoderma harzianum (Th). The variables analyzed included physiological parameters and antioxidant responses. The capacity of TiO₂-NPs to scavenge free radicals was also investigated, along with their biocompatibility, using Artemia salina as an in vivo model. The results demonstrated that TiO₂-NPs exhibited a nanocuboid-type morphology, negative surface charge, and small surface area. It was noted that TiO₂-NPs enhanced the CFU and spore production of Bt (1.56–2.92 × 10⁸ CFU/mL) and Th (2.50–3.90 × 10⁸ spores/mL), respectively. It was observed that TiO₂-NPs could scavenge DPPH, ABTS, and H₂O₂ radicals (IC₅₀ 48.66–109.94 μg/mL), while not compromising the viability of A. salina at 50–300 μg/mL. TiO₂-NPs were determined to enhance the root length and fresh and dry weights of chili peppers. Similarly, TiO₂-NPs in synergy with Bt and Th increased the activity of β-1,3-Glucanase (2.45 nkat/g FW) and peroxidase (69.90 UA/g FW) enzyme activity, and increased the TPC (29.50 GA/g FW). The synergy of TiO₂-NPs with the PGPMs consortium also upregulated the total chlorophyll content: 210.8 ± 11.4 mg/mg FW. The evidence from this study unveils the beneficial application of TiO₂-NPs with Bt and Th as an efficient approach to promote the physiology and antioxidant responses of chili peppers. Full article

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19 pages, 1412 KiB

Open AccessArticle

Renin–Angiotensin System Autoantibody Network in Parkinson’s Disease Patients

by Carmen M. Labandeira, Laura Camacho-Meño, Paula Aracil-Pastor, Juan A. Suárez-Quintanilla, Jose L. Labandeira-García and Ana I. Rodríguez-Pérez

Antioxidants 2025, 14(6), 706; https://doi.org/10.3390/antiox14060706 - 10 Jun 2025

Abstract

The tissue renin–angiotensin system (RAS) is a regulator of oxidative and inflammatory homeostasis by balancing its pro-oxidative/pro-inflammatory axis (angiotensin II, AngII, and AngII type-1 receptor, AT1) and its anti-oxidative/anti-inflammatory axis (AngII/AT2 and ACE2/Ang1-7/Mas receptors). An RAS dysregulation contributes to diseases, including Parkinson’s disease [...] Read more.

The tissue renin–angiotensin system (RAS) is a regulator of oxidative and inflammatory homeostasis by balancing its pro-oxidative/pro-inflammatory axis (angiotensin II, AngII, and AngII type-1 receptor, AT1) and its anti-oxidative/anti-inflammatory axis (AngII/AT2 and ACE2/Ang1-7/Mas receptors). An RAS dysregulation contributes to diseases, including Parkinson’s disease (PD). Immune mechanisms are involved in PD. An increase in levels of pro-oxidative/pro-inflammatory autoantibodies for AT1 (AT1-AAs) and ACE2 (ACE2-AAs) has been recently observed in PD. However, it is not known whether dysregulation of autoantibodies for AT2, MasR, and the correlations among different RAS-AAs occurs in PD. In 106 controls and 117 PD patients, we used enzyme-linked immunosorbent assays to determine correlations among serum RAS-AAs, and among RAS-AAs and pro-inflammatory cytokines and 27-hydroxycholesterol. PD patients showed an increase in MasR-AAs, and a more interconnected cluster of correlations among RAS-AAs (AT1-AA, AT2-AA, MasR-AA, ACE2-AA), changes in RAS-AA networks with sex and age, and differences in networks between RAS-AAs and major PD-related pro-inflammatory cytokines and 27-hydroxycholesterol. The association between AT1-AAs and PD remained significant even after adjustment for age and other variables. This study reveals a disease-specific network of RAS autoantibodies in PD that links immune and oxidative pathways and identifies new biomarker patterns and potential therapeutic targets. Full article

(This article belongs to the Special Issue Oxidative Stress and Neuroinflammation in Neurodegenerative Diseases: Mechanisms and Therapies)

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16 pages, 2414 KiB

Open AccessArticle

Prolonged In Vivo Chemogenetic Generation of Hydrogen Peroxide by Endothelial Cells Induces Cardiac Remodelling and Vascular Dysfunction

by Melina Lopez, Niklas Herrle, Bardia Amirmiran, Pedro F. Malacarne, Julia Werkhäuser, Souradeep Chatterjee, Carine Kader, Victoria Jurisch, Xin Wen, Maedeh Gheisari, Katrin Schäfer, Christian Münch, Florian Leuschner, Ralf Gilsbach, Flávia Rezende and Ralf P. Brandes

Antioxidants 2025, 14(6), 705; https://doi.org/10.3390/antiox14060705 - 10 Jun 2025

Abstract

Increased levels of reactive oxygen species (ROS) are a hallmark of cardiovascular disease. ROS impact the function of proteins largely through thiol modification leading to redox signalling. Acute, targeted interference with local ROS levels has been difficult. Therefore, how dynamics in redox signalling [...] Read more.

Increased levels of reactive oxygen species (ROS) are a hallmark of cardiovascular disease. ROS impact the function of proteins largely through thiol modification leading to redox signalling. Acute, targeted interference with local ROS levels has been difficult. Therefore, how dynamics in redox signalling impact cardiovascular health is still a matter of current research. An inducible, endothelial cell-specific knock-in mouse model expressing a yeast D-amino acid oxidase enzyme was generated (Hipp11-Flox-Stop-Flox-yDAO-Cdh5-CreERT2^+/0 referred to as ecDAO). DAO releases H₂O₂ as a by-product of the conversion of D-amino acids into imino acids. The D-amino acid treatment of DAO-expressing cells therefore increases their intracellular H₂O₂ production. The induction of yDAO in the ecDAO mice was performed with tamoxifen. Subsequently, the mice received D-Alanine (D-Ala, 0.5 M) through drinking water, and the effects on ROS production and vascular and cardiac function were determined. ecDAO induction increased endothelial ROS production as well as ROS production in the lung, which is rich in endothelial cells. The functional consequences of this were, however limited: After minimally invasive myocardial infarction, there was no difference in the outcome between the control (CTL) and ecDAO mice. With respect to vascular function, three days of D-Ala slightly improved vascular function as demonstrated by an increase in the diameter of the carotid artery in vivo and decreased vessel constriction to phenylephrine. Fifty-two days of D-Ala induced cardiac remodelling, increased peripheral resistance, and overoxidation of peroxiredoxins. In conclusion, acute stimulation of endothelial ROS improves cardiovascular function, whereas prolonged ROS exposure deteriorates it. Full article

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

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22 pages, 7381 KiB

Open AccessArticle

Protective Effects of Fish Oil Against Brain Impairment in Rats with Chronic Ethanol-Induced Liver Damage Involving the NRF2 Pathway and Oxidative Stress

by Qian Xiao, Yi-Hsiu Chen, Lu-Chi Fu, Herlin Ajeng Nurrahma, Jing-Huei Lai, Hitoshi Shirakawa and Suh-Ching Yang

Antioxidants 2025, 14(6), 704; https://doi.org/10.3390/antiox14060704 - 10 Jun 2025

Abstract

Fish oil’s neuroprotective effects in ethanol-induced liver injury was investigated through the factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1) pathway. Male Wistar rats received a control liquid diet (C) or an ethanol diet (E), with 25% or 57% of fat replaced by fish [...] Read more.

Fish oil’s neuroprotective effects in ethanol-induced liver injury was investigated through the factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1) pathway. Male Wistar rats received a control liquid diet (C) or an ethanol diet (E), with 25% or 57% of fat replaced by fish oil (CF25, CF57, EF25, EF57) for 8 weeks. Compared to the C group, the E group exhibited brain damage, including impaired performance of Y maze and novel object recognition test, increased glial fibrillary acidic protein (GFAP)-positive astrocytes, and ionized calcium-binding adapter molecule 1 (Iba-1)-positive microglia. In the prefrontal cortex, glutathione (GSH) and phosphorylated (p)-NRF2 decreased, catalase activity increased, and nqo1 mRNA declined; hippocampal NRF2 and nqo1 were also downregulated. However, compared to the E group, the EF25 and EF57 groups exhibited restored spatial and memory functions, reduced GFAP and Iba-1 expressions, potentiated β-amyloid (Aβ) clearance, and escalated catalase activity. Furthermore, increases in p-NRF2 and elevated hippocampal nqo1 mRNA expressions in the prefrontal cortex were observed in the EF25 and EF57 groups. In conclusion, fish oil ameliorated deficits in spatial and memory functions, and enhanced Aβ1-42 clearance in the prefrontal cortex and hippocampus of rats with chronic ethanol-induced liver damage by activating the NRF2/KEAP1 pathway. Full article

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Graphical abstract

18 pages, 3027 KiB

Open AccessArticle

CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile Response

by Jorge Rodríguez-Pérez, Rosa Andreu-Martínez, Leila Pérez-Sánchez, Ana Hernández-García, Cecilia Muñoz-Calleja, Ángel Cogolludo and María J. Calzada

Antioxidants 2025, 14(6), 703; https://doi.org/10.3390/antiox14060703 - 10 Jun 2025

Abstract

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking, is among the most prevalent diseases worldwide. Previous studies have shown that cigarette smoke extract (CSE) can directly affect pulmonary artery function independently of hypoxia resulting from the airway obstruction. In [...] Read more.

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking, is among the most prevalent diseases worldwide. Previous studies have shown that cigarette smoke extract (CSE) can directly affect pulmonary artery function independently of hypoxia resulting from the airway obstruction. In addition, CSE also affects bronchial smooth muscle, leading to airway hyper-responsiveness. However, its specific impact on the contractile machinery of this compartment remains unclear. In this study, using in vitro experiments with human bronchial smooth muscle cells (hBSMCs), we found that CSE exposure disrupted calcium homeostasis, increased ROS and lipid peroxidation, and reduced cell antioxidant defenses. Furthermore, CSE exposure altered the cell contractile apparatus by decreasing key cytoskeletal proteins and impairing actin dynamics, potentially contributing to the dysregulated contractile response of cells. Notably, these effects were significantly attenuated by antioxidant drugs such as mitoTEMPO and N-acetylcysteine, as well as by the inhibition of the endoplasmic reticulum (ER) calcium channels with 2-aminoethoxydiphenyl borate (2-APB). More importantly, mitoTEMPO partially restored the contractile response of bronchus upon CSE challenge. Collectively, our findings give evidence that CSE-mediated increase in ROS and intracellular calcium contribute to cytoskeletal disruption and functional impairment in airway smooth muscle. Moreover, these results also point to potential therapeutical approaches for mitigating the harmful effects of cigarette smoke in the lung. Full article

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

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16 pages, 5107 KiB

Open AccessArticle

Developing a Feeding Module with a Blend of Garlic Oil and Cinnamon Bark for Enhancing Antioxidant Status and Immunity of Murrah Buffalo (Bubalus bubalis) with an Improvement in Feed Efficiency and Reduced Methane Emissions

by Avijit Dey, Shubham Thakur, Ram Kumar Singh, Sandeep Sheoran, Jerome Andonissamy and Sanjay Kumar

Antioxidants 2025, 14(6), 702; https://doi.org/10.3390/antiox14060702 - 10 Jun 2025

Abstract

The experiment was designed to evaluate the consequence of a blend of garlic oil and cinnamon bark powder administration on growth performance, nutrient digestibility, immunity, antioxidant status and methane emission in Murrah buffalo (Bubalus bubalis). Sixteen buffalo calves were divided into [...] Read more.

The experiment was designed to evaluate the consequence of a blend of garlic oil and cinnamon bark powder administration on growth performance, nutrient digestibility, immunity, antioxidant status and methane emission in Murrah buffalo (Bubalus bubalis). Sixteen buffalo calves were divided into two groups in a completely randomised design. The first group (CONT) was fed a basal diet of wheat straw, green oats and concentrate mixture, whereas the second group (GOCB) received feeds as per the CONT along with a blend of garlic oil and cinnamon bark powder (0.5 mL + 1.0 g/head/day) by mixing it with the concentrate mixture for a period of 170 days. The growth rate and feed efficiency in GOCB group buffalo calves were improved (20%) with better (p < 0.05) digestibility of organic matter and crude proteins. Buffaloes of the GOCB group revealed enhanced (p < 0.05) immunity and antioxidant enzymes with reduced (p < 0.05) lipid peroxidation (26% less MDA production). The methane concentration in the eructed gas of the GOCB buffaloes was reduced (33.88%) in comparison with the CONT (p < 0.01). Thus, feed formulated with a blend of garlic oil-cinnamon bark powder demonstrates improvements in the health and production performances of buffalo calves. Full article

(This article belongs to the Special Issue Novel Antioxidants for Animal Nutrition—2nd Edition)

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19 pages, 2360 KiB

Open AccessReview

Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular–Kidney–Metabolic (CKM) Syndrome

by Juan Guerrero-Mauvecin, Natalia Villar-Gómez, Lucia Miño-Izquierdo, Adrián Povo-Retana, Adrian M. Ramos, Gema Ruiz-Hurtado, Maria D. Sanchez-Niño, Alberto Ortiz and Ana B. Sanz

Antioxidants 2025, 14(6), 701; https://doi.org/10.3390/antiox14060701 - 9 Jun 2025

Abstract

The cardiovascular–kidney–metabolic (CKM) syndrome was recently conceptualized to provide a holistic framework for diagnosing and treating the full spectrum of key age-associated interrelated conditions: overweight/obesity, type 2 diabetes mellitus, acute and chronic kidney disease, and cardiovascular disease. This conceptualization resulted from epidemiological associations, [...] Read more.

The cardiovascular–kidney–metabolic (CKM) syndrome was recently conceptualized to provide a holistic framework for diagnosing and treating the full spectrum of key age-associated interrelated conditions: overweight/obesity, type 2 diabetes mellitus, acute and chronic kidney disease, and cardiovascular disease. This conceptualization resulted from epidemiological associations, advances in our understanding of shared and interrelated pathogenic mechanisms, and observations that several drug families improved outcomes in all three components of CKM. Sodium/glucose cotransporter 2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) enhance all CKM spectrum components, although their efficacy varies against specific components. However, the modified mechanisms by these drugs beyond glycemic control in CKM syndrome are poorly understood. We now deeply review the available literature regarding the impact of SGLT2i on oxidative stress and antioxidant defenses in preclinical and clinical studies of type 2 diabetes mellitus, acute and chronic kidney disease, cardiovascular disease, and CKM syndrome. Evidence suggests that SGLT2i may have a secondary antioxidant effect that reduces the vicious cycle of tissue injury—inflammation—tissue injury, even in organs distant from the primary injury. Full article

(This article belongs to the Special Issue Oxidative Stress in Human Diseases—4th Edition)

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21 pages, 6254 KiB

Open AccessArticle

CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling Pathway

by Ning Wang, Jing Leng, Jing Xu, Kelei Qian, Zhiqing Zheng, Gonghua Tao, Ping Xiao and Xinyu Hong

Antioxidants 2025, 14(6), 700; https://doi.org/10.3390/antiox14060700 - 9 Jun 2025

Abstract

Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has been implicated in the pathogenesis of liver diseases. This study investigates the role of circRNA_1156 in neodymium nitrate (Nd(NO₃)₃)-induced hepatocyte ferroptosis. Our in vitro experiments revealed that [...] Read more.

Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has been implicated in the pathogenesis of liver diseases. This study investigates the role of circRNA_1156 in neodymium nitrate (Nd(NO₃)₃)-induced hepatocyte ferroptosis. Our in vitro experiments revealed that exposure to Nd(NO₃)₃ (1.2 µM) significantly reduced the viability of AML12 hepatocytes (p < 0.01), increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) (p < 0.001), and depleted glutathione (GSH) (p < 0.001). However, overexpression of circRNA_1156 effectively reversed these effects and suppressed the expression of ACSL4 and PKCβII (p < 0.01). In our in vivo experiments, chronic exposure to Nd(NO₃)₃ (7–55 mg/kg for 180 days) induced hepatic iron deposition, mitochondrial damage, and activation of the ACSL4/PKCβII pathway (p < 0.01). These adverse effects were significantly ameliorated by circRNA_1156 overexpression (p < 0.05). Our findings identify circRNA_1156 as a novel inhibitor of Nd(NO₃)₃-induced ferroptosis via downregulation of the ACSL4/PKCβII pathway, providing valuable therapeutic insights for hepatotoxicity caused by rare earth element compounds. Full article

(This article belongs to the Special Issue The Janus Face of Oxidative Stress in Normal and Pathological Conditions)

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23 pages, 2126 KiB

Open AccessReview

Current Insight into Biological Markers of Depressive Disorder in Children and Adolescents: A Narrative Review

by Jana Trebatická, Martin Vatrál, Barbora Katrenčíková, Jana Muchová and Zdeňka Ďuračková

Antioxidants 2025, 14(6), 699; https://doi.org/10.3390/antiox14060699 - 9 Jun 2025

Abstract

Depressive disorder (DD) in children and adolescents is a growing public health concern with a complex and multifactorial etiology. While most biomarker research has focused on adults, increasing attention is being paid to age-specific molecular mechanisms. This narrative review provides a comprehensive overview [...] Read more.

Depressive disorder (DD) in children and adolescents is a growing public health concern with a complex and multifactorial etiology. While most biomarker research has focused on adults, increasing attention is being paid to age-specific molecular mechanisms. This narrative review provides a comprehensive overview of current knowledge on potential biomarkers of DD, including genetic, neurotransmitter, hormonal, inflammatory, lipid, and oxidative stress markers, in youth compared to adult populations. Special emphasis is given to findings from the DEPOXIN project (Molecular basis of depressive disorder in children and adolescents, the influence of omega-3 fatty acids and oxidative stress), a multicenter study investigating biological markers in children and adolescents with DD. The project identified significantly increased oxidative stress markers (8-isoprostanes, advanced oxidation protein products, nitrotyrosine) and decreased antioxidant enzyme activity (glutathione peroxidase). Moreover, HDL (high density lipoproteins) cholesterol and its subfractions were negatively correlated with depression severity. At the same time, thromboxane B2, omega-6/omega-3 fatty acid ratios, and salivary cortisol levels showed strong positive correlations with depressive symptoms and biochemical markers of inflammation. These results suggest a distinct molecular profile of depression in paediatric populations, emphasizing the importance of developmental context in biomarker research. The review aims to synthesize existing evidence, compare findings across age groups, and highlight the need for personalized, age-appropriate strategies in the diagnosis and treatment of depressive disorders. Full article

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

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23 pages, 3667 KiB

Open AccessArticle

OTUB1-SLC7A11 Axis Mediates 4-Octyl Itaconate Protection Against Acetaminophen-Induced Ferroptotic Liver Injury

by Ziyun Hu, Yuxin Li, Di Xu, Huihui Meng, Wenya Liu, Qian Xu, Benxing Yao and Junsong Wang

Antioxidants 2025, 14(6), 698; https://doi.org/10.3390/antiox14060698 - 9 Jun 2025

Abstract

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, plays a crucial role in acetaminophen (APAP)-induced hepatotoxicity. While 4-octyl itaconate (4-OI) demonstrates protective effects against APAP toxicity, its molecular mechanisms remain to be fully elucidated. Through an innovative integration of [...] Read more.

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, plays a crucial role in acetaminophen (APAP)-induced hepatotoxicity. While 4-octyl itaconate (4-OI) demonstrates protective effects against APAP toxicity, its molecular mechanisms remain to be fully elucidated. Through an innovative integration of untargeted metabolomics and pathway analysis, we unveil a novel dual mechanism by which 4-OI prevents APAP-induced ferroptosis. We discovered that 4-OI stabilizes SLC7A11 through OTUB1-mediated deubiquitination, thereby restoring cystine import and glutathione (GSH) synthesis. In addition, 4-OI activates the Nrf2 pathway, orchestrating a comprehensive antioxidant response by upregulating the key proteins involved in both glutathione metabolism and iron homeostasis, including GPX4, FTH1, FTL1, and FPN1. This coordinated action effectively prevents the accumulation of toxic iron and lipid peroxides. Our findings not only elucidate the protective mechanisms of 4-OI but also establish it as a promising therapeutic candidate for ferroptosis-related diseases through its unique ability to simultaneously modulate the SLC7A11-GPX4 antioxidant axis and iron homeostasis. Full article

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22 pages, 1107 KiB

Open AccessReview

Oxidative Stress, Gut Bacteria, and Microalgae: A Holistic Approach to Manage Inflammatory Bowel Diseases

by Shani Shoham, Noam Pintel and Dorit Avni

Antioxidants 2025, 14(6), 697; https://doi.org/10.3390/antiox14060697 - 9 Jun 2025

Abstract

Oxidative stress is a recognized contributor to the pathophysiology of inflammatory bowel disease (IBD), exacerbating chronic inflammation and tissue damage. While traditional IBD therapies primarily focus on immune modulation, alternative approaches that address oxidative stress and promote gut microbial health present new opportunities [...] Read more.

Oxidative stress is a recognized contributor to the pathophysiology of inflammatory bowel disease (IBD), exacerbating chronic inflammation and tissue damage. While traditional IBD therapies primarily focus on immune modulation, alternative approaches that address oxidative stress and promote gut microbial health present new opportunities for symptom relief and disease management. Microalgae, known for their potent antioxidant, anti-inflammatory, and prebiotic properties, show promise in alleviating oxidative damage and supporting beneficial gut bacteria. This review explores the multifaceted role of oxidative stress in IBD and highlights the therapeutic potential of microalgae-derived compounds. In addition, it examines the synergistic benefits of combining microalgal antioxidants with probiotics to promote gut homeostasis. Advances in delivery systems, including nanotechnology and symbiotic bacteria–microalgae interactions, are also discussed as emerging approaches for targeted treatment. The review concludes by identifying future research priorities focused on clinical translation and microalgae-based bioengineering innovations to enhance the efficacy and accessibility of therapeutics for IBD patients. Full article

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

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38 pages, 2174 KiB

Open AccessReview

Oxidative Stress: Pathological Driver in Chronic Neurodegenerative Diseases

by Zhao Zhong Chong and Nizar Souayah

Antioxidants 2025, 14(6), 696; https://doi.org/10.3390/antiox14060696 - 9 Jun 2025

Abstract

Oxidative stress has become a common impetus of various diseases, including neurodegenerative diseases. This review introduces the generation of reactive oxygen species (ROSs) in the nervous system, the cellular oxidative damage, and the high sensitivity of the brain to ROSs. The literature review [...] Read more.

Oxidative stress has become a common impetus of various diseases, including neurodegenerative diseases. This review introduces the generation of reactive oxygen species (ROSs) in the nervous system, the cellular oxidative damage, and the high sensitivity of the brain to ROSs. The literature review focuses on the roles of oxidative stress in neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). Oxidative stress occurs when excessively produced free radicals are beyond the capability of endogenous antioxidants to scavenge, leading to the oxidation of proteins, lipids, and nucleic acids, stimulating neuroinflammatory responses, causing neuronal dysfunction, senescence, and death. The dysfunctional mitochondria and aberrant activities of metabolic enzymes are the major source of ROSs. The high vulnerability of the nervous system to ROSs underlies the critical roles of oxidative stress in neurodegenerative diseases. Gene mutations and other risk factors promote the generation of ROSs, which have been considered a crucial force causing the main pathological features of AD, PD, HD, and ALS. As a result, antioxidants hold therapeutic potential in these neurodegenerative diseases. The elucidation of the pathogenic mechanisms of oxidative stress will facilitate the development of antioxidants for the treatment of these diseases. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Neurologic Diseases)

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19 pages, 1240 KiB

Open AccessArticle

Inulin Improves the Redox Response in Rats Fed a Diet Containing Recommended Copper Nanoparticle (CuNPs) Levels, While Pectin or Psyllium in Rats Receive Excessive CuNPs Levels in the Diet

by Aleksandra Marzec, Ewelina Cholewińska, Bartosz Fotschki, Jerzy Juśkiewicz and Katarzyna Ognik

Antioxidants 2025, 14(6), 695; https://doi.org/10.3390/antiox14060695 - 8 Jun 2025

Abstract

The study aimed to determine the effect of dietary inclusion of the recommended (6.5 mg Cu/kg diet) or double the recommended (13.0 mg Cu/kg diet) levels of copper nanoparticles (CuNPs) in combination with different types of dietary fibre on selected redox status indicators [...] Read more.

The study aimed to determine the effect of dietary inclusion of the recommended (6.5 mg Cu/kg diet) or double the recommended (13.0 mg Cu/kg diet) levels of copper nanoparticles (CuNPs) in combination with different types of dietary fibre on selected redox status indicators in the blood and tissues of male Wistar rats. Control groups were fed diets containing cellulose and a mineral mixture with standard or enhanced content of CuCO₃. The experimental groups were fed a diet supplemented with CuNPs (6.5 or 13 mg/kg) and combined with various fibre types—cellulose, pectin, inulin, or psyllium. After the feeding period, rats’ organs were collected to assess selected indicators of redox status. The obtained results suggest that the addition of dietary fibre in the form of inulin may beneficially stimulate the response of the redox system in the conditions of CuNPs nutrition at the recommended dose, pectin, or psyllium in the case of an excessive supply of CuNPs in the diet. Thus, selecting the appropriate type of dietary fibre based on the CuNPs’ level in the diet may effectively protect the organism from the potentially harmful prooxidative effect of CuNPs, ultimately contributing to a favourable regulation of their metabolic impact in the body. Full article

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

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18 pages, 4938 KiB

Open AccessArticle

Isoquercitrin Suppresses Esophageal Squamous Cell Carcinoma (ESCC) by Inducing Excessive Autophagy and Promoting Apoptosis via the AKT/mTOR Signaling Pathway

by Zhibin Liu, Ke Huang, Hai Huang, Eungyung Kim, Hyeonjin Kim, Chae Yeon Kim, Dong Joon Kim, Sang In Lee, Sangsik Kim, Do Yoon Kim, Kangdong Liu, Zae Young Ryoo, Mee-Hyun Lee, Lei Ma and Myoung Ok Kim

Antioxidants 2025, 14(6), 694; https://doi.org/10.3390/antiox14060694 - 8 Jun 2025

Abstract

Esophageal squamous cell carcinoma (ESCC), one of the most frequent malignant tumors of the digestive system, is marked by a poor prognosis and high mortality rate. There is a critical need for effective therapeutic strategies with minimal side effects. Isoquercitrin (IQ) is a [...] Read more.

Esophageal squamous cell carcinoma (ESCC), one of the most frequent malignant tumors of the digestive system, is marked by a poor prognosis and high mortality rate. There is a critical need for effective therapeutic strategies with minimal side effects. Isoquercitrin (IQ) is a natural compound with potent antioxidant properties in cancer and cardiovascular diseases. However, its specific effects and mechanisms in ESCC remain largely unexplored. This study aims to investigate the effects of IQ in ESCC cells and elucidate the mechanisms underlying its therapeutic effects. Specifically, its impact on cell proliferation, colony formation, migration, and invasion was assessed using cell viability assay, morphology, transwell, and colony formation assays. The effects on apoptosis were evaluated by flow cytometry, while immunofluorescence (IF) staining and Western blotting were performed to confirm the underlying mechanisms. The in vivo anti-cancer effects of IQ were then evaluated using a xenograft tumor model. Our results demonstrate that IQ inhibits ESCC cell growth and colony formation while promoting its apoptosis by enhancing caspase activation and downregulating Bcl-2 expression. Furthermore, IQ suppresses cell migration by modulating the epithelial–mesenchymal transition-related proteins. Additionally, IQ induces excessive autophagy by promoting reactive oxygen species accumulation and inhibiting the AKT/mTOR signaling pathway. Importantly, IQ effectively reduces tumor growth in vivo, highlighting its potential as a therapeutic agent for ESCC. Full article

(This article belongs to the Special Issue Redox Signaling in Cancer: Mechanisms and Therapeutic Opportunities)

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28 pages, 7200 KiB

Open AccessArticle

The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H₂S in Drosophila melanogaster

by Victoria Y. Shilova, David G. Garbuz, Lyubov N. Chuvakova, Alexander P. Rezvykh, Sergei Y. Funikov, Artem I. Davletshin, Svetlana Y. Sorokina, Ekaterina A. Nikitina, Olga Gorenskaya, Michael B. Evgen’ev and Olga G. Zatsepina

Antioxidants 2025, 14(6), 693; https://doi.org/10.3390/antiox14060693 - 6 Jun 2025

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Abstract

Here, we describe the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H₂S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of [...] Read more.

Here, we describe the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H₂S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of H₂S production in flies showed minimal levels in the double- and triple-knockout strains. The double- (cbs-/-; cse-/-) and triple- (cbs-/-; cse-/-; dtst-/-) KO flies exhibited a shortened lifespan and reduced fecundity, and showed dramatic changes in Malpighian tubule morphology. The transcriptomic analysis revealed a profound increase in the expression levels of several genes involved in excretory system function in the double-KO and especially the triple-KO flies. Importantly, major groups of differentially expressed genes (DEGs) in the whole bodies of females and ovaries of KO strains included genes responsible for detoxification, reproduction, mitochondrial activity, excretion, cell migration, and muscle system function. The reduced fecundity observed in the double- and triple-KO flies correlated with pronounced changes in the ovarian transcriptome. At the same time, the single knockout of dtst1 increased the flies’ fecundity and lifespan. Our experiments exploring unique Drosophila strains with KO of major H₂S-related genes revealed several new pathways controlled by this ancient adaptogenic system that is involved in various human diseases and aging. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

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23 pages, 6273 KiB

Open AccessArticle

Dynamic Transcriptomic and Cellular Remodeling Underlie Cuprizone-Induced Demyelination and Endogenous Repair in the CNS

by Yantuanjin Ma, Tianyi Liu, Zhipeng Li, Wei Wei, Qiting Zhao and Shufen Wang

Antioxidants 2025, 14(6), 692; https://doi.org/10.3390/antiox14060692 - 6 Jun 2025

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Abstract

Demyelination in the central nervous system (CNS) disrupts neuronal communication and promotes neurodegeneration. Despite the widespread use of cuprizone-induced demyelination models to study myelin injury and repair, the mechanisms underlying oligodendrocyte apoptosis and regeneration are poorly understood. This study investigated the dynamic cellular [...] Read more.

Demyelination in the central nervous system (CNS) disrupts neuronal communication and promotes neurodegeneration. Despite the widespread use of cuprizone-induced demyelination models to study myelin injury and repair, the mechanisms underlying oligodendrocyte apoptosis and regeneration are poorly understood. This study investigated the dynamic cellular and molecular changes that occur during demyelination and remyelination, with a focus on glial cell responses, blood-brain barrier (BBB) integrity, and neuroimmune interactions. C57BL/6J mice exposed to cuprizone exhibited weight loss, sensorimotor deficits, and cognitive decline, which were reversed during remyelination. Histological and immunofluorescence analyses revealed reduced myelin protein levels, including myelin basic protein (MBP) and myelin-associated glycoprotein (MAG), and decreased oligodendrocyte populations during demyelination, with recovery during repair. The BBB permeability increases during demyelination, is associated with the decreased expression of tight junction proteins (ZO-1, Occludin), and normalizes during remyelination. Single-cell RNA sequencing revealed dynamic shifts in glial cell populations and upregulated Psap-Gpr37l1 signaling. Neuroimmune activation and oxidative stress peak during demyelination, characterized by elevated ROS, MDA, and immune cell infiltration, followed by recovery. Transcriptomic profiling revealed key inflammatory pathways (JAK-STAT, NF-κB) and hub genes associated with demyelination and repair. These findings provide insights into myelin repair mechanisms and highlight potential therapeutic targets for treating demyelinating diseases. Full article

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30 pages, 1408 KiB

Open AccessReview

Dynamic Interplay Between Autophagy and Oxidative Stress in Stem Cells: Implications for Regenerative Medicine

by Daniela Rossin, Maria-Giulia Perrelli, Marco Lo Iacono, Raffaella Rastaldo and Claudia Giachino

Antioxidants 2025, 14(6), 691; https://doi.org/10.3390/antiox14060691 - 6 Jun 2025

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Abstract

The crosstalk between autophagy and oxidative stress is a cornerstone of stem cell biology. These processes are tightly interwoven, forming a regulatory network that impacts stem cell survival, self-renewal, and differentiation. Autophagy, a cellular recycling mechanism, ensures the removal of damaged organelles and [...] Read more.

The crosstalk between autophagy and oxidative stress is a cornerstone of stem cell biology. These processes are tightly interwoven, forming a regulatory network that impacts stem cell survival, self-renewal, and differentiation. Autophagy, a cellular recycling mechanism, ensures the removal of damaged organelles and proteins, thereby maintaining cellular integrity and metabolic balance. Oxidative stress, driven by the accumulation of reactive oxygen species (ROS), can act as both a signalling molecule and a source of cellular damage, depending on its levels and context. The interplay between autophagy and oxidative stress shapes stem cell fate by either promoting survival under stress conditions or triggering senescence and apoptosis when dysregulated. Recent evidence underscores the bidirectional relationship between these processes, where autophagy mitigates oxidative damage by degrading ROS-generating organelles, and oxidative stress can induce autophagy as a protective response. This crosstalk is critical not only for preserving stem cell function but also for addressing age-related decline and enhancing regenerative potential. Understanding the molecular mechanisms that govern this interplay offers novel insights into stem cell biology and therapeutic strategies. This review delves into the intricate molecular dynamics of autophagy and oxidative stress in stem cells, emphasizing their synergistic roles in health, disease, and regenerative medicine applications. Full article

(This article belongs to the Special Issue Crosstalk between Autophagy and Oxidative Stress)

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2 pages, 590 KiB

Open AccessCorrection

Correction: Kuo et al. Involvement of HO-1 and Autophagy in the Protective Effect of Magnolol in Hepatic Steatosis-Induced NLRP3 Inflammasome Activation In Vivo and In Vitro. Antioxidants 2020, 9, 924

by Ni-Chun Kuo, Shieh-Yang Huang, Chien-Yi Yang, Hsin-Hsueh Shen and Yen-Mei Lee

Antioxidants 2025, 14(6), 690; https://doi.org/10.3390/antiox14060690 - 5 Jun 2025

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Abstract

In the original publication [...] Full article

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23 pages, 6844 KiB

Open AccessArticle

A Hydrolyzed Soybean Protein Enhances Oxidative Stress Resistance in C. elegans and Modulates Gut–Immune Axis in BALB/c Mice

by Jun Liu, Yansheng Zhao, Fei Leng, Xiang Xiao, Weibo Jiang and Shuntang Guo

Antioxidants 2025, 14(6), 689; https://doi.org/10.3390/antiox14060689 - 5 Jun 2025

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Abstract

Soy protein isolate (SPI) is a high-purity protein from defatted soybeans, providing emulsifying and gelling functions for plant-based foods and supplements. Hydrolysis can facilitate the production of bioactive small-molecule proteins or peptides with potential functional applications. In this study, 20% hydrolyzed soy protein [...] Read more.

Soy protein isolate (SPI) is a high-purity protein from defatted soybeans, providing emulsifying and gelling functions for plant-based foods and supplements. Hydrolysis can facilitate the production of bioactive small-molecule proteins or peptides with potential functional applications. In this study, 20% hydrolyzed soy protein (20% HSP) was prepared from SPI, and the effects of 20% HSP and SPI on alleviating oxidative stress in Caenorhabditis elegans (C. elegans) and regulating immune–gut microbiota in cyclophosphamide (CTX)-induced immunocompromised BALB/c mice were investigated. In C. elegans, both SPI and 20% HSP (300 μg/mL) enhanced locomotive activities, including body bending and head thrashing, and improved oxidative stress resistance under high glucose conditions. This improvement was mediated by increased antioxidant enzyme activities (SOD, CAT, and GSH-Px), while malondialdehyde (MDA) content was reduced by 60.15% and 82.28%, respectively. Both of them can also significantly extend the lifespan of normal C. elegans and paraquat-induced oxidative stress models by inhibiting lipofuscin accumulation. This effect was mediated through upregulation of daf-16 and suppression of daf-2 and akt-1 expression. In immunocompromised mice, 20% HSP alleviated CTX-induced immune dysfunction by increasing peripheral white blood cells and lymphocytes, attenuating thymic atrophy, and reducing hepatic oxidative stress via MDA inhibition. Gut microbiota analysis revealed that 20% HSP restored microbial balance by suppressing Escherichia-Shigella and enriching beneficial genera, like Psychrobacter. These findings highlight 20% HSP and SPI’s conserved anti-aging mechanisms via daf-16 activation in C. elegans and immune–gut modulation in mice, positioning them as plant-derived nutraceuticals targeting oxidative stress and immune dysregulation. Full article

(This article belongs to the Special Issue The Interaction Between Gut Microbiota and Host Oxidative Stress)

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23 pages, 3875 KiB

Open AccessArticle

Chemical Composition, Quality, and Bioactivity of Laurus nobilis L. Hydrosols from the Adriatic Regions of Croatia: Implications for Dermatological Applications

by Lea Juretić, Valerija Dunkić, Ivana Gobin, Suzana Inić, Dario Kremer, Marija Nazlić, Lea Pollak, Silvestar Mežnarić, Ana Barbarić and Renata Jurišić Grubešić

Antioxidants 2025, 14(6), 688; https://doi.org/10.3390/antiox14060688 - 5 Jun 2025

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Abstract

Laurus nobilis L., Lauraceae, bay laurel, has been traditionally used for its various therapeutic properties, and in recent years has been gaining interest for its potential applications in skincare products. However, the biological effects of bay laurel, particularly its hydrosols, a water fraction [...] Read more.

Laurus nobilis L., Lauraceae, bay laurel, has been traditionally used for its various therapeutic properties, and in recent years has been gaining interest for its potential applications in skincare products. However, the biological effects of bay laurel, particularly its hydrosols, a water fraction obtained during essential oil production, remain unexplored. The objective of this study was to identify the volatile compounds in L. nobilis hydrosols (LnHYs) from different coastal regions of Croatia (north, middle, and south Adriatic) and to evaluate their potential safety and efficacy for dermatological applications. Upon isolating LnHYs using microwave-assisted extraction, LnHY volatiles were identified and quantified using gas chromatography and mass spectrometry. Oxygenated monoterpenes were the dominant compounds in all LnHYs (61.72–97.00%), with 1,8-cineole being the most abundant component (52.25–81.89%). The physical and chemical parameters of LnHYs were investigated to assess their purity and quality. Biological activity (cytotoxicity and wound-healing effect) was tested on the human keratinocyte cell line (HaCaT), selected as the experimental model due to its relevance to skin biology. Additionally, contents of polyphenolic substances, antioxidative effects using the Oxygen Radical Absorbance Capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods, and the antimicrobial activity of LnHYs toward five skin microorganisms were determined. All tested hydrosols showed similar biological activity, with only minor differences. Cytotoxicity studies indicated the safety of the dermatological application of LnHYs, and the results of the wound-healing assay showed their neutral to mildly positive effect. Considering the growing use of bay laurel preparations in pharmaceutical and cosmetic applications, extensive studies on their biological activity, quality, and safety are essential to either support or regulate their use in humans. Full article

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2 pages, 445 KiB

Open AccessCorrection

Correction: Longhitano et al. The Crosstalk between GPR81/IGFBP6 Promotes Breast Cancer Progression by Modulating Lactate Metabolism and Oxidative Stress. Antioxidants 2022, 11, 275

by Lucia Longhitano, Stefano Forte, Laura Orlando, Stephanie Grasso, Alessandro Barbato, Nunzio Vicario, Rosalba Parenti, Paolo Fontana, Angela M. Amorini, Giuseppe Lazzarino, Giovanni Li Volti, Michelino Di Rosa, Arcangelo Liso, Barbara Tavazzi, Giacomo Lazzarino and Daniele Tibullo

Antioxidants 2025, 14(6), 687; https://doi.org/10.3390/antiox14060687 - 5 Jun 2025

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Abstract

In the original publication, there was a mistake in Figure 4C as published [...] Full article

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

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19 pages, 5284 KiB

Open AccessArticle

Phosphorus Supplementation Enhances Growth and Antioxidant Defense Against Cadmium Stress in Cotton

by Asif Iqbal, Huiping Gui, Cangsong Zheng, Xiangru Wang, Xiling Zhang, Meizhen Song and Xiaoyan Ma

Antioxidants 2025, 14(6), 686; https://doi.org/10.3390/antiox14060686 - 5 Jun 2025

Viewed by 240

Abstract

Cadmium (Cd) contamination in agricultural soils is increasing due to anthropogenic activities, posing a significant threat to plant growth and productivity. Phosphorus (P) has been suggested as a potential mitigator of Cd toxicity, yet the role of cotton genotypes with contrasting low-P tolerance [...] Read more.

Cadmium (Cd) contamination in agricultural soils is increasing due to anthropogenic activities, posing a significant threat to plant growth and productivity. Phosphorus (P) has been suggested as a potential mitigator of Cd toxicity, yet the role of cotton genotypes with contrasting low-P tolerance in contaminated soils remains largely unexplored. A hydroponic experiment was conducted to assess the effects of Cd stress (5 μM) on Jimian169 (strong-low-P tolerant) and DES926 (weak-low-P tolerant) cotton genotypes under low-P (0.01 mM KH₂PO₄) and normal P (1 mM KH₂PO₄) conditions. The results revealed that Cd stress, especially under low-P, significantly reduced plant growth, dry matter, photosynthetic rate, and P use efficiency (PUE), while increasing oxidative damage through increased malonaldehyde levels and reactive oxygen species accumulation. These adverse impacts were very much evident in DES926 compared to Jimian169. In contrast, Jimian169 demonstrated greater resilience to Cd stress by mitigating oxidative damage through enhanced antioxidant enzyme activity, improved photosynthetic performance, and increased accumulation of osmoprotectants. These findings indicate that Jimian169 can better withstand Cd toxicity by enhancing photosynthesis, antioxidant defense mechanisms, and osmotic adjustment. This makes them a promising candidate for cultivation in Cd-contaminated, P-deficient soils. Full article

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

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21 pages, 1000 KiB

Open AccessArticle

Selenium and Coenzyme Q₁₀ Supplementation and Sex Differences in Cardiovascular Mortality Results from a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly People Low in Selenium

by Urban Alehagen, Jan Olav Aaseth, Lutz Schomburg, Trine B. Opstad, Anders Larsson and Jan Alexander

Antioxidants 2025, 14(6), 685; https://doi.org/10.3390/antiox14060685 - 5 Jun 2025

Viewed by 303

Abstract

Background: Low selenium intake and age-related decline of coenzyme Q₁₀ (CoQ₁₀) have been associated with an increased risk of cardiovascular disease (CVD) and oxidative stress. In a randomised placebo-controlled trial (RTC) in elderly people with low selenium levels, the supplementation [...] Read more.

Background: Low selenium intake and age-related decline of coenzyme Q₁₀ (CoQ₁₀) have been associated with an increased risk of cardiovascular disease (CVD) and oxidative stress. In a randomised placebo-controlled trial (RTC) in elderly people with low selenium levels, the supplementation with selenium and CoQ₁₀ reduced CVD and mortality. However, whether the supplementation elicited sex-specific benefits remained to be explored. Methods: Elderly Swedish persons (n = 443; balanced sex ratio) receiving selenium yeast (200 µg/day) and CoQ₁₀ (200 mg/day) combined or a placebo for four years were followed for additional six years. The response to supplementation, cardiovascular (CV) mortality, and risk factors were determined at four and ten years. Kaplan–Meier analyses, ANCOVA, repeated measurements of variance, and Cox proportional hazard regression analyses were performed. Results: The measured 10-year CV mortality rate was lower in females, and supplementation reduced this risk to a greater extent compared to in males. The improved survival rate apparently kicked in later in females than in males. At baseline, males had a higher smoking rate, increased inflammation and oxidative stress, and a higher prevalence of more advanced ischaemic heart disease (IHD) and signs of heart failure. When stratified by sex, in individuals with IHD, the intervention improved CV survival in both sexes, whereas supplementation had a more pronounced effect in females without IHD at inclusion. Supplementation diminished inflammation and oxidative stress, impaired the increase of NT-proBNP, and improved renal function in both sexes. Conclusions: The supplementation improved CV survival, especially in women. The higher prevalence of structural CVD and smoking in males may have contributed to the observed greater supplementation benefits in females. The preventive impact of selenium and CoQ₁₀ supplementation in elderly males and females may be particularly strong and meaningful in the early stages of CVD development. Full article

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

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14 pages, 1129 KiB

Open AccessArticle

Culture Medium Enriched with Ultrafine Carbon Monoxide Bubbles Enhances In Vitro Blastocyst Formation of In Vivo-Fertilized Mouse Zygotes

by Toyofumi Hirakawa, Kazuhiko Nakabayashi, Noriko Ito, Keisuke Ishiwata, Daichi Urushiyama, Kohei Miyata, Tsukasa Baba, Kenichiro Hata, Shin’ichiro Yasunaga, Fusanori Yotsumoto, Katsuro Tachibana and Shingo Miyamoto

Antioxidants 2025, 14(6), 684; https://doi.org/10.3390/antiox14060684 - 4 Jun 2025

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Abstract

Oxidative stress induced by in vitro culture conditions impedes the differentiation of fertilized zygotes. Gasotransmitters containing carbon monoxide (CO) exhibit antioxidant properties when exogenously administered at appropriate concentrations. In this study, CO was incorporated into ultrafine bubbles (UFBs) to devise an innovative method [...] Read more.

Oxidative stress induced by in vitro culture conditions impedes the differentiation of fertilized zygotes. Gasotransmitters containing carbon monoxide (CO) exhibit antioxidant properties when exogenously administered at appropriate concentrations. In this study, CO was incorporated into ultrafine bubbles (UFBs) to devise an innovative method for promoting the efficient differentiation of fertilized mouse zygotes into blastocysts within an in vitro culture environment. While CO typically dissipates rapidly in culture media, its encapsulation into UFBs enabled its prolonged retention within the medium. Fertilized mouse zygotes cultured in the UFB medium exhibited a significantly higher rate of blastocyst hatching compared to those cultured in conventional media. Furthermore, Gene Ontology analysis revealed elevated expression of mitochondrial-related genes and genes essential for blastocyst maturation in the UFB culture medium. These findings underscore the potential of CO-UFB as a potent agent for improving in vitro blastocyst formation and hatching by mitigating oxidative stress, thereby offering a promising strategy for enhancing assisted reproductive technologies. Full article

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27 pages, 2941 KiB

Open AccessArticle

Multivariate Evaluation of Biofunctional Metabolites in Korean Soybean Cultivars by Use Categories: Assessment of Antioxidant and Enzyme Inhibition Activities

by Kye Man Cho, Se Hyeon Jeon, Eun Jeong Ko, Dong Hyun Park, Ye Ri Jeong, Du Yong Cho, Jeong Ho Kim and Jin Hwan Lee

Antioxidants 2025, 14(6), 683; https://doi.org/10.3390/antiox14060683 - 4 Jun 2025

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Abstract

This research investigates the metabolite composition and biofunctional activiteies of 41 Korean soybeans, categorized by application: bean sprout, bean paste, vegetable, and cooked-with-rice. Isoflavones were identified via UPLC-Q-TOF-MS/MS and quantified using HPLC, revealing malonylgenistin as the predominant composition (average 743.4 μg/g, 42.3% of [...] Read more.

This research investigates the metabolite composition and biofunctional activiteies of 41 Korean soybeans, categorized by application: bean sprout, bean paste, vegetable, and cooked-with-rice. Isoflavones were identified via UPLC-Q-TOF-MS/MS and quantified using HPLC, revealing malonylgenistin as the predominant composition (average 743.4 μg/g, 42.3% of total isoflavones). Bean sprout showed the highest average isoflavone (2780.6 μg/g), followed by bean paste (1837.8 μg/g), cooked-with-rice (1448.2 μg/g), and vegetable (883.2 μg/g), with significant differences in individual cultivars. Protein ranged from 36.8 to 46.6% and oil from 17.0 to 22.3%, with vegetable soybeans exhibiting the highest average protein (44.9%) and lowest average oil (18.6%). Moreover, PLS-DA and hierarchical clustering revealed distinct metabolic patterns in usage groups. Antioxidant activities (radical scavenging; DNA protection) and enzyme inhibition (tyrosinase; α-glucosidase) also varied significantly, correlating with isoflavone distributions. Particularly, Sorog exhibited the highest isoflavone (3722.7 μg/g) and strong antioxidant activity (DPPH: 72.2%; ABTS: 93.8%, 500 μg/mL), DNA protection (92.8%, 200 μg/mL), and inhibition of tyrosinase and α-glucosidase by 78.4% and 84.2% (500 μg/mL). These findings suggest that isoflavone-rich bean sprout soybeans, especially Sorog, are promising candidates for health-promoting foods and functional cultivar development. This is the first systematic study comparing the metabolites and health-related properties of soybeans based on Korean usage categories. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Natural Products—2nd Edition)

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15 pages, 996 KiB

Open AccessReview

The Impact of the Skin Microbiome and Oxidative Stress on the Initiation and Development of Cutaneous Chronic Wounds

by Manuela Martins-Green, Jane Kim and Klara Aziz

Antioxidants 2025, 14(6), 682; https://doi.org/10.3390/antiox14060682 - 4 Jun 2025

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Abstract

Wound healing is a very complex process composed of several phases in which precise events occur, both temporally and specially. However, when these processes go awry, biofilm-forming bacteria become installed in the healing tissue, and the patient has comorbidities, so the wounds do [...] Read more.

Wound healing is a very complex process composed of several phases in which precise events occur, both temporally and specially. However, when these processes go awry, biofilm-forming bacteria become installed in the healing tissue, and the patient has comorbidities, so the wounds do not heal and become chronic. In this review, we describe the importance of high levels of oxidative stress (OS) and bacteria from the skin microbiome in the initiation and development of chronic wounds. The skin microbiome is diverse in humans, and its composition is dependent on the environment in the specific areas of the body. OS is critical for wound healing as it stimulates the immune system to destroy pathogens and secrete cytokines and growth factors that stimulate healing. When OS levels become high in the wound and the bacteria of the skin install themselves in the wound, chronicity ensues. However, neither OS nor the bacteria of the skin alone can initiate chronicity. However, when present together, chronic wounds develop. Given the complexity of chronic wound initiation, developing treatment for these wounds has been difficult. Here, we also discuss the challenges of treating chronic wounds and offer a potential sequence of approaches to treating these wounds after debridement. Full article

(This article belongs to the Special Issue Antioxidant Delivery Strategies for Prevention and Treatment of Skin Pathologies)

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29 pages, 9043 KiB

Open AccessArticle

Arginine-Mediated Liver Immune Regulation and Antioxidant Defense in Largemouth Bass (Micropterus salmoides): Multi-Omics Insights into Metabolic Remodeling During Nocardia seriolae Infection

by Yu-Long Sun, Shuai-Liang Zhang, Feng-Feng Zhou, Yuan-Xin Qian, Yang He, Run-Zhe Zhang, Fen Dong, Qiang Chen, Han-Ying Xu, Ji-Teng Wang, Yu-Ting Deng and Tao Han

Antioxidants 2025, 14(6), 681; https://doi.org/10.3390/antiox14060681 - 3 Jun 2025

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Abstract

The liver of fish is an essential metabolic organ that also serves an immune regulatory role. In this study, we constructed a model of largemouth bass (Micropterus salmoides) infected with Nocardia seriolae by injection to explore the immune and antioxidant functions [...] Read more.

The liver of fish is an essential metabolic organ that also serves an immune regulatory role. In this study, we constructed a model of largemouth bass (Micropterus salmoides) infected with Nocardia seriolae by injection to explore the immune and antioxidant functions of the liver. The results showed that N. seriolae infection caused severe pathological changes in the liver, including cell necrosis, granuloma formation, and leukocyte infiltration. The level of mRNA expression of immune-related genes in the liver was significantly increased 2 days post-infection. Moreover, the combined analysis of transcriptome and metabolome showed that N. seriolae infection markedly affected liver metabolism, including glutathione metabolism, arginine and proline metabolism, arachidonic acid metabolism, as well as starch and sucrose metabolism. Additionally, multiple key biomarkers were identified as involved in regulating responses to N. seriolae infection, including arginine, glutathione, gpx, GST, PLA2G, GAA, and PYG. To further elucidate the regulatory effects of arginine on the immune and antioxidant processes in the liver, primary hepatocytes were isolated and cultured. The results demonstrated that arginine supplementation significantly reduced the expression of LPS-induced apoptosis-related genes (bax, cas3, cas8, and cas9) by up to 50% while increasing the expression of antioxidant genes (gpx, GST) by up to 700% at 24 h. Through the analysis of metabolic changes and immune responses in the liver following N. seriolae infection, combined with in-vitro experiments, this study elucidated the anti-apoptotic and antioxidant effects of arginine, revealing the immune response mechanisms in fish liver and laying the groundwork for using nutritional strategies to improve fish health. Full article

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

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19 pages, 2137 KiB

Open AccessArticle

Optimization of Ultrasound-Assisted Extraction of Phenolic Compounds from Romanian Blackthorn (Prunus spinosa L.) Fruits

by Ana-Maria Drăghici-Popa, Oana Cristina Pârvulescu, Raluca Stan and Ana-Maria Brezoiu

Antioxidants 2025, 14(6), 680; https://doi.org/10.3390/antiox14060680 - 3 Jun 2025

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Abstract

Selecting factors that significantly affect the extraction process and optimizing them are essential to obtain high extraction efficiency. This study aimed at optimizing the ultrasonic-assisted extraction (UAE) of polyphenols from Romanian blackthorn fruits using aqueous solutions of ethanol as green extraction solvents. Six [...] Read more.

Selecting factors that significantly affect the extraction process and optimizing them are essential to obtain high extraction efficiency. This study aimed at optimizing the ultrasonic-assisted extraction (UAE) of polyphenols from Romanian blackthorn fruits using aqueous solutions of ethanol as green extraction solvents. Six process factors, including solvent/plant material ratio (R_LS = 4.95–15.1 cm³/g), ethanol concentration in the extraction solvent (c_et = 16.4–83.6%), extraction temperature (t = 30–70 °C), pH of the solvent (pH = 2–7), amplitude of the ultrasonic probe (A = 30–70%), and extraction time (τ = 5–15 min), were screened and optimized based on a Plackett–Burman design (PBD) and a central composite design (CCD). Statistical analysis indicated that R_LS, c_et, and t significantly affected the process response variables in terms of total phenolic content (TPC), total anthocyanins content (TAC), and antioxidant capacity (AC). Under optimal conditions (R_LS_,opt = 15.1 cm³/g, c_et_,opt = 33.2%, t_opt = 66.8 °C, pH_opt = 7, A_opt = 50%, and τ_opt = 10 min), the following levels of response variables were experimentally determined: TPC_opt = 14.45 ± 0.718 mg GAE/g DM, TAC_opt = 0.405 ± 0.057 mg C3GE/g DM, and AC_opt = 16.75 ± 1.144 mg TE/g DM. Six phenolic compounds were identified in the extract obtained at optimal levels of process factors, i.e., rutin (7.12 ± 0.06 mg/100 g DM), protocatechuic acid (6.83 ± 0.01 mg/100 g DM), neochlorogenic acid (4.88 ± 0.01 mg/100 g DM), vanillic acid (3.70 ± 0.01 mg/100 g DM), chlorogenic acid (1.93 ± 0.02 mg/100 g DM), and caffeic acid (1.51 ± 0.01 mg/100 g DM). Full article

(This article belongs to the Special Issue Green Extraction of Antioxidant from Natural Source)

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