Antioxidants

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Open AccessArticle

Effects of Zanthoxyli Pericarpium Extracts on Ligature-Induced Periodontitis and Alveolar Bone Loss in Rats

by Jang-Soo Kim, Beom-Rak Choi, Geun-Log Choi, Hye-Rim Park, Jin-Gwan Kwon, Chan-Gon Seo, Jae-Kwang Kim and Sae-Kwang Ku

Antioxidants 2025, 14(10), 1159; https://doi.org/10.3390/antiox14101159 - 24 Sep 2025

Abstract

Zanthoxyli Pericarpium (ZP), the dried pericarp of mature fruits of Zanthoxylum schinifolium Siebold and Zucc., has traditionally been used in East Asian medicine for its medicinal properties, but its therapeutic potential in periodontitis has not been elucidated. In the present study, we investigated [...] Read more.

Zanthoxyli Pericarpium (ZP), the dried pericarp of mature fruits of Zanthoxylum schinifolium Siebold and Zucc., has traditionally been used in East Asian medicine for its medicinal properties, but its therapeutic potential in periodontitis has not been elucidated. In the present study, we investigated the effects of ZP on ligature-induced experimental periodontitis (EPD) in male Sprague Dawley rats. Animals were assigned to vehicle control, ligature control, ZP-treated (25, 50, and 100 mg/kg), or indomethacin-treated (5 mg/kg) groups (n = 10 per group) and orally administered the respective treatments daily for 10 days after ligature placement. ZP significantly reduced anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissue. ZP suppressed the production of inflammatory mediators, such as tumor necrosis factor-α and interleukin-1β, in both gingival tissues and lipopolysaccharide-stimulated RAW 264.7 macrophages, through inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In addition, ZP decreased myeloperoxidase activity and reduced matrix metalloproteinase-8 expression, thereby preserving collagen areas. ZP also restored the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) balance, leading to a reduction in osteoclast numbers and their occupancy on the alveolar surface, and it effectively ameliorated horizontal alveolar bone loss. Furthermore, ZP exhibited antioxidant effects by lowering malondialdehyde levels and inducible nitric oxide synthase activity in gingival tissues. Statistical analysis was performed using ANOVA followed by a post hoc test, with significance set at p < 0.05. These findings indicate that ZP mitigates periodontitis through combined antimicrobial, anti-inflammatory, antioxidant, and anti-resorptive actions, supporting its potential as a therapeutic candidate for periodontitis. Full article

(This article belongs to the Special Issue Antioxidants as Weapons to Maintain or Restore Oral Health)

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Open AccessArticle

Organophosphate Pesticide Exposure and Semen Quality in Healthy Young Men: A Pilot Study

by Jenisha L. Stapleton, Sarah Adelman, Bobby B. Najari, Kurunthachalam Kannan, Vittorio Albergamo and Linda G. Kahn

Antioxidants 2025, 14(10), 1158; https://doi.org/10.3390/antiox14101158 - 24 Sep 2025

Abstract

This cross-sectional pilot study aimed to examine associations between urinary metabolites of organophosphate (OP) pesticides and semen quality in 42 healthy young men. Participants answered questionnaires, provided semen and urine samples, and had anthropometric measures taken. Urine and seminal plasma were assayed for [...] Read more.

This cross-sectional pilot study aimed to examine associations between urinary metabolites of organophosphate (OP) pesticides and semen quality in 42 healthy young men. Participants answered questionnaires, provided semen and urine samples, and had anthropometric measures taken. Urine and seminal plasma were assayed for dialkylphosphate (DAP) metabolites of OP pesticides using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Semen quality parameters were analyzed according to the World Health Organization protocol, and seminal oxidative stress was assayed using MiOXSYS, a galvanic cell-based technology that yields an integrated measure of oxidants and antioxidants. Associations of OP pesticide metabolites with continuous and dichotomous sperm concentration, percent motility, and percent normal morphology, and with seminal oxidative-reduction potential (ORP) were analyzed statistically. OP pesticide exposure was associated with lower overall semen quality. Specifically, ∑DAP metabolites, driven by diethyl metabolites, was inversely associated with percent sperm motility, but this relationship was not mediated by seminal ORP. Seminal ORP was inversely associated with sperm concentration, but OP pesticide exposure was not associated with seminal ORP. Full article

(This article belongs to the Special Issue Oxidative and Nitrosative Stress in Male Reproduction)

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Open AccessReview

Ferroptosis: The Initiation Process of Lipid Peroxidation in Muscle Food

by Joseph Kanner, Shpaizer Adi and Tirosh Oren

Antioxidants 2025, 14(10), 1157; https://doi.org/10.3390/antiox14101157 - 24 Sep 2025

Abstract

Animal slaughtering causes the cessation of oxygen delivery and that of nutrients such as cystine, glucose and others to muscle cells. In muscle cells, the changes in oxygen level and pH cause mitochondria, the endoplasmic reticulum, xanthine oxidase and uncoupled NOS to increase [...] Read more.

Animal slaughtering causes the cessation of oxygen delivery and that of nutrients such as cystine, glucose and others to muscle cells. In muscle cells, the changes in oxygen level and pH cause mitochondria, the endoplasmic reticulum, xanthine oxidase and uncoupled NOS to increase the level of O₂^•−, affecting the generation of H₂O₂ and the release of iron ions from ferritin. The activation of enzymes that remove and dislocate fatty acids from the membrane affects the sensitivity of muscle cells to peroxidation and ferroptosis. Increasing PUFAs in membrane phospholipids, by feeding animals a diet high in w-3 fatty acids, is a driving factor that increases lipid peroxidation and possible muscle ferroptosis. The activation of lipoxygenases by ROS to Fe³⁺-lipoxygenase increases hydroperoxide levels in cells. The labile iron pool generated by a “redox cycle” catalyzes phospholipid hydroperoxides to generate lipid electrophiles, proximate executioners of ferroptosis. Ferroptosis in food muscle cells is protected by high concentrations of vitamin E and selenium. In fresh muscle cells, glutathione peroxidase (GSH-PX) and other endogenous antioxidant enzymes are active and prevent lipid peroxidation; however, muscle heating eliminates enzymatic activities, making cells prone to high non-enzymatic lipid peroxidation. In muscle cells, coupled myoglobin and vitamin E act as a hydroperoxidase, preventing the generation of lipid electrophiles. Free iron ion chelators or effectors such as deferoxamine, EDTA, or ceruloplasmin are strong inhibitors of muscle cell lipid peroxidation, proving that muscle ferroptosis is mostly dependent on and catalyzed by the labile iron redox cycle. Full article

(This article belongs to the Topic Oxidative Stress and Diet: The Health Implications of Advanced Glycation and Lipid Oxidation End-Products)

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Open AccessReview

Host-Derived Reactive Oxygen Species in the Gut Epithelium: Defence Mechanism and Target of Bacterial Subversion

by Pranaya Kansakar, Subhadeep Gupta, Amirul Islam Mallick, Brendan W. Wren, Ezra Aksoy, Abdi Elmi and Ozan Gundogdu

Antioxidants 2025, 14(10), 1156; https://doi.org/10.3390/antiox14101156 - 24 Sep 2025

Abstract

Host physical, chemical, and immune responses constitute well-established defences against bacterial invasion. Recent studies have highlighted the critical role of cellular mechanisms, particularly the production of reactive oxygen species (ROS) in antibacterial defence. This review focuses on ROS generation by mammalian intestinal epithelial [...] Read more.

Host physical, chemical, and immune responses constitute well-established defences against bacterial invasion. Recent studies have highlighted the critical role of cellular mechanisms, particularly the production of reactive oxygen species (ROS) in antibacterial defence. This review focuses on ROS generation by mammalian intestinal epithelial cells (IECs) and investigates whether ROS production is host-driven to eliminate bacteria or manipulated by bacteria to suppress or exploit ROS for enhanced internalisation. We examine the activation mechanisms of the NADPH oxidase (NOX) enzyme complex and the resulting ROS production in IECs, which, unlike professional phagocytes, lack the ability to engulf bacteria. The downstream effects of NOX-mediated ROS signalling are discussed in detail. Additionally, we explore the dynamic interplay between host and pathogen, with particular attention to how bacterial infection may disrupt or hijack host NOX-mediated ROS responses. The review concludes with key experimental considerations and outlines future directions in this evolving field. Overall, we present ROS as a double-edged sword, an essential antimicrobial effector that is also susceptible to bacterial subversion, highlighting its potential as a target in novel antimicrobial strategies. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes—Second Edition)

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Open AccessArticle

14-Deoxy-11,12-didehydroandrographolide Alleviates IL-1β-Induced Insulin Resistance by Modulating NOX2-Driven ROS Generation and Restoring Insulin Signaling in 3T3-L1 Adipocytes

by Chih-Ching Yen, Chia-Wen Lo, Jyun-Lin Lee, Kai-Li Liu, Chien-Chun Li, Chong-Kuei Lii, Chia-En Hsu, Ya-Chen Yang and Haw-Wen Chen

Antioxidants 2025, 14(10), 1155; https://doi.org/10.3390/antiox14101155 - 24 Sep 2025

Abstract

Obesity is closely associated with the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM), primarily due to dysfunctional adipose tissue expansion and the secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β). 14-Deoxy-11,12-didehydroandrographolide (deAND), a major diterpenoid component of Andrographis paniculata, [...] Read more.

Obesity is closely associated with the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM), primarily due to dysfunctional adipose tissue expansion and the secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β). 14-Deoxy-11,12-didehydroandrographolide (deAND), a major diterpenoid component of Andrographis paniculata, has demonstrated notable antioxidant and anti-inflammatory activities. This study aimed to investigate the protective effects and mechanisms of deAND against IL-1β-induced IR in 3T3-L1 adipocytes. Network pharmacology analysis indicated that deAND targets several IR-related signaling pathways, particularly the MAPK and IRS-1/AKT pathways. The experimental results show that IL-1β stimulated p67phox membrane translocation and reactive oxygen species (ROS) production, contributing to impaired insulin signaling by activating ERK and JNK and reducing IRS-1/AKT phosphorylation, which ultimately decreased insulin-stimulated glucose uptake. Pretreatment with deAND effectively inhibited NOX2-derived ROS generation, suppressed ERK/JNK activation, restored IRS-1/AKT phosphorylation, and reversed the reduction in glucose uptake caused by IL-1β. These findings suggest that deAND can alleviate IR by inhibiting NOX2-mediated oxidative stress, restoring insulin signaling and improving glucose uptake, highlighting its potential as a therapeutic agent for obesity-related IR. Full article

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

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Open AccessReview

Involvement of Neuroinflammation and Oxidative Stress in L-DOPA-Induced Dyskinesia in Parkinson’s Disease: Role of Renin–Angiotensin System and ROCK Pathway

by Ana Muñoz, Andrea López-López, Jannette Rodríguez-Pallares and José Luis Labandeira-Garcia

Antioxidants 2025, 14(10), 1154; https://doi.org/10.3390/antiox14101154 - 23 Sep 2025

Abstract

Dopamine (DA) replacement by L-DOPA administration is the most common and effective treatment for Parkinson’s disease (PD). However, its chronic use leads to important side effects at advanced stages of the disease. Levodopa-induced dyskinesia (LID), characterized by involuntary, abnormal movements, is the main [...] Read more.

Dopamine (DA) replacement by L-DOPA administration is the most common and effective treatment for Parkinson’s disease (PD). However, its chronic use leads to important side effects at advanced stages of the disease. Levodopa-induced dyskinesia (LID), characterized by involuntary, abnormal movements, is the main challenge of L-DOPA treatment. Although the causes underlying LID are not fully understood, abnormal plasticity in corticostriatal synapses and dysregulated DA release from serotonin terminals play a crucial role. In recent years, several studies have suggested the involvement of neuroinflammation and oxidative stress in the pathophysiology of LID. Interestingly, different evidence has shown that blocking these pathways reduces LID in experimental animal PD models, pointing to the use of antioxidant/anti-inflammatory agents as a potential therapy for LID. Numerous studies have shown the role of the brain renin–angiotensin system (RAS) and the ROCK pathway in neuroinflammation and oxidative stress. Compounds acting through these routes have strong neuroprotective properties in PD models. Additionally, the use of ROCK inhibitors, such as fasudil, and RAS blockers has shown potent anti-dyskinetic effects. Therefore, compounds acting on the RAS and ROCK pathways could have a dual role, slowing down the degeneration of dopaminergic neurons and reducing the development of LID. Full article

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

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Open AccessArticle

Dexmedetomidine as a Protective Agent Against X-Ray Ionizing Radiation-Induced Small Intestinal Injury

by Süleyman Kalcan, Levent Tumkaya, Tolga Mercantepe, Hamit Yilmaz, Sibel Mataraci Karakas, Ahmet Pergel, Gokhan Demiral, Ali Ozdemir and Sema Rakici

Antioxidants 2025, 14(10), 1153; https://doi.org/10.3390/antiox14101153 - 23 Sep 2025

Abstract

Objective: This study was conducted to evaluate the potential radioprotective and therapeutic effects of dexmedetomidine (DEX), a selective α2-adrenergic receptor (α2AR) agonist, against ionizing X-ray-induced small intestinal injury in a dose-dependent manner. Methods: Male Sprague Dawley rats were randomly categorized into four groups. [...] Read more.

Objective: This study was conducted to evaluate the potential radioprotective and therapeutic effects of dexmedetomidine (DEX), a selective α2-adrenergic receptor (α2AR) agonist, against ionizing X-ray-induced small intestinal injury in a dose-dependent manner. Methods: Male Sprague Dawley rats were randomly categorized into four groups. These groups were the Control, Ionizing Radiation (IR, 8 Gy X-ray), IR+DEX 100 µg/kg, and IR+DEX 200 µg/kg. DEX was administered intraperitoneally to the treatment groups 30 min before radiation exposure. All groups were sacrificed 24 h following irradiation. Firstly, the small intestinal tissues were evaluated histopathologically (H&E staining). Subsequently, levels of malondialdehyde (MDA) and glutathione (GSH), as markers of oxidative stress, were measured, and immunohistochemical expression of Caspase-3 and 8-hydroxy-2′-deoxyguanosine (8-OHdG) was analyzed. Results: In the IR group, significant histopathological alterations were observed, including villus atrophy and villus loss due to fusion, crypt loss, and mucosal degeneration. Additionally, there was an increase in MDA levels, a decrease in GSH levels, and a marked elevation in the expression of Caspase-3 and 8-OHdG. In the DEX-treated groups, particularly at the 200 µg/kg dose, significant improvements were noted in these parameters. It was determined that the histological architecture was largely preserved, oxidative stress was reduced, and apoptosis was suppressed. Conclusion: The findings suggest that DEX may effectively reduce X-ray-induced small intestinal injury in a dose-dependent manner, and that this effect is mediated through antioxidant and anti-apoptotic mechanisms. DEX holds potential for the prevention or treatment of radiation-induced gastrointestinal toxicities. Full article

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Open AccessArticle

Transylvanian Grape Pomaces as Sustainable Sources of Antioxidant Phenolics and Fatty Acids—A Study of White and Red Cultivars

by Veronica Sanda Chedea, Liliana Lucia Tomoiagă, Mariana Ropota, Gabriel Marc, Floricuta Ranga, Maria Doinița Muntean, Alexandra Doina Sîrbu, Ioana Sorina Giurca, Maria Comșa, Ioana Corina Bocsan, Anca Dana Buzoianu, Hesham Kisher and Raluca Maria Pop

Antioxidants 2025, 14(10), 1152; https://doi.org/10.3390/antiox14101152 - 23 Sep 2025

Abstract

Grape pomace (GP), a significant by-product of winemaking, is gaining increasing recognition for its potential as a source of bioactive compounds with antioxidant and cardioprotective properties. This study aimed to characterize the polyphenolic profile, fatty acid composition, and antioxidant activity of 17 GP [...] Read more.

Grape pomace (GP), a significant by-product of winemaking, is gaining increasing recognition for its potential as a source of bioactive compounds with antioxidant and cardioprotective properties. This study aimed to characterize the polyphenolic profile, fatty acid composition, and antioxidant activity of 17 GP samples from Transylvanian cultivars. Polyphenolic content was determined using the Folin–Ciocalteu method and high-performance liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (HPLC–DAD–ESI MS) analysis. Fatty acid composition was analyzed using gas chromatography with flame ionization detection (GC–FID). Antioxidant capacity was assessed using five methods, which included the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2′-azino-bis (3-ethylbenzothialzoline-6-sulfonic acid) (ABTS) radical scavenging, ferric-reducing antioxidant power (FRAP), cupric ion reducing antioxidant capacity (CUPRAC), and reducing power (RP) assays. Additionally, all extracts were analyzed by Fourier transform infrared (FTIR) spectroscopy to identify the presence of functional groups and chemical bonds associated with bioactive compounds. The results showed that Neuburger (NE), Radames (RA), and Regent (RE) cultivars had the highest phenolic concentrations, particularly of catechin, epicatechin, and procyanidin dimers. NE and Feteascǎ Regalǎ (FR) exhibited the greatest radical scavenging and electron transfer activities across multiple antioxidant assays. Rose Blaj (RB) and Astra (AS) displayed the most favorable fatty acid profiles, with high unsaturated-to-saturated fatty acid (UFA/SFA) and hypocholesterolemic-to-hypercholesterolemic fatty acid (H/H) ratios, as well as low atherogenicity (AI) and thrombogenicity (TI) indices, suggesting cardioprotective potential. Additionally, RB and NE cultivars also demonstrated a strong chelation of Cu²⁺ and Fe²⁺ ions, enhancing their antioxidant efficacy by mitigating metal-catalyzed oxidative stress. These findings underscore the potential of GP, particularly from NE, RB, RA, and AS cultivars, the last three of which were homologated in Transylvania at SCDVV Blaj, as valuable sources of health-promoting compounds for use in food, nutraceuticals, and other health-related applications. Full article

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

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Open AccessArticle

Light-Induced Transcription in Zebrafish Targets Mitochondrial Function and Heme Metabolism

by Alessandra Boiti, Hanna T. Weber, Yuhang Hong, Rima Siauciunaite, Sebastian G. Gornik, Nicholas S. Foulkes and Daniela Vallone

Antioxidants 2025, 14(10), 1151; https://doi.org/10.3390/antiox14101151 - 23 Sep 2025

Abstract

In fish cells, light exposure elevates levels of reactive oxygen species (ROS) and stress-activated MAP kinase activity and thereby induces gene transcription. However, we lack a complete understanding of the function and evolution of this regulatory mechanism. Here, we reveal that a set [...] Read more.

In fish cells, light exposure elevates levels of reactive oxygen species (ROS) and stress-activated MAP kinase activity and thereby induces gene transcription. However, we lack a complete understanding of the function and evolution of this regulatory mechanism. Here, we reveal that a set of mitochondrial and heme metabolism genes is transcriptionally induced in zebrafish cells upon exposure to light or elevated ROS. The integrity of D-box and E-box enhancers in these gene promoters is essential for their transcriptional activation. Furthermore, light-induced transcription of mitochondrial and heme metabolism genes is absent in a cell line derived from the blind Somalian cavefish (Phreatichthys andruzzii). This fish species has evolved in perpetual darkness and lacks light-dependent circadian and DNA repair responses as well as D-box-mediated and light- and ROS-induced transcription. PAR-bZip transcription factors bind to and activate transcription via the D-box. Cavefish homologs of these factors share extensive homology with their zebrafish counterparts and lack the deletion mutations that characterize other light-dependent genes in this species. These results extend the role of the D-box as a key regulator of light- and ROS-driven transcription in fish, beyond the circadian clock and DNA repair systems, to also encompass metabolic and mitochondrial function. Full article

(This article belongs to the Special Issue Reactive Oxygen Species Signalling and Oxidative Stress in Fish)

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Open AccessArticle

Red Blood Cell Antioxidant State in Fanconi Anemia: The Highlighted Roles of Pi-Class Glutathione S-Transferase and Glutathione Peroxidase

by Cláudia Oliveira, Ricardo Jorge Dinis-Oliveira, Félix Carvalho, Paula Jorge and Beatriz Porto

Antioxidants 2025, 14(10), 1150; https://doi.org/10.3390/antiox14101150 - 23 Sep 2025

Abstract

Fanconi anemia (FA) is a rare bone marrow failure disorder characterized at the cellular level by hypersensitivity to alkylating agents, such as diepoxybutane (DEB), and redox imbalance. Alterations in red blood cells (RBCs), which play a key role in systemic antioxidant defense, are [...] Read more.

Fanconi anemia (FA) is a rare bone marrow failure disorder characterized at the cellular level by hypersensitivity to alkylating agents, such as diepoxybutane (DEB), and redox imbalance. Alterations in red blood cells (RBCs), which play a key role in systemic antioxidant defense, are among the earliest changes in FA, consistent with an oxidative stress (OS) profile. Previous studies about antioxidant activity in RBCs from these patients are scarce and inconsistent. This study aimed to better understand the antioxidant profile in RBCs from FA patients carrying the homozygous FANCA c.295C>T variant. Glutathione content and the activities of catalase, superoxide dismutase, glutathione peroxidase (GPx), and Pi-class glutathione S-transferase (GSTP1) were quantified, both at baseline and after culture with and without DEB, in RBCs from FA patients, FA carriers, and controls. At baseline, FA RBCs displayed significantly reduced catalase activity, whereas GPx and GSTP1 activities were significantly increased, suggesting an OS preconditioning state, not observed in RBCs from FA carriers and controls. Under culture and DEB exposure, FA RBCs exhibited a significant decline in both GSTP1 and GPx activities, contrary to controls. These new findings highlight a key role of GSTP1 and GPx activities in baseline antioxidant defense, severely compromised in case of increased OS toxicity. Full article

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

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Open AccessArticle

Effect of Different Interstocks on Fruit Quality, Amino Acids, and Antioxidant Capacity in ‘Yuanxiaochun’ Citrus

by Tie Wang, Guochao Sun, Siya He, Ling Liao, Bo Xiong and Zhihui Wang

Antioxidants 2025, 14(10), 1149; https://doi.org/10.3390/antiox14101149 - 23 Sep 2025

Abstract

High grafting is a widely recognized technique for varietal renewal in aging citrus orchards. However, following high grafting, a specific ‘rootstock-interstock-scion’ combination is formed, yet the influence of interstock on scion fruit quality remains insufficiently explored. To address this gap, we conducted experiments [...] Read more.

High grafting is a widely recognized technique for varietal renewal in aging citrus orchards. However, following high grafting, a specific ‘rootstock-interstock-scion’ combination is formed, yet the influence of interstock on scion fruit quality remains insufficiently explored. To address this gap, we conducted experiments by grafting ‘Yuanxiaochun’ ((Citrus unshiu Marcov × Citrus sinensis Osbeck) × (Citrus reticulata × Citrus paradisi)) onto three distinct interstocks (‘Yuanxiaochun’/‘Harumi’/‘Trifoliate orange’ (CJ), ‘Yuanxiaochun’/‘Ponkan’/‘Trifoliate orange’ (PG), ‘Yuanxiaochun’/‘Marumi Kumquat’/‘Trifoliate orange’ (JJ)), with ‘Yuanxiaochun’/‘Trifoliate orange’ used as a control (CK), and comprehensively evaluated their impact on fruit quality of ‘Yuanxiaochun’. Our research results show that interstock significantly increased the total soluble solids (TSSs) content of fruit. Additionally, interstocks also significantly increased the organic acid content in the fruit, particularly citric acid, which was on average 2.90 mg·g⁻¹ FW higher than CK. In terms of fruit flavor, interstocks significantly reduced the sugar/acid ratio and the sweetness/total acid ratio. However, CJ and PG showed markedly higher sweetness levels. Furthermore, interstocks led to a marked increase in both total amino acid content and flavor-active amino acid content in the fruit. Taste active values of γ-aminobutyric acid, asparagine, aspartic acid, glutamic acid, and arginine were all greater than 1, indicating a significant contribution to the fruit flavor. Moreover, interstocks increased the total flavonoid and phenol content in the fruit, thereby affecting its overall antioxidant capacity. These findings provide valuable and systematic insights for high grafting and variety renewal in citrus production. Full article

(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)

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Open AccessReview

The Impact of Air Pollution on the Lung–Gut–Liver Axis: Oxidative Stress and Its Role in Liver Disease

by Jacopo Iaccarino, Irene Mignini, Rossella Maresca, Gabriele Giansanti, Giorgio Esposto, Raffaele Borriello, Linda Galasso, Maria Elena Ainora, Antonio Gasbarrini and Maria Assunta Zocco

Antioxidants 2025, 14(10), 1148; https://doi.org/10.3390/antiox14101148 - 23 Sep 2025

Abstract

The expression “lung–gut–liver axis” refers to the interconnected processes occurring in the lungs, gastrointestinal tract, and liver, particularly in relation to immune function, microbial regulation, and metabolic responses. Over the past decade, growing concern has emerged regarding the detrimental impact of air pollution [...] Read more.

The expression “lung–gut–liver axis” refers to the interconnected processes occurring in the lungs, gastrointestinal tract, and liver, particularly in relation to immune function, microbial regulation, and metabolic responses. Over the past decade, growing concern has emerged regarding the detrimental impact of air pollution on liver disease. Air pollutants, including particulate matter (PM) and chemical gases such as nitrogen oxides (NOx), can influence the microbiome in the lungs and gut by generating reactive oxygen species (ROS), which induce oxidative stress and local inflammation. This redox imbalance leads to the production of altered secondary microbial metabolites, potentially disrupting both the alveolar–capillary and gut barriers. Under these conditions, microbes and their metabolites can translocate to the liver, triggering inflammation and contributing to liver diseases, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, and hepatocellular carcinoma (HCC). This manuscript aims to review recent findings on the impact of air pollution on liver disease pathogenesis, exploring the molecular, genetic, and microbiome-related mechanisms underlying lung–gut–liver interactions, providing insights into potential strategies to prevent or mitigate liver disease progression. Full article

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

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Open AccessArticle

Atorvastatin Induces Bioenergetic Impairment and Oxidative Stress Through Reverse Electron Transport

by Francesca Valenti, Luca Pincigher, Nicola Rizzardi, Francesca Orsini, Christian Bergamini and Romana Fato

Antioxidants 2025, 14(10), 1147; https://doi.org/10.3390/antiox14101147 - 23 Sep 2025

Abstract

Statins are the first-line therapy for managing elevated cholesterol levels that represent a risk of acute cardiovascular events. However, the use of statins is associated with several side effects, likely due to the depletion of Coenzyme Q₁₀ (CoQ₁₀), a key [...] Read more.

Statins are the first-line therapy for managing elevated cholesterol levels that represent a risk of acute cardiovascular events. However, the use of statins is associated with several side effects, likely due to the depletion of Coenzyme Q₁₀ (CoQ₁₀), a key component of the mitochondrial electron transport chain and a membrane antioxidant. In our study, we present evidence of the cytotoxic effects of Atorvastatin on human dermal fibroblasts in terms of oxidative stress and mitochondrial impairment. Interestingly, CoQ₁₀ supplementation in statin-treated cells significantly reduced ROS levels and restored mitochondrial oxygen consumption rate and the intracellular ATP/ADP ratio. Moreover, our data suggest that the mechanism for Atorvastatin off-target effects at high concentrations involves the inhibition of respiratory complexes I and III, leading to reverse electron transport and ROS production by Complex I. These findings highlight the potential benefits of CoQ₁₀ supplementation in mitigating statin-induced cytotoxicity and propose a mechanistic basis for the adverse effects associated with Atorvastatin therapy. Full article

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

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Open AccessCommunication

Plasma Glycated and Oxidized Amino Acid-Based Screening Test for Clinical Early-Stage Osteoarthritis

by Aisha Nasser J. M. Al-Saei, Usman Ahmed, Edward J. Dickenson, Kashif Rajpoot, Mingzhan Xue, Essam M. Abdelalim, Abdelilah Arredouani, Omar M. E. Albagha, Damian R. Griffin, Paul J. Thornalley and Naila Rabbani

Antioxidants 2025, 14(10), 1146; https://doi.org/10.3390/antiox14101146 - 23 Sep 2025

Abstract

The diagnosis of early-stage osteoarthritis (eOA) is important in disease management and outcomes. Herein we report the clinical validation of a blood test for the diagnosis of eOA in a large patient cohort using trace-level glycated and oxidized amino acid analytes. Subjects were [...] Read more.

The diagnosis of early-stage osteoarthritis (eOA) is important in disease management and outcomes. Herein we report the clinical validation of a blood test for the diagnosis of eOA in a large patient cohort using trace-level glycated and oxidized amino acid analytes. Subjects were recruited and enrolled in two study groups: subjects with eOA of the hip (n = 110) and asymptomatic controls (n = 120). Their plasma was analyzed for glycated and oxidized amino acids by quantitative liquid chromatography–tandem mass spectrometry. Algorithms were developed using plasma hydroxyproline and 12 glycated and oxidized amino acid analyte features to classify the subjects with eOA and asymptomatic controls. The accuracy was defined as the percentage of the subjects correctly classified in the test set validation. The minimum number of analyte features required for the optimum accuracy was five glycated amino acid analytes: N_ω-carboxymethyl-arginine, hydroimidazolones derived from glyoxal, methylglyoxal and 3-deoxyglucosone, and glucosepane. The classification performance metrics included an accuracy of 95%, sensitivity of 96%, specificity of 94%, area under the curve of the receiver operating characteristic curve of 99%, and positive and negative predictive values of 94% and 97%. We concluded that an assay of five trace-level glycated amino acids present in plasma can provide a simple blood test for the screening of eOA. This is predicted to improve the case identification for expert referral 9-fold. 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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Open AccessArticle

Shikimic Acid Mitigates Deoxynivalenol-Induced Jejunal Barrier Injury in Mice via Activation of the Nrf-2/HO-1/NQO1 Pathway and Modulation of Gut Microbiota

by Yijing Su, Bin Zheng, Chixiang Zhou, Miaochun Li, Yifeng Yuan, Han Wang, Bei Li, Shiyu Wu, Zhengkun Wu, Yinquan Zhao, Wei Zhang and Gang Shu

Antioxidants 2025, 14(10), 1145; https://doi.org/10.3390/antiox14101145 - 23 Sep 2025

Abstract

Deoxynivalenol (DON), a mycotoxin from Fusarium that contaminates cereals, can also induce intestinal injury. However, the mechanisms underlying DON-induced jejunal barrier injury remain unclear. This study demonstrates that shikimic acid (SA) alleviates DON-induced jejunal barrier damage and dysbiosis via antioxidant pathways. Fifty 5-week-aged [...] Read more.

Deoxynivalenol (DON), a mycotoxin from Fusarium that contaminates cereals, can also induce intestinal injury. However, the mechanisms underlying DON-induced jejunal barrier injury remain unclear. This study demonstrates that shikimic acid (SA) alleviates DON-induced jejunal barrier damage and dysbiosis via antioxidant pathways. Fifty 5-week-aged male KM mice were divided into control (CON), model (MOD, 2.4 mg/kg bw DON), and SA-treated groups (LDG/MDG/HDG: 25/50/100 mg/kg bw SA + DON). After SA treatment, notably MDG, reversed DON-induced weight loss and jejunal hyperemia; ameliorated villus atrophy, crypt deepening and goblet cell loss, increasing villus/crypt ratio; reduced gut permeability markers (D-LA/DAO) and pro-inflammatory cytokines (TNF-α/IL-6/IL-1β); and dose-dependently upregulated tight junction proteins (ZO-1/Occludin/Claudin1). Mechanistically, SA activated the Nrf2/HO-1/NQO1 pathway, elevating antioxidants (GSH/SOD/AOC) while reducing MDA, with MDG showing optimal efficacy. 16S rRNA sequencing revealed MDG counteracted DON-induced dysbiosis by enriching beneficial bacteria (e.g., Bacteroidota at phylum level; Muribaculaceae at family level) and suppressing pathogens (Staphylococcaceae) (LDA score > 4.0). Thus, SA mitigates DON toxicity via Nrf2-mediated barrier restoration, anti-inflammation, and microbiota modulation. This research provides new insights for the further development of Shikimic Acid and the treatment of DON-induced jejunal barrier injury. Full article

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22 pages, 2458 KB

Open AccessArticle

Betulinic Acid-Enriched Dillenia indica L. Bark Extract Attenuates UVB-Induced Skin Aging via KEAP1-Mediated Antioxidant Pathways

by Bo-Rim Song, Sunghwan Kim and Sang-Han Lee

Antioxidants 2025, 14(9), 1144; https://doi.org/10.3390/antiox14091144 - 22 Sep 2025

Abstract

The bark of Dillenia indica L. is a rich source of phenolic and triterpenoid compounds, including betulinic acid (BA), known for their antioxidant and anti-aging properties. This study investigated the antioxidant potential of a BA-enriched extract through a multidisciplinary approach combining computational, experimental, [...] Read more.

The bark of Dillenia indica L. is a rich source of phenolic and triterpenoid compounds, including betulinic acid (BA), known for their antioxidant and anti-aging properties. This study investigated the antioxidant potential of a BA-enriched extract through a multidisciplinary approach combining computational, experimental, and cell-based evaluations. Molecular docking and molecular dynamics simulations revealed that BA binds stably to Kelch-like ECH-associated protein 1 (KEAP1), suggesting activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Extraction conditions were optimized using response surface methodology (RSM) and artificial neural network (ANN) modeling, yielding the maximum total phenolic content (TPC; 85.33 ± 2.26 mg gallic acid equivalents/g) and total flavonoid content (TFC; 75.60 ± 1.66 mg catechin equivalents/g), with ANN demonstrating superior predictive performance compared to RSM. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) confirmed the presence of BA in the optimized extract. Simulated gastrointestinal digestion revealed reductions in TPC, TFC, and radical scavenging activity during the gastric phase. In ultraviolet B (UVB)-irradiated human keratinocyte (HaCaT) cells, the optimized extract significantly reduced intracellular reactive oxygen species (ROS) and upregulated the KEAP1-Nrf2-heme oxygenase-1 (HO-1) pathway, confirming its antioxidant mechanism. These findings highlight the extract’s stability, bioactivity, and mechanistic efficacy, supporting its application as a nutraceutical ingredient for combating oxidative stress and skin aging. Full article

(This article belongs to the Special Issue Antioxidants and Oxidative Stress in Skin Health and Diseases)

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23 pages, 1267 KB

Open AccessArticle

Dysregulated Expression of Canonical and Non-Canonical Glycolytic Enzyme Isoforms in Peripheral Blood from Subjects with Alcohol Use Disorder and from Individuals with Acute Alcohol Consumption

by Maura Rojas-Pirela, Daniel Salete-Granado, Diego Andrade-Alviárez, Alejandro Prieto-Rojas, Cristina Rodríguez, María-Lourdes Aguilar-Sánchez, David Puertas-Miranda, María-Ángeles Pérez-Nieto, Vanessa Rueda-Cala, Candy Pérez, Wilfredo Quiñones, Paul A. M. Michels, Ángeles Almeida and Miguel Marcos

Antioxidants 2025, 14(9), 1143; https://doi.org/10.3390/antiox14091143 - 22 Sep 2025

Abstract

Glycolysis is primarily involved in ATP production but also modulates oxidative stress. Chronic alcohol consumption is correlated with an increased incidence of multiple diseases, including cancer and neurodegenerative diseases (NDDs), though the underlying mechanisms remain unclear. Guided by a literature review and bioinformatics [...] Read more.

Glycolysis is primarily involved in ATP production but also modulates oxidative stress. Chronic alcohol consumption is correlated with an increased incidence of multiple diseases, including cancer and neurodegenerative diseases (NDDs), though the underlying mechanisms remain unclear. Guided by a literature review and bioinformatics analysis, we evaluated the expression of 22 genes encoding various isoforms of seven glycolytic enzymes (GEs) in the peripheral blood of patients with alcohol use disorder (AUD), individuals with acute alcohol consumption (AAC), and their respective control groups using qPCR. In parallel, we evaluated the expression of selected genes coding for GEs linked to NDDs, as well as astrocytic markers in primary mouse astrocyte cultures exposed to ethanol. Thirteen GE-related genes, including non-canonical isoforms, were significantly dysregulated in AUD patients; notably, eight of these genes showed similar alterations in individuals with AAC. Several enzymes encoded by these genes are known to be regulated by oxidative stress. Ethanol-exposed astrocytes also showed altered expression of glycolytic genes associated with NDDs and astrocyte function. These findings indicate that glycolytic dysregulation is driven by ethanol intake, regardless of exposure duration or organic damage, highlighting a link between ethanol-driven redox imbalance and glycolytic remodeling, which could contribute to organ damage. Full article

(This article belongs to the Special Issue Alcohol-Induced Oxidative Stress in Health and Disease, 2nd Edition)

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38 pages, 2022 KB

Open AccessReview

Beyond Antioxidants: How Redox Pathways Shape Cellular Signaling and Disease Outcomes

by Abdallah Alhaj Sulaiman and Vladimir L. Katanaev

Antioxidants 2025, 14(9), 1142; https://doi.org/10.3390/antiox14091142 - 22 Sep 2025

Abstract

Cellular redox pathways are critical regulators of various biological processes, including the intricate modulation of intracellular signaling pathways. This review explores how major redox enzymes—such as catalase, superoxide dismutases, glutathione peroxidases, thioredoxins, and peroxiredoxins—interact with key cellular signaling pathways, including receptor tyrosine kinase, [...] Read more.

Cellular redox pathways are critical regulators of various biological processes, including the intricate modulation of intracellular signaling pathways. This review explores how major redox enzymes—such as catalase, superoxide dismutases, glutathione peroxidases, thioredoxins, and peroxiredoxins—interact with key cellular signaling pathways, including receptor tyrosine kinase, mTORC1/AMPK, Wnt/β-catenin, TGF-β/SMAD, NF-κB, Hedgehog, Notch, and GPCR signaling. By investigating mechanisms such as ROS-mediated activation, cysteine oxidation, spatial enzyme localization, and phosphatase regulation, we demonstrate the extensive influence of redox balance on cellular signaling dynamics. Understanding these redox-dependent interactions provides insights into pathophysiological conditions ranging from cancer to fibrosis, offering novel therapeutic opportunities. Full article

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

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21 pages, 4454 KB

Open AccessArticle

Modulation of Pulmonary Inflammation and the Redox Pathway In Vitro and In Vivo by Fumaric Ester

by Aline Pontes de Oliveira, Alexsandro Tavares Figueiredo-Junior, Priscilla Cristine de Oliveira Mineiro, Evelyn Caribé Mota, Carolinne Souza de Amorim, Helber da Maia Valenca, Aline Cristina Casimiro de Albuquerque Gomes, Sabrina Sodré de Souza Serra, Pedro Leme Silva, Christina Maeda Takiya, João Alfredo de Moraes, Samuel Santos Valenca and Manuella Lanzetti

Antioxidants 2025, 14(9), 1141; https://doi.org/10.3390/antiox14091141 - 22 Sep 2025

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary inflammation and the destruction of the pulmonary parenchyma (emphysema), with only symptomatic treatment available. Molecules with antioxidant and anti-inflammatory properties, such as dimethyl fumarate (DMF), have shown therapeutic potential. This study evaluated the [...] Read more.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary inflammation and the destruction of the pulmonary parenchyma (emphysema), with only symptomatic treatment available. Molecules with antioxidant and anti-inflammatory properties, such as dimethyl fumarate (DMF), have shown therapeutic potential. This study evaluated the effects of DMF and its metabolite, monomethyl fumarate (MMF), on pulmonary inflammation induced by cigarette smoke (in vitro) and porcine pancreatic elastase (PPE) in mice (in vivo). In vitro, human pulmonary epithelial cells (PC-9) were treated with MMF at concentrations of 10, 30, and 100 µM and exposed to cigarette smoke extract (CSE) to assess cell viability, oxidative stress (ROS), lipid peroxidation, and nitrite production. In vivo, C57BL/6 mice were treated with DMF (30 and 100 mg/kg) during and after the induction of emphysema by PPE. ROS levels, total cell count in bronchoalveolar lavage fluid (BALF), lung histology, and the expression of oxidative stress proteins (SOD1 and HO-1) were analyzed. MMF reduced oxidative stress and lipid peroxidation under in vitro conditions. In vivo, DMF reduced ROS levels, inflammation, and prevented lung damage, such as alveolar enlargement. The expression of SOD1 and HO-1 was modulated by DMF treatment. The results suggest that DMF could be an effective therapeutic alternative for COPD, reducing oxidative stress and inflammation. Full article

(This article belongs to the Special Issue Redox Regulation in COPD: Therapeutic Implications of Antioxidants)

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