Antioxidants

19 pages, 4136 KB

Open AccessArticle

Neuroprotective Effects of N-Acetylcysteine-Amide (AD4) in a Survival Mouse Model of Paraoxon Intoxication: Targeting Oxidative Stress, Neuroinflammation and Memory Impairments

by Edurne Urquizu, Marine Cuiller, Georgia Papadopoulou, David Pubill, Demetrio Raldúa, Jordi Camarasa, Elena Escubedo and Raul López-Arnau

Antioxidants 2025, 14(12), 1463; https://doi.org/10.3390/antiox14121463 (registering DOI) - 6 Dec 2025

Abstract

Neurotoxicity induced by organophosphorus (OP) compounds such as paraoxon (POX) leads to severe brain damage and cognitive impairments. Although current treatments alleviate acute cholinergic symptoms, they fail to address secondary neurotoxicity. This study investigated the therapeutic potential of N-acetylcysteine-amide (AD4), a blood–brain-barrier permeable [...] Read more.

Neurotoxicity induced by organophosphorus (OP) compounds such as paraoxon (POX) leads to severe brain damage and cognitive impairments. Although current treatments alleviate acute cholinergic symptoms, they fail to address secondary neurotoxicity. This study investigated the therapeutic potential of N-acetylcysteine-amide (AD4), a blood–brain-barrier permeable antioxidant, in a survival mouse model of acute POX intoxication. Male Swiss CD-1 mice received POX (4 mg/kg) followed by standard emergency therapy (atropine, pralidoxime and diazepam). AD4 (150 mg/kg) was administered 2 and 6 h post-exposure. AD4 treatment effectively prevented oxidative stress by reducing lipid peroxidation and restoring the expression in hippocampus (HP) and/or prefrontal cortex (PFC) of key antioxidant enzymes such as glutathione peroxidase-1 (GPx-1) and catalase (CAT) suppressed by POX acute exposure. Moreover, AD4 attenuated neuroinflammation in specific hippocampal subregions, as evidenced by reduced Glial Fibrillary Acidic Protein (GFAP) and Ionized Calcium Binding Adaptor Molecule 1 (Iba-1) immunoreactivity. Importantly, AD4 also rescued recognition memory deficits, as assessed by the Novel Object Recognition Test (NORT). In summary, these findings demonstrate that AD4 mitigates oxidative stress, neuroinflammation, and cognitive dysfunction following acute POX intoxication, supporting its potential as an adjuvant therapy for mitigating the secondary neurotoxicity derived from organophosphorus poisoning. Full article

(This article belongs to the Special Issue Inhibition of Oxidative Stress and Related Signaling Pathways in Neuroprotection—2nd Edition)

► Show Figures

Figure 1

24 pages, 895 KB

Open AccessReview

Reprogramming the Mitochondrion in Atherosclerosis: Targets for Vascular Protection

by Patrycja Anna Glogowski, Federica Fogacci, Cristina Algieri, Antonia Cugliari, Fabiana Trombetti, Salvatore Nesci and Arrigo Francesco Giuseppe Cicero

Antioxidants 2025, 14(12), 1462; https://doi.org/10.3390/antiox14121462 - 5 Dec 2025

Abstract

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, with a substantial proportion of events occurring prematurely. Atherosclerosis (AS), the central driver of cardiovascular pathology, results from the convergence of metabolic disturbances, vascular inflammation, and organelle dysfunction. Among intracellular organelles, mitochondria have [...] Read more.

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, with a substantial proportion of events occurring prematurely. Atherosclerosis (AS), the central driver of cardiovascular pathology, results from the convergence of metabolic disturbances, vascular inflammation, and organelle dysfunction. Among intracellular organelles, mitochondria have emerged as critical regulators of vascular homeostasis. Beyond their canonical role in adenosine triphosphate (ATP) production, mitochondrial dysfunction—including impaired mitochondrial oxidative phosphorylation (OXPHOS), excessive generation of reactive oxygen species (ROS), accumulation of mitochondrial DNA (mtDNA) damage, dysregulated dynamics, and defective mitophagy—contributes to endothelial dysfunction, vascular smooth muscle cell (VSMC) phenotypic switching, macrophage polarization, and ultimately plaque initiation and destabilization. These insights have established the rationale for mitochondrial “reprogramming”—that is, the restoration of mitochondrial homeostasis through interventions enhancing biogenesis, dynamics, and quality control—as a novel therapeutic paradigm. Interventions that enhance mitochondrial biogenesis, restore mitophagy, and rebalance fission–fusion dynamics are showing promise in preclinical models of vascular injury. A growing array of translational strategies—including small-molecule activators such as resveratrol and Mitoquinone (MitoQ), gene-based therapies, and nanoparticle-mediated drug delivery systems—are under active investigation. This review synthesizes current mechanistic knowledge on mitochondrial dysfunction in ASand critically appraises therapeutic approaches aimed at vascular protection through mitochondrial reprogramming. Full article

(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunction in Metabolic Disorders)

18 pages, 23386 KB

Open AccessArticle

Cistanche deserticola Polysaccharides Protect Against Doxorubicin-Induced Cardiotoxicity via Antioxidant and Mitochondrial Mechanisms

by Jingyi Qi, Yang Zhang, Mingyang Cui, Yufang Shi, Xinyu Luo, Chang Fan, Sitong Wan, Peng An, Yongting Luo and Junjie Luo

Antioxidants 2025, 14(12), 1461; https://doi.org/10.3390/antiox14121461 - 5 Dec 2025

Abstract

Doxorubicin (DOX), a clinical broad-spectrum anthracycline chemotherapeutic agent, induces dose-dependent cardiotoxicity that progresses to heart failure (HF), thereby severely limiting its clinical application. Mitochondrial dysfunction and oxidative stress dysregulation are core pathological mechanisms underlying DOX-induced myocardial injury. This study aimed to investigate the [...] Read more.

Doxorubicin (DOX), a clinical broad-spectrum anthracycline chemotherapeutic agent, induces dose-dependent cardiotoxicity that progresses to heart failure (HF), thereby severely limiting its clinical application. Mitochondrial dysfunction and oxidative stress dysregulation are core pathological mechanisms underlying DOX-induced myocardial injury. This study aimed to investigate the protective effect and underlying mechanism of Cistanche deserticola polysaccharides (CDPs) against DOX-induced cardiotoxicity in C57BL/6J mice. Compared with the DOX model group, CDPs significantly increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and reduced the activities of serum creatine kinase (CK), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). Additionally, CDPs notably decreased the malondialdehyde (MDA) levels in serum and myocardial tissue, while significantly enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, CDPs ameliorated mitochondrial swelling and crista fracture, upregulated the expression of mitochondrial respiratory chain complex-related genes, and increased adenosine triphosphate (ATP) production. In conclusion, CDPs alleviate DOX-induced cardiotoxicity and protect cardiac function by inhibiting myocardial oxidative stress and improving mitochondrial function, which provides a potential therapeutic strategy for preventing DOX-related cardiotoxicity. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Diseases)

27 pages, 1690 KB

Open AccessReview

Conventional and Advanced Processing Techniques and Their Effect on the Nutritional Quality and Antinutritional Factors of Pearl Millet Grains: The Impact on Metabolic Health

by Letícia da Silva Oliveira Moura, Rita de Cássia Avellaneda Guimarães, Aline Carla Inada, Juliana Rodrigues Donadon, Arnildo Pott, Rosângela dos Santos Ferreira, Carolina Di Pietro Fernandes, Caroline de Moura Costa, Fernando dos Santos Moura, Karine de Cássia Freitas, Danielle Bogo, Valter Aragão do Nascimento and Priscila Aiko Hiane

Antioxidants 2025, 14(12), 1460; https://doi.org/10.3390/antiox14121460 - 5 Dec 2025

Abstract

Food processing techniques are widely used in the food industry to ensure food safety, extend shelf life, and enhance sensory appeal without compromising the product’s nutritional quality. Pearl millet, which is considered a “nutricereal”, features essential content of proteins, soluble and insoluble fibers, [...] Read more.

Food processing techniques are widely used in the food industry to ensure food safety, extend shelf life, and enhance sensory appeal without compromising the product’s nutritional quality. Pearl millet, which is considered a “nutricereal”, features essential content of proteins, soluble and insoluble fibers, minerals (e.g., iron, zinc, and magnesium), bioactive compounds (e.g., phenolic acids, flavonoids, and carotenoids), and antinutritional factors (e.g., phytic acid, C-glycosyl flavones, tannins, and non-digestible oligosaccharides). This nutricereal also undergoes processing methods to improve or maintain its nutritional quality while simultaneously reducing antinutritional factors. Pearl millet processing techniques are categorized into conventional (or traditional) and advanced methods; however, a knowledge gap exists in studies evaluating the post-processing of pearl millet and its impact on metabolic health in in vivo and in vitro experimental models. This study aims to demonstrate the principal conventional and advanced processing techniques used in pearl millet, how they can ensure nutritional quality and reduce antinutritional factors, and how the final post-processing product could impact metabolic health. Full article

(This article belongs to the Special Issue Antioxidant Activities of Phytochemicals in Fruits and Vegetables)

► Show Figures

Figure 1

18 pages, 2935 KB

Open AccessArticle

Effects of Short-Term Feeding of Resveratrol on Growth Performance, Meat Quality, Antioxidant Capacity, Serum Biochemical Parameters and Intestinal Health in Yellow-Feathered Broilers Under Dexamethasone-Induced Oxidative Stress

by Hui Ye, Yangyu Wang, Huilan Zhu, Chao Huang, Weiwei Wang, Yifan Jia, Zhaoheng Hu, Huiyun Zhou, Shujie Liang, Chong Ling, Changming Zhang, Zemin Dong and Jianjun Zuo

Antioxidants 2025, 14(12), 1459; https://doi.org/10.3390/antiox14121459 - 5 Dec 2025

Abstract

Oxidative stress is believed to deteriorate production performance and cause substantial economic losses in commercial poultry farming. Resveratrol (RES) is a polyphenolic antioxidant that can improve intestinal barrier function and regulate gut microbiota composition. This study aimed to evaluate whether short-term (14 days) [...] Read more.

Oxidative stress is believed to deteriorate production performance and cause substantial economic losses in commercial poultry farming. Resveratrol (RES) is a polyphenolic antioxidant that can improve intestinal barrier function and regulate gut microbiota composition. This study aimed to evaluate whether short-term (14 days) dietary resveratrol (1000–3000 mg/kg) mitigates dexamethasone (DEX)-induced oxidative stress and performance loss in yellow-feathered broilers. Two hundred and forty 52-day-old birds were assigned to five treatments (n = 8 pens × 6). Control (CON) and DEX groups received the basal diet; DR1, DR2 and DR3 were provided with the basal diet plus 1000, 2000 or 3000 mg/kg RES. During days 1–5, the DEX and RES (DR1, DR2 and DR3) groups were intraperitoneally injected with 5 mg/kg BW DEX; CON birds received saline. DEX significantly reduced average daily gain (ADG) and raised feed conversion ratio (FCR) (p < 0.05) without altering feed intake. RES at 1000–2000 mg/kg improved ADG, reduced FCR and lowered serum corticosterone and blood urea nitrogen while increasing albumin (p < 0.05). DEX elevated malondialdehyde (MDA) in liver and thigh muscle, suppressed liver catalase (CAT) activity, and suppressed thigh muscle superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and CAT activities. In serum, only SOD activity decreased. RES partially alleviated the abnormal changes in these antioxidant indices. Intestinally, DEX increased MDA, shortened villi and reduced the villus-to-crypt ratio, whereas RES partially reinstated ileal morphology, decreased MDA dose-dependently and linearly enhanced duodenal SOD activity (p < 0.05). DEX downregulated Occludin mRNA; RES upregulated Occludin and elevated ileal GPX2, SOD, CAT and PPAR-γ transcripts with a quadratic response to RES dose, while lowering duodenal CAT mRNA. Overall, short-term RES supplementation—particularly at 1000–2000 mg/kg—improves growth performance, meat quality and intestinal health of yellow-feathered broilers under DEX-induced oxidative stress by enhancing systemic and intestinal antioxidant capacity and reinforcing epithelial barrier integrity. Full article

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

► Show Figures

Figure 1

16 pages, 981 KB

Open AccessArticle

The Natural Disinfectant Role of Essential Oils in Improving Radical Scavenging Activity and Total Phenolic Compounds in Fresh Vegetables

by Ben Allal Hafsa, Quesada-Granados José Javier, Agil Ahmad and Villalón-Mir Marina

Antioxidants 2025, 14(12), 1458; https://doi.org/10.3390/antiox14121458 - 5 Dec 2025

Abstract

The objective of this study was to evaluate the radical scavenging activity (RSA) and total polyphenolic content (TPC) in petiolate vegetables (baby spinach) and sessile vegetables (Romaine lettuce) disinfected with essential oils of thyme and peppermint compared with bleach solutions, a [...] Read more.

The objective of this study was to evaluate the radical scavenging activity (RSA) and total polyphenolic content (TPC) in petiolate vegetables (baby spinach) and sessile vegetables (Romaine lettuce) disinfected with essential oils of thyme and peppermint compared with bleach solutions, a chemical disinfectant widely used in food preparation. The vegetables, obtained from local markets in Granada (Spain), were treated with varying concentrations of essential oils and bleach solutions. Antiradical activity was evaluated using the DPPH radical scavenging method, while total polyphenols were determined using the Folin–Ciocalteu reagent. The results showed that essential oils significantly reduced microbial load, with inverse correlations between radical scavenging activity and microbial load and total phenolic compounds. Bleach solutions, on the other hand, show a strong direct correlation, significantly reducing the microbial load as well as the antiradical activity and total phenolic content. However, this antimicrobial and antioxidant effect depends on the morphological characteristics of the vegetable (stemmed or sessile) and the chemical composition of the essential oil. These results suggest that essential oils may be effective natural alternatives for disinfecting vegetables, as they increase their antiradical activity and polyphenolic content, in contrast to sodium hypochlorite, which affects the functional properties of the product by reducing the RSA and TPC. Full article

(This article belongs to the Special Issue Plants and Plant-Based By-Products as Valuable Sources of Antioxidants: Current Tendencies and Achievements in Their Exploitation)

► Show Figures

Figure 1

15 pages, 1573 KB

Open AccessArticle

The Effect of Newly Designed High-Antioxidant Food Products on Oxidative Stress and Antioxidant Markers in Athletes

by Kinga Zujko-Kowalska, Magdalena Stefanek, Izabela Łuszczewska, Łukasz Małek, Karol Adam Kamiński and Małgorzata Elżbieta Zujko

Antioxidants 2025, 14(12), 1457; https://doi.org/10.3390/antiox14121457 - 4 Dec 2025

Abstract

The aim of this study was to develop functional food with high antioxidant potential and to examine its effect on oxidative–antioxidant markers in the blood of athletes in an intervention study. The study population consisted of 40 athletes—long-distance runners who were divided into [...] Read more.

The aim of this study was to develop functional food with high antioxidant potential and to examine its effect on oxidative–antioxidant markers in the blood of athletes in an intervention study. The study population consisted of 40 athletes—long-distance runners who were divided into a study group (SG) and a control group (CG). Before and after the dietary intervention in the blood, the following were determined: total antioxidant status (TAS), antioxidant enzymes (superoxide dismutase—SOD, glutathione peroxidase—GPx, catalase—CAT) and total oxidative stress (TOS). Additionally, the oxidative stress index (OSI) was calculated. It was shown that in the SG after the dietary intervention, the TOS (p < 0.001) and OSI (p = 0.029) decreased, while the TAS increased (p < 0.001). However, no significant differences were found in the level of antioxidant enzymes in the SG. In the CG, dietary intervention did not affect the level of the assessed parameters. This study demonstrated that functional food in the form of a bar with high antioxidant potential, rich in polyphenols, dietary fiber, vitamin E, selenium, and magnesium, can support the body’s endogenous antioxidant system and restore oxidative–antioxidant homeostasis in athletes. However, further studies are needed, including a larger group of athletes, longer intervention times, and different periods of the annual training cycle. Full article

(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Components of the Diet)

► Show Figures

Figure 1

19 pages, 4447 KB

Open AccessArticle

Mechanism of Growth Phase-Dependent Nanoplastic Bioaccumulation in Tetrahymena thermophila

by Zhongquan Jiang, Tianyi Wei, Haipeng Tong, Ruikai Xing, Di Peng, Tao Yuan, Ling Zhao, Minghua Min and Wenbo Guo

Antioxidants 2025, 14(12), 1456; https://doi.org/10.3390/antiox14121456 - 4 Dec 2025

Abstract

Nanoplastics are ubiquitous in aquatic environments, and elucidating their bioaccumulation behavior is essential for assessing toxicity and trophic transfer risks. While most studies focus on nanoplastics properties (e.g., type, size, surface charge), the influence of organismal growth stage remains unclear. Through bioaccumulation kinetic [...] Read more.

Nanoplastics are ubiquitous in aquatic environments, and elucidating their bioaccumulation behavior is essential for assessing toxicity and trophic transfer risks. While most studies focus on nanoplastics properties (e.g., type, size, surface charge), the influence of organismal growth stage remains unclear. Through bioaccumulation kinetic experiments with 10 mg/L polystyrene nanoplastics (PSNPs), this study found that Tetrahymena thermophila (T. thermophila) in the lag phase (cell density 4 × 10⁴ cells/mL) exhibited the highest uptake rate of nanoplastics, 1.2–5.8 times that of the exponential phase (1–5 × 10⁵ cells/mL) and 7.7 times that of the stationary phase (>5 × 10⁵ cells/mL). Lag phase cells also had a larger specific surface area (0.319 vs. 0.271/0.269 μm⁻¹), supporting their heightened uptake capacity. Under PSNP exposure, exponential and stationary phase cells showed significantly elevated reactive oxygen species (ROS) levels, accompanied by downregulated superoxide dismutase (SOD) and stable catalase (CAT) activity, indicating impaired antioxidant defense and potential redirection of energy toward stress mitigation. Consistent with efficient internalization, confocal imaging revealed clear PSNP colocalization within food vacuoles of lag period cells. Proteomic and transcriptomic analysis further confirmed the upregulation of carrier proteins, FAD/FMN oxidoreductases, and pathways associated with cellular components (membrane and organelle membrane) and molecular functions (transporter activity and transmembrane transporter activity) in lag-phase T. thermophila. Collectively, these findings provide a molecular-level understanding of the multi-phase-dependent bioaccumulation of PSNPs, offering critical insights for assessing the environmental risks of polystyrene nanoplastics in dynamic aquatic ecosystems. Full article

► Show Figures

Figure 1

31 pages, 2381 KB

Open AccessReview

Roles of ROS and NO in Plant Responses to Individual and Combined Salt Stress and Waterlogging

by Taufika Islam Anee, Nasser A. Sewelam, Nonnatus S. Bautista, Takashi Hirayama and Nobuhiro Suzuki

Antioxidants 2025, 14(12), 1455; https://doi.org/10.3390/antiox14121455 - 3 Dec 2025

Abstract

During the climate change era, plants are increasingly exposed to multiple environmental challenges occurring simultaneously or sequentially. Among these, salt stress and waterlogging are two major factors that severely constrain crop productivity worldwide and often occur together. To survive under such conditions, plants [...] Read more.

During the climate change era, plants are increasingly exposed to multiple environmental challenges occurring simultaneously or sequentially. Among these, salt stress and waterlogging are two major factors that severely constrain crop productivity worldwide and often occur together. To survive under such conditions, plants have evolved sophisticated systems to scavenge harmful levels of reactive oxygen species (ROS). Despite their cytotoxic potential, ROS also act as key signaling molecules that interact with nitric oxide (NO), Ca²⁺, protein kinases, ion homeostasis pathways, and plant hormones. These signaling and acclimatory mechanisms are closely associated with the functions of energy-regulating organelles—chloroplasts and mitochondria—which are major sources of ROS under both individual and combined stresses. While many of these responses are shared between salt stress, waterlogging and their combination, it is likely that specific signaling mechanisms are uniquely activated when both stresses occur together—mechanisms that cannot be inferred from responses to each stress alone. Such specificity may depend on precise coordination among organelle-derived signals and the tight regulation of their cross-communication. Within this network, ROS and NO likely serve as central hubs, fine-tuning the integration of multiple signaling pathways that enable plants to adapt to complex and fluctuating stress environments. Full article

(This article belongs to the Special Issue Reactive Oxygen and Nitrogen Species in Plants―2nd Edition)

► Show Figures

Figure 1

17 pages, 1290 KB

Open AccessArticle

Selective Head Cooling and NOX Inhibition Protect the Blood–Brain Barrier in Neonatal Epilepsy

by Helena Parfenova, Jianxiong Liu, Shyamali Basuroy, Rong Zhang, Mimily Harsono and Massroor Pourcyrous

Antioxidants 2025, 14(12), 1454; https://doi.org/10.3390/antiox14121454 - 3 Dec 2025

Abstract

Epileptic seizures in the neonatal brain induce oxidative stress and disrupt the blood–brain barrier (BBB), leading to long-term cerebrovascular and neurodevelopmental deficits. This study examined the protective effects of selective head cooling and NADPH oxidase (NOX) inhibition on BBB integrity following seizures. Neonatal [...] Read more.

Epileptic seizures in the neonatal brain induce oxidative stress and disrupt the blood–brain barrier (BBB), leading to long-term cerebrovascular and neurodevelopmental deficits. This study examined the protective effects of selective head cooling and NADPH oxidase (NOX) inhibition on BBB integrity following seizures. Neonatal seizures were induced in newborn pigs with bicuculline under normothermic or selective head cooling conditions. BBB disruption was assessed by Evans Blue extravasation and quantification of circulating brain-derived endothelial cells (CD45⁻/CD146⁺/GluT1⁺). Seizures under normothermia caused marked BBB leakage, cerebrovascular apoptosis, and elevated endothelial biomarkers, whereas selective head cooling (cortical temperature ~25 °C, body ~35 °C) significantly reduced these effects. Pharmacological inhibition of NOX with setanaxib (5 mg/kg) or sulforaphane (0.4 mg/kg) also prevented BBB disruption during normothermia. In vitro, primary porcine and human brain endothelial cells exposed to glutamate or TNF-α showed increased NOX activity, ROS production, apoptosis, and barrier leakage, all attenuated by NOX inhibitors or moderate hypothermia (<30 °C). These findings identify endothelial NOX as a key mediator of seizure-induced BBB injury and demonstrate that both NOX inhibition and selective head cooling effectively preserve cerebrovascular integrity. Combined hypothermic and antioxidant therapy may offer a promising strategy to prevent cerebrovascular injury and BBB damage in neonatal epilepsy. Full article

(This article belongs to the Special Issue Roles of NADPH Oxidase in Modulation of Signal Transduction and Cellular Metabolism—2nd Edition)

► Show Figures

Figure 1

29 pages, 12598 KB

Open AccessArticle

Cuban Sugarcane Wax Alcohol Supplementation Prevents Brain and Eye Damages of Zebrafish Exposed to High-Cholesterol and High-Galactose Diet for 30 Weeks: Protection of Myelin, Cornea, and Retina

by Kyung-Hyun Cho, Ashutosh Bahuguna, Cheolmin Jeon, Sang Hyuk Lee, Yunki Lee, Seung Hee Baek, Chae-Eun Yang, Ji-Eun Kim and Krismala Djayanti

Antioxidants 2025, 14(12), 1453; https://doi.org/10.3390/antiox14121453 - 3 Dec 2025

Abstract

Cuban sugarcane wax alcohol (policosanol) is a blend of eight characteristic aliphatic alcohols extracted from the Cuban sugarcane and widely recognized for its multifunctional applications and therapeutic properties. In the present study, the potency of policosanol (POL) was assessed for its ability to [...] Read more.

Cuban sugarcane wax alcohol (policosanol) is a blend of eight characteristic aliphatic alcohols extracted from the Cuban sugarcane and widely recognized for its multifunctional applications and therapeutic properties. In the present study, the potency of policosanol (POL) was assessed for its ability to prevent metabolic stress and associated disorders posed by a high-cholesterol (HC) and high-galactose (HG) diet in zebrafish (Danio rerio). Adult zebrafish (n = 56/group) were fed either with an HC+HG diet (containing 4%, w/w cholesterol and 30%, w/w galactose), or an HC+HG amalgamated diet with POL (final 0.1% w/w or 0.5% w/w). Zebrafish in the specified groups were sacrificed post-30 weeks of feeding, and blood and organs (liver, brain, and eyes) were processed for biochemical, histological, and immunohistochemical (IHC) analysis. After 30 weeks of feeding, the highest mortality (12.5%) was noticed in the HC+HG supplement group, which was reduced to 4.5% with co-supplementation of POL (0.1% and 0.5%). In a dose-dependent manner, POL significantly reversed HC+HG elevated levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), glucose, and malondialdehyde (MDA), while substantially augmenting plasma high-density lipoprotein cholesterol (HDL-C), sulfhydryl content, ferric ion reduction ability (FRA), and paraoxonase (PON) activity. In addition, POL mitigated HC+HG-induced hepatomegaly, inflammation, and fatty liver changes. Consistently, POL minimizes ROS generation and cellular senescence in the brain and substantially improves HC+HG-induced cognitive changes (cessation of swimming ability and motion), with a marked ~5 times higher swimming distance. Notably, POL mitigated the HC+HG-induced corneal opacity and attenuated oxidative stress, apoptosis, 4-hydroxynonenal (4-HNE) accumulation, and myelin sheath degeneration in the retina. The findings underscore the therapeutic potential of policosanol in attenuating oxidative stress, metabolic changes, and various organ damage caused by prolonged exposure to the HC+HG diet. Full article

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

► Show Figures

Figure 1

21 pages, 2406 KB

Open AccessArticle

Lactarius deliciosus Extract from Green Microwave-Assisted Eutectic Solvent Extraction as a Therapeutic Candidate Against Colon Cancer

by Seyed Hesamoddin Bidooki, Beatriz Rodríguez-Martínez, Javier Quero, Luis Vicente Herrera-Marcos, Mónica Paesa, Marina Delgado-Machuca, Oscar F. Beas-Guzmán, Jesús Osada, Pedro Ferreira-Santos and María Jesús Rodríguez-Yoldi

Antioxidants 2025, 14(12), 1452; https://doi.org/10.3390/antiox14121452 - 2 Dec 2025

Abstract

Lactarius deliciosus is a widely distributed edible mushroom valued as a functional food due to its rich content of nutrients, phenolic compounds, and flavonoids, which contribute to its strong antioxidant and antimicrobial properties. The present study aimed to optimize a green microwave-assisted extraction [...] Read more.

Lactarius deliciosus is a widely distributed edible mushroom valued as a functional food due to its rich content of nutrients, phenolic compounds, and flavonoids, which contribute to its strong antioxidant and antimicrobial properties. The present study aimed to optimize a green microwave-assisted extraction method for maximal recovery of bioactive phenolic compounds from Lactarius deliciosus extract (LDE) and to evaluate its antioxidant, antiproliferative, antimetastatic, and anti-inflammatory effects on human colon carcinoma (Caco-2) cells. The study demonstrated that solvent polarity and composition critically influence the recovery of antioxidant biomolecules, identifying water and NaDES 1 (glycerol/glycine/water) as the most efficient and sustainable solvents for microwave-assisted extraction at 225 °C. The LDE showed high levels of phenolic compounds—particularly 4-hydroxybenzoic and vanillic acids—indicating potent antioxidant potential and possible anticancer efficacy. The results revealed that the LDE significantly reduced colony formation and cell adhesion in a dose-dependent manner, leading to nearly complete inhibition of clonogenic survival at the IC₅₀ concentration and a marked increase in cell death among non-adherent colon cancer cells. In addition, LDE inhibited the proliferation of Caco-2 cells by inducing G0/G1 cell cycle arrest and apoptosis, associated with altered mitochondrial potential and increased caspase-3 activity. The LDE modified the redox balance of the cell by decreasing the ROS levels and exerts anti-inflammatory effects through significant downregulation of NOS2 expression, without adversely affecting the intestinal barrier. The study concludes that LDE bioactive compounds show strong promise as anticancer and functional ingredients, demonstrating antioxidant, antiproliferative, antimetastatic, and anti-inflammatory effects. Full article

(This article belongs to the Special Issue Phenolic Profiling and Antioxidant Capacity of Natural Products)

► Show Figures

Graphical abstract

22 pages, 2030 KB

Open AccessArticle

Synergistic Genotoxic Effects of Gamma Rays and UVB Radiation on Human Blood

by Angeliki Gkikoudi, Athanasia Adamopoulou, Despoina Diamadaki, Panagiotis Matsades, Ioannis Tzakakos, Sotiria Triantopoulou, Spyridon N. Vasilopoulos, Gina Manda, Georgia I. Terzoudi and Alexandros G. Georgakilas

Antioxidants 2025, 14(12), 1451; https://doi.org/10.3390/antiox14121451 - 2 Dec 2025

Abstract

Exposure to ionizing and non-ionizing radiation from environmental and clinical settings can significantly threaten genomic stability, especially when combined. This ex vivo study investigates the potential combined effects of gamma radiation and ultraviolet B (UVB) exposure on human peripheral blood mononuclear cells (PBMCs) [...] Read more.

Exposure to ionizing and non-ionizing radiation from environmental and clinical settings can significantly threaten genomic stability, especially when combined. This ex vivo study investigates the potential combined effects of gamma radiation and ultraviolet B (UVB) exposure on human peripheral blood mononuclear cells (PBMCs) from healthy donors by exposing whole blood and isolated PBMCs to 1 Gy of gamma rays, to an absolute dose of approximately 100 J/m² of UVB, or to their combination. Combined exposure resulted in significantly elevated γH2AX foci formation and chromosomal aberrations relative to individual stressors, with the most pronounced effects observed in isolated PBMCs. Notably, lymphocytes from some donors failed to proliferate after UVB or co-exposure. Based on our results, a predictive biophysical model derived from dicentric yield was developed to estimate the gamma-ray equivalent dose from co-exposure, indicating up to ~9% increase in lifetime cancer risk. Although this proof-of-concept study included only a small number of donors and focused on two endpoints (γH2AX and dicentric assays), it provides a controlled framework for investigating mechanisms of radiation-induced genomic instability. The results emphasize the importance of accounting for mixed radiation exposures in genotoxic risk assessment and radiation protection. Full article

(This article belongs to the Special Issue Radiation Exposure and Health: The Role of Oxidative Stress and Inflammatory Response)

► Show Figures

Figure 1

20 pages, 5021 KB

Open AccessArticle

Protective Effects of Natural Lipophilic Antioxidants on UV-Induced Lipid Oxidation in Liposomes and Their Enhancement

by Anna Heidrich, Melvin Höfer and Volker Böhm

Antioxidants 2025, 14(12), 1450; https://doi.org/10.3390/antiox14121450 - 2 Dec 2025

Abstract

Antioxidants, especially lipophilic antioxidants, absorb ultraviolet (UV) radiation and protect human skin from radicals that lead to oxidation reactions. The differences in the protective effects of carotenoids and α-tocopherol against UV radiation and the possible enhanced effects by the polar antioxidants, vitamin C [...] Read more.

Antioxidants, especially lipophilic antioxidants, absorb ultraviolet (UV) radiation and protect human skin from radicals that lead to oxidation reactions. The differences in the protective effects of carotenoids and α-tocopherol against UV radiation and the possible enhanced effects by the polar antioxidants, vitamin C and Trolox, need further investigation. Therefore, malondialdehyde was analyzed as a biomarker for lipid oxidation using the Thiobarbituric Acid-Assay (TBA-Assay) in liposomes irradiated with UV-C, UV-B, and UV-A radiation (254 nm, 320 nm, and 360 nm). In addition, antioxidant degradation was analyzed using HPLC with a diode array or fluorescence detector. The lipophilic antioxidants differ in their effect mainly due to their polarity and the associated different localization in the lipid bilayer. No pro-oxidative effect was observed at antioxidant concentrations close to saturation. The antioxidant effect was low at small concentrations, mainly due to aggregation of the antioxidants. The protective effect at higher antioxidant concentrations increased from up to 25–72% under UV-C, over 59–77% under UV-B, to 77–86% under UV-A radiation. Vitamin C proved to be 2–40 times less effective depending on the wavelength and the lipophilic antioxidant. Mixtures of lipophilic and hydrophilic antioxidants showed partially additive or synergistic effects. This appears to be dependent on concentration and ratio. Full article

(This article belongs to the Special Issue Hydrophilic and Lipophilic Antioxidants in Foods and Food Processing)

► Show Figures

Figure 1

19 pages, 2775 KB

Open AccessArticle

Cuspidatyl Ferulate, a Novel Phenolic Acid from Hyssopus cuspidatus Borris, Protects Hepatocytes Against Oxidative Damage via Keap1 Interaction

by Xingyu Liu, Zhao Zhang, Denghui Gao, Xiaoguang Yang, Lei Liu, Guannan Wang, Zhenbo Song, Weiwei Fang and Shuyue Wang

Antioxidants 2025, 14(12), 1449; https://doi.org/10.3390/antiox14121449 - 1 Dec 2025

Abstract

Lipotoxicity and oxidative stress are key pathogenic drivers in the development of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The underlying mechanisms of MASLD are not fully understood, and approved pharmacotherapies remain elusive. Thus, exploring therapeutic targets and potential drugs for MASLD is still [...] Read more.

Lipotoxicity and oxidative stress are key pathogenic drivers in the development of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The underlying mechanisms of MASLD are not fully understood, and approved pharmacotherapies remain elusive. Thus, exploring therapeutic targets and potential drugs for MASLD is still a major challenge. In our previous study, a new cuspidatyl ferulate (2,3-dihydroxy-4-carboxylic butyl (E)-4-[3-(4-hydroxy-3-methoxyphenyl)-2-propenoate], CuF) was first isolated and identified from Hyssopus cuspidatus Boriss (H. cuspidatus). Here, we investigated the effects of this novel phenolic acid on free fatty acid (FFA)-induced oxidative stress and lipid accumulation in HepG2 cells. Exposure to FFA significantly increased intracellular reactive oxygen species (ROS) levels and lipid accumulation. Notably, CuF treatment effectively reversed FFA-induced suppression of key antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT), and attenuated lipid accumulation, as evidenced by reduced total cholesterol (TC) and triglyceride (TG) levels. Mechanistically, molecular docking and capillary electrophoresis analyses revealed that CuF directly interacts with Kelch-like ECH-associated protein 1 (Keap1), disrupting the Keap1-Nrf2 protein complex, thereby promoting nuclear translocation of Nrf2 and activating the antioxidant response pathway. In summary, our findings demonstrate that this novel phenolic acid exhibits strong antioxidant and anti-lipotoxic activities in vitro, offering a potential natural product-based drug candidate for MASLD therapy. Full article

(This article belongs to the Collection Advances in Antioxidant Ingredients from Natural Products)

► Show Figures

Figure 1

18 pages, 4065 KB

Open AccessArticle

Physiological Responses of Tomato Plants with Varied Susceptibility to Multiple Drought Stress

by Hong Chen, Yi Liu, Fei Ding, Yankai Li, Carl-Otto Ottosen, Xiaoming Song, Fangling Jiang, Zhen Wu, Xiaqing Yu and Rong Zhou

Antioxidants 2025, 14(12), 1448; https://doi.org/10.3390/antiox14121448 - 1 Dec 2025

Abstract

Frequent extreme weather events exacerbate agricultural abiotic stress, with drought causing widespread yield loss. Tomato, a globally important vegetable sensitive to water deficit, has been predominantly studied under single-drought scenarios that poorly reflect recurrent field conditions. This study investigated physiological and molecular responses [...] Read more.

Frequent extreme weather events exacerbate agricultural abiotic stress, with drought causing widespread yield loss. Tomato, a globally important vegetable sensitive to water deficit, has been predominantly studied under single-drought scenarios that poorly reflect recurrent field conditions. This study investigated physiological and molecular responses of two tomato genotypes to repeated drought stress. Results showed that the drought-sensitive genotype ‘TGTB’ exhibited faster ABA accumulation and more pronounced ABA-mediated stomatal closure. During the second drought cycle, stomatal pore length and width were significantly smaller than during the first drought, indicating a strong stress memory effect. In contrast, the drought-tolerant ‘LA1598’ showed minimal memory responses. Under extreme drought stress, primed and non-primed ‘TGTB’ plants showed significantly lower H₂O₂ content than controls, whereas primed ‘LA1598’ plants maintained a significantly lower O₂^·− production rate than non-primed plants during both extreme drought cycles. Antioxidant enzyme systems contributed to ROS homeostasis, supported by the regulation of key drought-responsive genes. This study demonstrates genotype-dependent memory capacity and reveals that drought priming enhances repeated drought tolerance through ABA-regulated stomatal adjustment. These findings provide a theoretical basis for improving tomato resilience to recurrent drought and supporting breeding of drought-tolerant varieties. Full article

(This article belongs to the Special Issue Antioxidant Defense in Mitigating Abiotic Stresses in Plants: Mechanisms, Innovations, and Applications)

► Show Figures

Figure 1

22 pages, 1299 KB

Open AccessArticle

Polyphenol Powders from Ginkgo biloba L. and Clitoria ternatea L.: Influence of Drying Techniques and Carriers on Antioxidant Capacity and Polyphenol Release Profiles

by Alicja Kucharska-Guzik, Jessica Brzezowska, Klaudia Masztalerz, Mariusz Nejman, Łukasz Guzik and Anna Michalska-Ciechanowska

Antioxidants 2025, 14(12), 1447; https://doi.org/10.3390/antiox14121447 - 1 Dec 2025

Abstract

This study evaluated the impact of the drying and carrier type on the physicochemical and functional properties of Ginkgo biloba L. and Clitoria ternatea L. extracts and their blends, at ratios of 1:1, 1:2, and 2:1 (w/w). Extracts were [...] Read more.

This study evaluated the impact of the drying and carrier type on the physicochemical and functional properties of Ginkgo biloba L. and Clitoria ternatea L. extracts and their blends, at ratios of 1:1, 1:2, and 2:1 (w/w). Extracts were obtained using water as a green solvent and dried by freeze− or spray drying with maltodextrin or inulin. Powders were characterized for moisture content, water activity, color, polyphenol composition (HPLC–MS/MS), and antioxidant capacity (Folin–Ciocalteu, TEAC ABTS, FRAP). Spray−dried samples exhibited lower moisture content and water activity, while freeze-drying ensured higher polyphenol levels. The 1:1 (w/w) blend with inulin showed the most favorable balance between stability and antioxidant capacity, indicating synergistic effects. This formulation was selected for pilot-scale processing and encapsulated into hard gelatin capsules, which demonstrated rapid polyphenols release under simulated gastric conditions. The findings highlight the potential of spray-dried polyphenol-rich powders as standardized ingredients for immediate-release dietary supplements. Full article

(This article belongs to the Special Issue Natural Antioxidants from Plant-Based By-Products: Mechanisms and Applications in Food Systems)

► Show Figures

Graphical abstract

19 pages, 1462 KB

Open AccessArticle

Effects of Food Enrichment Based on Diverse Feeding Regimes on Growth, Immunity, and Stress Resistance of Nibea albiflora

by Yuhan Ruan, Jipeng Sun, Yuting Zheng, Jiaxing Wang, Dongdong Xu, Tianxiang Gao, Anle Xu and Xiumei Zhang

Antioxidants 2025, 14(12), 1446; https://doi.org/10.3390/antiox14121446 - 30 Nov 2025

Abstract

Food enrichment represents a novel feeding strategy for aquaculture. In the current study, juvenile Nibea albiflora (average weight 29.65 ± 0.13 g) were used and three feeding regimes (A—commercial diet; B—a diet comprising 90% commercial feed and 10% ice-fresh Palaemon gravieri; C—a [...] Read more.

Food enrichment represents a novel feeding strategy for aquaculture. In the current study, juvenile Nibea albiflora (average weight 29.65 ± 0.13 g) were used and three feeding regimes (A—commercial diet; B—a diet comprising 90% commercial feed and 10% ice-fresh Palaemon gravieri; C—a diet consisting of 90% commercial diet, 5% ice-fresh Palaemon gravieri and 5% live Perinereis nuntia; named control group, Group 1, and Group 2) with comparable nutrient compositions: were designed to establish the food enrichment model and explore the effects of such feeding strategies on the fish. The cultivation period was 60 days, and the physiological, pathological, and RNA-seq analyses were performed to evaluate the effects. The results showed that the food enrichment feeding strategy significantly enhanced fish growth performance, immunity, and stress resistance without increasing the unit production cost (UPC). Furthermore, the tri-combined food feeding (C) was better than the two-combined food feeding (B). Liver transcriptomic analysis revealed that, in the comparison between the control group and Group 1, the up-regulated genes (alox15b, gng7, hif1a, ppara, and pla2g) and down-regulated genes (ins, gck, il4i1) influenced fish physiology and further improved growth. Similar to the comparison between the control group and Group 2, the major functional genes included ugt, nlrp3, mx1, col1a, gst (up-regulated), and map2k1, myc, mmp9, wnt7, socs3 (down-regulated) that participated in regulating the body growth, immunity, and stress resistance. The up-regulated genes (ins, mhc2, foxo3, ppara, and mx1) alongside the down-regulated genes (egfr, fos, cyc, myc, and mmp9) probably contributed to the enhanced efficacy of the tri-combined food feeding compared to the two-combined food feeding. In summary, this study demonstrates the beneficial effects of such a food enrichment model on the fish and provides empirical evidence supporting the implementation of the feeding strategies in the healthy culturing of the fish. Full article

► Show Figures

Figure 1

6 pages, 173 KB

Open AccessEditorial

Antioxidant Response in Skeletal Muscle

by Elżbieta Supruniuk and Jan Górski

Antioxidants 2025, 14(12), 1445; https://doi.org/10.3390/antiox14121445 - 30 Nov 2025

Abstract

Skeletal muscle, which in men accounts for nearly half of the body’s mass, stands out as the most adaptable and energetically demanding tissue [...] Full article

(This article belongs to the Special Issue Antioxidant Response in Skeletal Muscle)

Journal Description

Antioxidants

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI