Search Results (390)

Pregnancy represents a period of heightened oxidative demand in which maternal metabolic adaptations are tightly regulated by redox-sensitive molecular pathways. Imbalances in these systems have been associated with gestational complications, impaired placental function, and long-term effects on offspring health. This review examines the molecular mechanisms through which adherence to the Mediterranean diet (MD) influences oxidative balance during pregnancy. We summarize evidence on how MD-derived bioactives regulate oxidative stress pathways and affect oxidative stress biomarkers, as well as the expression of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. At the same time, certain MD foods containing environmental contaminants may potentially attenuate its protective effects. In addition, the review explores molecular insights into how the MD may counteract oxidative stress induced by environmental pollutants through modulation of redox signaling and detoxification pathways. By integrating biochemical, molecular, and environmental perspectives, this review highlights the MD as a potential nutrigenomic intervention to optimize oxidative balance, support healthy pregnancy outcomes linked to environmental pollution. Full article

Nanotechnology has emerged as a transformative tool in animal production, offering novel strategies to enhance productivity, health, and product quality. Among trace elements, selenium (Se) plays an essential role in antioxidant defence, immune regulation, and redox balance through its incorporation into selenoproteins. Selenium nanoparticles (SeNPs), synthesized via chemical, physical, or biological methods, have shown superior bioavailability, stability, and lower toxicity compared to traditional organic and inorganic selenium forms. This review explores the synthesis, physicochemical properties, and metabolic fate of SeNPs, emphasizing their advantages in poultry production systems. In poultry, SeNPs exhibit potent antioxidant and anti-stress effects by enhancing the activity of glutathione peroxidase, superoxide dismutase, and thioredoxin reductase, thereby mitigating lipid peroxidation and oxidative tissue damage. Their immunomodulatory effects are linked to improved lymphocyte proliferation, cytokine regulation, and increased immunoglobulin levels under normal and stress conditions. SeNP supplementation has been associated with enhanced growth performance, feed efficiency, carcass quality, and reproductive outcomes in broilers, layers, and quails. Furthermore, selenium nanoparticles have demonstrated therapeutic potential in preventing or alleviating chronic diseases such as cancer, diabetes, cardiovascular dysfunction, and neurodegenerative disorders. SeNPs also serve as biofortification agents, increasing selenium deposition in poultry meat and eggs, thus improving their nutritional value for human consumption. However, selenium’s narrow safety margin requires careful dose optimization to avoid potential toxicity. This review highlights the multifaceted benefits of selenium nanoparticles in poultry nutrition and health, while underscoring the need for further studies on grey SeNPs, long-term safety, and regulatory frameworks. Integrating SeNPs into poultry production represents a promising strategy to bridge animal health, food security, and public nutrition. Full article

Background/Objectives: The global prevalence and incidence of inflammatory bowel diseases have risen in the past two decades. Among them, Crohn’s disease and ulcerative colitis are still challenging to treat due to vascular and proliferative alterations. Studies in rats suggest that blocking histamine receptors (H1–H4) can improve colitis progression. However, the specific histamine receptor responsible for this effect remains debated. The experiment aimed to assess the role of specific histamine receptor subtypes in colitis development, focusing on oxidative stress markers in the liver and skeletal muscle. Methods: The study involved 60 adult male Wistar rats, divided into control and colitis experimental groups. Colitis was induced through intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid. Animals in both experimental groups received intramuscular injections of NaCl (non-treated, NT) or H1, H2, H3, and H4 receptor antagonists (10 study subgroups in total). On day eight, the animals were re-anesthetized and euthanized via exsanguination. Then, liver and skeletal muscle (m. soleus) samples were collected for analysis of oxidative stress markers. Results: The analyses of skeletal muscle samples showed that using the H1 and H2 receptor antagonists increased superoxide dismutase (SOD) and catalase (CAT) activities, as well as parameters related to glutathione metabolism (reduced glutathione (GSH), glutathione S-transferase (GST)) in rats from the control groups, indicating enhanced antioxidant defense. In rats with chemically induced colitis, we observed that H1 receptor antagonists elevated CAT activity, whereas β-esterase (β-EST) activity remained elevated across all colitis subgroups. In the liver, histamine receptor antagonists produced receptor-specific redox effects: the H2 receptor antagonist reduced oxidative damage (malondialdehyde (MDA)); the H1 receptor antagonist attenuated SOD hyperactivity, but depleted GSH; and the H4 receptor antagonist increased GSH while elevating MDA. Chemically induced colitis increased α- and β-EST activities, whereas administration of the H1 or H3 antagonist reduced β-EST levels. Conclusions: Histamine receptor antagonists modulated oxidative stress responses in both liver and skeletal muscle tissues in a receptor-dependent manner. Among them, the H2 receptor antagonist most effectively mitigated hepatic oxidative injury, highlighting its potential as a therapeutic target in colitis-associated systemic oxidative stress. Full article

Ischemic stroke is a major cause of long-term disability and death, with oxidative stress contributing substantially to post-ischemic injury. Reperfusion restores oxygen supply but simultaneously increases reactive oxygen species (ROS), amplifying secondary neuronal damage. This study examined time-dependent changes in systemic thiol redox status following transient middle cerebral artery occlusion (tMCAO) in rats. Plasma concentrations of cysteine (CySH), cystine (CySS), glutathione (GSH), and glutathione disulfide (GSSG), along with corresponding CySS/CySH and GSSG/GSH ratios and redox potentials (Eh), were evaluated 24 and 48 h after occlusion. At 24 h, thiol concentrations and redox ratios showed no significant differences between sham and tMCAO groups. By 48 h, a marked oxidative shift emerged, characterized by reduced CySH, elevated GSSG, and significant increases in both CySS/CySH and GSSG/GSH ratios. Redox potentials also demonstrated substantial oxidation at this time point. These findings indicate that prolonged ischemia–reperfusion induces systemic oxidative stress, with plasma redox status serving as a sensitive indicator of reperfusion-related injury. The results underscore the plasma redox status as a potentially sensitive biomarker of reperfusion-induced oxidative injury and support the therapeutic value of targeting redox imbalance to mitigate oxidative damage following stroke. Full article

Landfills represent increasingly common anthropogenic habitats that provide food resources but also expose wildlife to complex chemical mixtures. White Storks (Ciconia ciconia) have recently expanded breeding near such sites, yet little is known about the physiological consequences of landfill dependence across time. In 2025, we assessed biomarker responses in White Stork (Ciconia ciconia) nestlings from the Jakuševec landfill (Zagreb, Croatia), a post-remediated site still in partial operation, three years after the initial studies conducted in 2021 and 2022. Activities of acetylcholinesterase (AChE), carboxylesterase (CES), glutathione S-transferase (GST) and glutathione reductase (GR), as well as levels of reduced glutathione (GSH) and reactive oxygen species (ROS), were quantified in extracellular (plasma) and intracellular (post-mitochondrial S9) blood fractions. Neurotoxicity biomarkers (AChE, CES) showed small increases in 2022, followed by significant declines in 2025, indicating potential changes in exposure to neuroactive compounds. Oxidative-stress biomarkers displayed contrasting patterns: GST and GR decreased progressively, whereas ROS rose and GSH shifted in opposite directions between fractions, together suggesting rising oxidative challenge and altered redox balance. The combined biomarker response suggests continuing low-level exposure to neurotoxic and redox-active compounds despite landfill remediation. Our findings highlight that urban landfills, even in post-closure phases, remain physiologically active systems influencing wildlife health and should be incorporated into long-term ecotoxicological and conservation monitoring frameworks. While independent long-term monitoring shows that the Jakuševec White Stork colony has continued to grow over the past decade, the physiological responses detected in nestlings highlight the importance of assessing how chronic low-level exposure might influence population health in the long term. Full article

Oxidative stress is a defining feature of stroke pathology, but the magnitude, timing and impact of redox imbalance are not static. Emerging evidence indicates that physiological contexts, such as aging, metabolic stress, and circadian disruption, continuously reshape oxidative status and determine the brain’s vulnerability to ischemic and reperfusion injury. This review integrates recent insights into how these intrinsic modulators govern the transition from adaptive physiological redox signaling to pathological oxidative stress during stroke. Aging compromises mitochondrial quality control and blunts NRF2-driven antioxidant responses, heightening susceptibility to ROS-driven damage. Metabolic dysfunction, as seen in obesity and diabetes, amplifies oxidative burden through NADPH oxidase activation, lipid peroxidation, and impaired glutathione recycling, further aggravating post-ischemic inflammation. Circadian misalignment, meanwhile, disrupts the rhythmic expression of antioxidant enzymes and metabolic regulators such as BMAL1, REV-ERBα, and SIRT1, constricting the brain’s temporal window of resilience. We highlight convergent signaling hubs, NRF2/KEAP1, SIRT–PGC1α, and AMPK pathways, as integrators of these physiological inputs that collectively calibrate redox homeostasis. Recognizing oxidative stress as a dynamic, context-dependent process reframes it from a static pathological state to a dynamic outcome of systemic and temporal imbalance, offering new opportunities for time-sensitive and metabolism-informed redox interventions in stroke. Full article

Micronutrient malnutrition persists as a global health burden, while conventional biofortification approaches suffer from low efficiency and environmental trade-offs. This study aimed to develop and evaluate a foliar-applied selenium–zinc nanocomposite (Nano-ZSe, a mixture of zinc ionic fertilizer and nano selenium) for synergistic Se/Zn co-biofortification in Brassica chinensis L., using a controlled pot experiment that integrated physiological, metabolic, molecular, and rhizosphere analyses. Application of Nano-ZSe at 0.18 mg·kg⁻¹ (Based on soil weight) not only increased shoot biomass by 28.4% but also elevated Se and Zn concentrations in edible tissues by 7.00- and 1.66-fold (within the safe limits established for human consumption), respectively, compared to the control. Mechanistically, Nano-ZSe reprogrammed the ascorbate-glutathione redox system and redirected carbon flux through the tricarboxylic acid cycle, suppressing acetyl-CoA biosynthesis and reducing abscisic acid accumulation. This metabolic rewiring promoted stomatal opening, thereby enhancing foliar nutrient uptake. Simultaneously, Nano-ZSe triggered the coordinated upregulation of BcSultr1;1 (a sulfate/selenium transporter) and BcZIP4 (a Zn²⁺ transporter), enabling synchronized translocation and the tissue-level co-accumulation of Se and Zn. Beyond plant physiology, Nano-ZSe improved soil physicochemical properties, enriched rhizosphere microbial diversity, and increased crop yield and economic returns. Collectively, this work demonstrates that nano-enabled dual-nutrient delivery systems can bridge nutritional and agronomic objectives through integrated physiological, molecular, and rhizosphere-mediated mechanisms, offering a scalable and environmentally sustainable pathway toward functional food production and the mitigation of hidden hunger. Full article

Metabolomics research in schizophrenia has revealed consistent alterations across multiple biochemical domains, including energy metabolism, lipid composition, amino acid pathways, and oxidative stress regulation. The most reproducible findings include the dysregulation of the tryptophan–kynurenine pathway, disturbances in arginine/nitric oxide metabolism, alterations in phospholipid and sphingolipid profiles, reduced glutathione (GSH) in the brain, and elevated lactate levels, suggesting mitochondrial dysfunction. Antipsychotic treatment itself modifies a wide range of metabolites, complicating biomarker discovery. Although no single biomarker has yet achieved clinical utility, systematic reviews and Mendelian randomization studies provide evidence for validated biomarker panels and potential causal links between peripheral metabolite signatures and schizophrenia risk. The aim of this study is to characterize metabolic changes in patients diagnosed with schizophrenia, where each group received different non-invasive therapeutic methods and was compared to patients continuing standard pharmacotherapy without modification. The study results show that schizophrenia is associated with systemic metabolic disturbances affecting energy, amino acid, lipid, and redox pathways. Further development of research in this area requires comprehensive and long-term studies integrated with modern imaging and analytical techniques. Full article

ARGONAUTE 1 (AGO1) selectively recruits microRNAs (miRNAs) and some small interfering RNAs (siRNAs) to form an RNA-induced silencing complex (RISC) to regulate gene expressions and also promotes the transcription of certain genes through direct chromatin binding. Complete dysfunction of AGO1 causes extremely serious growth arrest and sterility in Arabidopsis. Here, we characterize an ago1-38 allele with distinctive morphological abnormalities obviously distinguishing it from the other ago1 alleles, such as ago1-25 and ago1-45. The aberrant phenotypes of ago1-38 were completely restored in its transgenic complementation lines harboring an AGO1 promoter and coding sequence. To investigate the mechanism underlying the unique phenotype of ago1-38, integrated transcriptomic and metabolomic analysis was employed. The glutathione metabolism pathway was significantly co-enriched in the integrated analysis of ago1-38, suggesting an altered balance of the glutathione-related redox system. Transcriptomic analysis showed that many genes in the siRNA processing pathway were significantly changed in ago1-38, suggesting the dysregulation of the siRNA pathway. Meanwhile, numerous genes, particularly the large set of transcriptional factors associated with plant–pathogen interaction networks and phytohormone signaling cascades, exhibited altered expression patterns, implying perturbed immune defense and hormonal signaling. Collectively, these findings provide new insights into the multifaceted roles of AGO1 in siRNA processing, pathogen response, and phytohormone signaling. Full article

Oxidative stress (OS) is increasingly recognized as a dynamic disturbance of cellular redox networks rather than a simple imbalance between oxidants and antioxidants. In this context, ferroptosis and cuproptosis—two regulated and metal-dependent forms of cell death—emerge as key mechanisms linking OS to metabolic dysfunction, inflammation, and tissue injury. This review integrates findings from biochemical, lipidomic and metallomic studies to describe how lipid peroxidation (LPO), glutathione (GSH)–Glutathione Peroxidase 4 (GPX4) activity, ferritinophagy, copper-induced mitochondrial protein lipoylation, and altered communication between organelles generate distinct redox signatures across diseases. By examining cutaneous, metabolic, cardiovascular, infectious, neurodegenerative, and oncologic conditions, we outline the shared redox pathways that connect iron- and copper-dependent cell death to systemic inflammation, immune dysregulation, and chronic tissue damage. Common oxidative markers—such as oxidized phospholipids, lipid aldehydes including 4-Hydroxynonenal (4-HNE) and malondialdehyde (MDA), and systemic metal imbalance—are highlighted as potential indicators of disease severity and as emerging therapeutic targets. We also discuss innovative analytical tools, including redox lipidomics, metallomic profiling and artificial-intelligence (AI)-based classification approaches, which improve the characterization of redox vulnerability and may guide the development of precision redox therapies. Overall, ferroptosis and cuproptosis represent unifying mechanisms that connect OS to multisystem disease and provide new opportunities for diagnostic refinement and targeted antioxidant-based interventions. Full article

Background and Objectives: Oxidative stress plays a central role in numerous pathological and toxicological processes, and in vivo investigations are essential for understanding integrated systemic responses. Methylxanthines have been reported to modulate redox homeostasis through multiple mechanisms, but their effects in aquatic vertebrate models under metal nanoparticle-induced oxidative stress remain poorly characterized. Materials and Methods: In the present study, adult zebrafish were exposed for 15 days to ZnO nanoparticles (0.69 mg/L) as a pro-oxidant model, and to methylxanthines (caffeine, theobromine, theophylline; 50 mg/L). Oxidative stress biomarkers were assessed by measuring the levels of glutathione peroxidase 1 (GPx1), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) in whole-body homogenates using ELISA. Complementary molecular docking was performed to investigate methylxanthine–enzyme interactions. Results: The most substantial change was observed for SOD level, which significant increased compared to the control group (from 0.122 to 1.090 ng/g; p = 0.001), followed by CAT, which rose from 38.3 pg/g to 100.8 pg/g; p = 0.001), and GPX1 which increased from 84.3 pg/g to 142.2 pg/g; p = 0.011). In parallel, GSH levels decreased by 58.7% (p = 0.001). Co-exposure to methylxanthines significantly modulated the ZnO-NPs exposure response, by mitigating the increase in antioxidant enzyme levels and restoring glutathione. Among the tested compounds, theobromine exerted the strongest protective effect on GPx1 and GSH and caffeine primarily influenced CAT and SOD, whereas theophylline showed overall weaker responses. The molecular docking investigation indicated that all tested methylxanthines can attach to different cavities of the antioxidant enzymes. Theophylline and theobromine established hydrogen bonds and π-stacking interactions with the interfacing amino acids, potentially contributing to the modulation of enzymes stabilization and function under physiological conditions. Conclusions: ZnO-NPs trigger a robust systemic response in zebrafish, whereas methylxanthines display distinct compound-specific modulating effects. Full article

Oxidative stress is a key contributor to the onset and progression of diverse pathological conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD), neurodegeneration, cardiovascular disorders, and cancer. Conventional antioxidant therapies, such as small-molecule scavengers or systemic enzyme administration, are limited by poor stability, inefficient delivery, and off-target effects. Extracellular vesicles (EVs), particularly exosomes, are increasingly recognized as natural carriers of antioxidant enzymes (AOEs), including catalase, superoxide dismutases, glutathione peroxidases, peroxiredoxins, and thioredoxin. These vesicles not only protect enzymes from degradation but also enable targeted delivery to recipient cells, where they can actively modulate redox homeostasis. In this review, we summarize current evidence for AOEs as bona fide EV cargo, outline mechanisms that govern their selective packaging and transfer, and highlight their roles in intercellular communication under physiological and pathological conditions. We also discuss emerging therapeutic applications of both natural and engineered EVs for redox modulation, along with the challenges of quantifying enzymatic activity, ensuring reproducibility, and scaling clinical translation. By integrating insights from cell biology, redox signaling, and translational research, we propose that EV-mediated AOE delivery represents a promising next-generation strategy for combating oxidative stress-related diseases. Full article

Multidrug resistance (MDR) presents a significant challenge in the treatment of glioblastoma. We evaluated six novel adamantane–sclareol hybrids that integrate a natural labdane diterpene scaffold with an adamantane moiety to address this issue. Compounds 2, 5, and 6 demonstrated the ability to bypass P-glycoprotein (P-gp)-mediated resistance in resistant U87-TxR cells and induced collateral sensitivity, with compound 2 exhibiting the highest selectivity for glioblastoma compared to normal glial cells. Mechanistic studies revealed that compounds 2 and 5 selectively triggered early apoptosis in MDR cells, significantly elevated levels of H₂O₂ and peroxynitrite, and disrupted mitochondrial membrane potential. Additionally, these compounds altered the expression of key genes involved in glutathione (GSH) and thioredoxin (Trx) antioxidant defense systems and increased ASK1 protein levels, indicating the activation of ROS-driven apoptotic signaling. Both compounds inhibited P-gp function, leading to enhanced intracellular accumulation of rhodamine 123 (Rho 123) and synergistically sensitized U87-TxR cells to paclitaxel (PTX). A preliminary Rag1 xenograft study demonstrated that compound 5 effectively suppressed tumor growth without causing significant weight loss. Collectively, these findings position adamantane–sclareol hybrids, particularly compounds 2 and 5, as promising strategies that exploit an MDR-associated reactive oxygen species (ROS) vulnerability, combining selective cytotoxicity, redox disruption, and P-gp modulation to eliminate resistant glioblastoma cells and enhance the efficacy of chemotherapeutics. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by persistent inflammation and oxidative stress. Ilex paraguariensis (yerba mate) contains bioactive compounds—particularly chlorogenic acids, quercetin, and rutin—with documented antioxidant and anti-inflammatory properties. Objectives: To systematically review the mechanistic and clinical evidence on Ilex paraguariensis and its main constituents in RA-relevant inflammatory, oxidative, and bone metabolic pathways. Methods: Following PRISMA 2020, PubMed/MEDLINE, LILACS, and SciELO were searched up to September 2025. Eligible studies included yerba mate preparations (last 10 years) or isolated compounds (last 5 years) assessing RA-relevant clinical, inflammatory, oxidative, or bone metabolic outcomes. Non-original studies were excluded. Owing to heterogeneity, findings were narratively synthesized, and risk of bias was evaluated using RoB 2, ROBINS-I, OHAT, and SYRCLE. Results: Twenty-three studies met inclusion criteria: 11 human (clinical or observational), 7 human-based in vitro, and 5 animal studies. Interventions with yerba mate infusions or standardized extracts suggest reductions in inflammatory markers (e.g., C-reactive protein, interleukin-6) and indicate improvements in glutathione-related oxidative balance. Evidence from isolated compounds, particularly quercetin and rutin, suggests comparable anti-inflammatory and antioxidant effects. Preclinical studies appear to indicate modulation of inflammatory and redox pathways relevant to RA. Conclusions: Yerba mate and its constituents show preliminary indications of anti-inflammatory and antioxidant effects with potential relevance to RA pathophysiology. However, in the absence of clinical trials in RA patients, conclusions remain tentative, constrained by small sample sizes, methodological heterogeneity, species differences, and internal validity concerns. Future research should include rigorously designed randomized trials and mechanistic studies using advanced human-relevant platforms, such as organoids and organ-on-chip systems. Full article

Astrocytes play a key role in maintaining redox balance and supporting neuronal survival within the central nervous system (CNS). Their antioxidant machinery, primarily involving the Nrf2–ARE (nuclear factor erythroid 2-related factor 2–antioxidant response element) pathway, glutathione (GSH) metabolism, and mitochondrial function, enables the removal of reactive oxygen and nitrogen species (ROS and RNS) and supports neuronal resistance to oxidative stress. Effective communication between neurons and astrocytes coordinates metabolic and antioxidative responses via glutamate-, nitric oxide-, and calcium-dependent signalling. Disruption of this crosstalk during traumatic injury, ischemia, or neurodegenerative disease causes redox imbalance, neuroinflammation, and excitotoxicity, which contribute to progressive neurodegeneration. Astrocytic Nrf2 activation reduces oxidative damage and inflammation, while its suppression encourages a neurotoxic glial phenotype. Current evidence emphasizes various therapeutic strategies targeting astrocytic redox mechanisms, including small-molecule Nrf2 activators, GSH precursors, mitochondria-targeted antioxidants (MTAs), and RNA- and gene-based approaches. These interventions boost the antioxidant ability of astrocytes, influence reactive cell phenotypes, and support neuronal recovery in preclinical models. Although there are still challenges in delivery and safety, restoring neuron–glia redox signalling offers a promising strategy for neuroprotective treatments aimed at reducing oxidative stress-related CNS injury and disease progression. Full article