Antioxidants最新文献

Donkey meat is valued for its high protein, unsaturated fats, and low cholesterol. Fatty acid (FA) composition critically influences meat quality and is modulated by dietary energy levels. Twenty-four meat donkeys (male) were randomly divided into three groups: a low-energy group (LEG), a medium-energy group (MEG), and a high-energy group (HEG). The trial lasted for 135 days, with dietary digestible energy levels adjusted during the pre-fattening, mid-fattening, and late-fattening phases according to the experimental design. The results showed that MEG and HEG interventions significantly upregulated tissue polyunsaturated fatty acid (PUFA) and n-3 PUFA content while reducing n-6/n-3 ratios, concomitant with enhanced activity and gene expression of most lipid-metabolizing enzymes. Notably, MEG further elevated antioxidant enzyme activities and anti-inflammatory mediators while suppressing pro-inflammatory factors. MEG and HEG significantly upregulated serum cholestane-3,7,12,25-tetrol-3-glucuronide and cortisol, along with hepatic choline, lysoPC(20:2(11Z,14Z)), glycocholic acid, and cholestane-3,7,12,25-tetrol-3-glucuronide. These modified metabolites were predominantly enriched in key metabolic pathways: pentose and glucuronate interconversions, primary bile acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, purine metabolism, and glutathione metabolism. Additionally, compared to HEG, MEG improved the antioxidant activities and immune signaling molecule levels with elevated pyroglutamic acid, glutathione, choline, inosine, adenine, and uric acid. Thus, moderately elevated dietary energy levels may enhance FA profiles in muscular and adipose tissues through coordinated regulation of lipid-metabolizing enzymes and associated gene expression, with serum and hepatic metabolites actively participating in these regulatory pathways. However, excessive energy intake could induce oxidative stress in donkeys.

Intracerebral hemorrhage (ICH) is a type of stroke with high mortality and disability rates. The hemoglobin and iron ions released by ruptured red blood cells after ICH can induce programmed cell death characterized by lipid peroxide accumulation-a defining feature of ferroptosis-which is one of the key mechanisms for the occurrence and progression of secondary brain injury after ICH. Betaine (BET), a natural amino acid derivative, is known to be an antioxidant, but its protective effect and molecular mechanisms in ICH-induced ferroptosis have not been studied yet. In this study, we investigated the effect of BET intervention on ICH-induced ferroptosis and possible mechanisms in vitro and in vivo, and we evaluated the expression of ferroptosis and oxidative stress molecules through in vivo and in vitro experiments. We analyzed the distribution of nuclear factor E2-related factor 2 (Nrf2) and assessed neurobehavioral function, hematoma volume, and iron content in the brain tissue of mice with ICH. BET upregulates nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling, reducing long-chain acyl-CoA synthetase 4 (ACSL4), reactive oxygen species (ROS), and malondialdehyde (MDA) while increasing glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels. It also decreases brain iron accumulation, aids hematoma clearance, and protects against ferroptosis and oxidative damage post ICH. Inhibition of Nrf2 with ML385 diminishes BET's neuroprotective effects, highlighting the pathway's importance in BET's mechanism of action. BET boosts antioxidant capacity via the Nrf2/HO-1 pathway; inhibits ferroptosis; reduces oxidative stress, brain edema, and iron accumulation post ICH; and aids hematoma clearance, offering neuroprotection.

The Keap1-Nrf2 signaling pathway is a central regulator of transcriptional responses to oxidative stress and is strongly linked to diverse pathologies, particularly cancer. In the cytoplasm, Keap1 (Kelch-like ECH-associated protein 1) promotes proteasomal degradation of Nrf2 (NF-E2-related factor 2). Oxidative stimuli disrupt the Keap1-Nrf2 interaction, facilitating Nrf2 nuclear accumulation and activation of antioxidant and detoxifying genes. Recent evidence suggests that Keap1 family proteins also enter the nucleus, bind chromatin, and regulate transcription, but the underlying mechanisms remain less understood. Here, we show that the Drosophila Keap1 ortholog, dKeap1, accumulates in the nucleus and gradually assembles stable nuclear foci in cells following oxidative treatment. FRAP analyses revealed reduced mobility of dKeap1 within these foci. Both the N-terminal (NTD) and C-terminal (CTD) domains of dKeap1 were required for foci formation. Two intrinsically disordered regions (IDRs) were identified within the CTD, and CTD-YFP fusion proteins readily formed condensates in vitro. Conversely, deletion of the Kelch domain resulted in robust cytoplasmic foci even under basal conditions, and in vitro assays also indicated that the Kelch domain suppresses dKeap1 condensate formation. Together, these findings reveal a novel molecular mechanism for the nuclear function of dKeap1, providing new insight into the broader roles of Keap1 factors in oxidative response, development, and disease.

Oocytes cultured in vitro are exposed to high oxygen tension and lack follicular antioxidants, leading to redox imbalance. Eicosapentaenoic acid (EPA), a marine long-chain n-3 polyunsaturated fatty acid, possesses strong antioxidant activity. Here, using pigs as a model, we examined the effects of EPA on oocyte in vitro maturation (IVM) and subsequent developmental competence. Cumulus-oocyte complexes were cultured with EPA, followed by assessment of nuclear and cytoplasmic maturation and embryonic development; transcriptomic and proteomic analyses were conducted to explore underlying mechanisms. Supplementation with 10 µM EPA significantly improved maturation and blastocyst rates by reducing spindle defects, facilitating a more uniform organization of cortical granules and mitochondria. EPA increased resolvin E1 accumulation and reduced cumulus-cell apoptosis through downregulation of TNF-α and BAX and upregulation of BCL2. In MII oocytes, EPA lowered apoptosis, DNA damage, and ROS levels while enhancing SOD2 and GPX4 expression. Mitochondrial quality and turnover were improved via upregulation of PPARGC1A, NDUFS2, PINK1, LC3, FIS1, MUL1, and OPA1, alongside strengthened ER-mitochondria contacts. These findings demonstrate that EPA alleviates oxidative stress, optimizes mitochondrial function, and enhances porcine oocyte maturation and developmental competence in a parthenogenetic model, highlighting its potential as a marine-derived functional additive for reproductive biotechnology. Future studies will be required to validate these effects under fertilization-based embryo production systems and to further refine dose-response relationships using expanded embryo-quality endpoints.

There is a growing demand for plant-derived antioxidants to replace synthetic ones in skincare applications. Phytochemicals are characterized by certain limitations, including poor bioavailability and chemical instability, which affect their industrial exploitation. Tomato peel extract has been used as a source of lycopene, which is renowned for its antioxidant properties. To improve the bioavailability of extracted lycopene, polymeric (poly-lactic-co-glycolic acid) nano-carriers were synthesized by comparing two non-ionic surfactants, polyvinyl alcohol (PVA) and Tween 20. The impact of surfactants has been studied by evaluating: (i) colloidal stability determined by dynamic light scattering; (ii) lycopene retention and bioactivity over time, as measured by spectrophotometric assays; (iii) biological interactions on 2D and 3D keratinocyte and melanocyte cell cultures. It was found that both surfactants enable the formation of stable lycopene-loaded nanoparticles suspensions; however, greater colloidal stability was exhibited by nanoparticles prepared with Tween 20. PVA, on the other hand, provided greater nanoparticle stability in terms of loaded lycopene retention and antioxidant activity. Tween 20 surfactant improves the internalization of lycopene-loaded nanoparticles in human skin spheroids. It was demonstrated that both surfactants provided excellent intracellular antioxidant activity of lycopene. This was observed in keratinocytes, melanocytes, adherent cells, and spheroids, suggesting potential skincare applications.

Fine particulate matter (PM2.5)-induced ovarian damage has attracted widespread attention, but differences in cytotoxicity and underlying mechanisms of water-soluble (WS-PM2.5) and water-insoluble (WIS-PM2.5) fractions are unclear. To investigate potential effects of PM2.5 from livestock farming environments on animal ovaries, PM2.5 samples were collected from large-scale cattle barns. There were significant differences between fractions regarding elemental composition, proportion of water-soluble ions, polycyclic aromatic hydrocarbon content, and endotoxin concentrations. Based on transcriptome sequencing results, in a cowshed PM2.5 exposure model (rats), differentially expressed ovarian mRNAs were significantly enriched in signaling pathways such as cytokine interaction and the Hippo pathway, with the expression of thioredoxin-interacting protein (Txnip) significantly increased. In vitro (primary rat ovarian granulosa cells), short-term exposure to WS-PM2.5 (12 h) significantly induced inflammatory factor release, acute oxidative stress, mitochondrial dysfunction, and intracellular Ca²⁺ overload, with characteristics of rapid acute injury. However, extended (24 h) WIS-PM2.5 exposure had greater disruptive effects on estrogen homeostasis, intracellular enzyme release (LDH), and mitochondrial structure (subacute characteristics). Furthermore, downregulating Txnip expression via inhibitors effectively mitigated cowshed PM2.5-induced ovarian granulosa cell toxicity, oxidative stress, and mitochondrial and hormonal dysfunction. In summary, solubility of cowshed PM2.5 components affected cytotoxic characteristics, and Txnip was a key factor linking oxidative stress to granulosa cell damage. The study provided a mechanistic basis and potential targets for preventing and controlling PM2.5-induced ovarian damage in livestock environments.

Oxidative stress (OS) is a major cause of defective sperm function. During laboratory handling, gametes are exposed to OS, potentially mitigated by in vitro antioxidant supplementation. This study evaluates the protective role of caffeic acid (CAF) on basal human semen and under induced OS. First, six semen samples from normozoospermic donors were incubated with CAF concentrations ranging from 50 to 500 µM at 37 °C for 2 h. Sperm motility and DNA integrity (acridine orange) were evaluated. Then, ten semen samples were divided into four aliquots and incubated, respectively, with CAF at 100 µM, H₂O₂ at 2 mM, or H₂O₂ at 2 mM + CAF at 100 µM, or untreated. Motility, DNA integrity, acrosome status (Pisum sativum agglutinin), OS quantified by F₂-isoprostanes (ELISA), and expression of Nrf2, Keap1, and HO-1 (qRT-PCR) were assessed. CAF at 100 µM improved progressive motility without damaging DNA and was selected for subsequent experiments. CAF showed protective effects on sperm damage induced by H₂O₂ treatment, restoring motility, DNA integrity, and acrosome status and reducing F₂-isoprostane levels. Nrf2 and HO-1 expression were upregulated by CAF, downregulated by H₂O₂, and restored by the co-treatment. CAF supplementation may protect human spermatozoa during in vitro handling by reducing OS, improving several sperm parameters, with a possible mechanism of action involving the Nrf2 pathway.

Vascular function is a direct factor affecting blood pressure, and it is a primary strategy for clinically controlling hypertension by regulating the constriction/relaxation of blood vessels. This study evaluates the vasodilatory and anti-hypertensive effects of norisoboldine (NOR), an isoquinoline alkaloid in Ayurvedic medicine. The rat thoracic aorta was isolated to investigate the vasodilatory effect, and L-NAME-induced hypertensive rats were established, respectively. In the isolated vascular ring, removal of the endothelium resulted in a significant decrease in the vasodilatory effect. Pretreatment with L-NAME, ODQ, KT5823, WT, Tri, Dilt, calcium-free solution, TG, Gd³⁺, 2-APB, Indo, 4-AP, Gli, and BaCl₂ inhibited the vasodilatory effect of NOR. In vascular endothelial cells, NOR promoted eNOS phosphorylation and inhibited TNF-α-induced expression of ICAM-1 and VCAM-1. SBP and DBP were significantly decreased after administration of different doses of NOR in the femoral vein of rats. In addition, NOR significantly reduced the blood pressure of L-NAME-induced hypertensive rats, up-regulated the serum levels of NO, cGMP, and CAT, and down-regulated MDA, IL-6, and TNF-α in hypertensive rats. NOR administration improved pathological changes in the thoracic aorta by regulating the arrangement of thoracic aortic smooth muscle cells, decreasing the thickness of the thoracic aortic wall, and reducing the degree of collagen deposition and fibrosis. In conclusion, the vasodilatory mechanisms of NOR were related to the Ca²⁺-eNOS signaling pathway, including the PGI₂ and various K⁺/Ca²⁺ channels, the inositol triphosphate receptor (IP₃R) calcium release, and the α-adrenergic receptor pathway. The anti-hypertensive mechanism of NOR may be related to increased NO and cGMP bioavailability, inhibition of oxidative stress and inflammatory responses, and improved vascular remodeling.

Early weaning in intensive lamb production improves reproductive efficiency but predisposes lambs to diarrhea, oxidative stress, and intestinal barrier dysfunction, highlighting the need for non-antibiotic strategies to protect gut health. This study evaluated whether a sheep-derived mixed probiotic could alleviate early weaning-induced intestinal injury and clarified its potential molecular mechanisms. Early weaning reduced body weight, average daily gain and feed efficiency, increased diarrhea, decreased plasma and colonic catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activities, increased malondialdehyde (MDA), elevated interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), reduced interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), increased plasma and mucosal immunoglobulin A, M, and G (IgA, IgM, IgG), and increased colonic lipopolysaccharide (LPS) with reduced diamine oxidase (DAO). Intestinally, EW induced villus atrophy, deeper crypts, lower villus height-to-crypt depth ratios, goblet cell loss, higher histopathological scores, and decreased colonic mucin 2, zonula occludens-1, claudin-1, and occludin. Probiotic supplementation partially reversed these alterations, restoring antioxidant enzyme activities, improving villus architecture and barrier protein expression, and rebalancing cytokine and immunoglobulin profiles. Transcriptomic and network analyses showed that early weaning activated Cytokine-cytokine receptor, NF-κB, TNF and Th17 pathways, whereas probiotics suppressed a weaning-responsive inflammatory gene module, downregulated key hub genes, and enhanced peroxisome proliferator-activated receptor (PPAR) signaling. These results show that supplementing early-weaned lambs with a mixed probiotic generated from sheep is an efficient nutritional strategy to reduce intestinal oxidative and inflammatory damage associated with weaning and to enhance their health and performance.

The increasing accumulation of plastic debris in aquatic environments has raised concerns about the ecotoxicological effects of polystyrene nanoplastics (PSNPs). This study examined PSNPs toxicity during a critical developmental stage by exposing 15 days post-fertilization (dpf) larvae of blotched snakehead (Channa maculata), an economically important freshwater fish, to PSNPs concentrations of 0.05-20 mg/L for 15 days. Histopathological analysis showed concentration-dependent damage, including hepatocellular vacuolization (5-10 mg/L) and hepatic sinusoidal dilation (20 mg/L) in the liver, alongside intestinal injuries ranging from villus erosion to rupture (5-20 mg/L). Biochemically, PSNPs triggered a biphasic oxidative response, where superoxide dismutase (SOD) and catalase (CAT) activities peaked at 5 mg/L before declining, while malondialdehyde (MDA) levels exhibited an opposite trend. Transcriptomic analysis and Quantitative real-time PCR (qRT-PCR) indicated that PSNPs disrupted growth, energy metabolism, and immune regulation in C. maculata larvae, evidenced by the dysregulation of growth hormone/insulin-like growth factor (GH/IGF) axis genes and up-regulation of immune-related genes. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) identified the heterogeneous nuclear ribonucleoproteins (HNRNP) gene family as hub genes from the key turquoise module, suggesting that PSNPs interfere with RNA processing and post-transcriptional control. In summary, PSNPs caused multi-level toxicity in C. maculata larvae, providing new insights into their ecotoxicological hazards in freshwater ecosystems.