AntioxidantsPub Date : 2025-06-05DOI: 10.3390/antiox14060685
Urban Alehagen, Jan Olav Aaseth, Lutz Schomburg, Trine B Opstad, Anders Larsson, Jan Alexander
{"title":"Selenium and Coenzyme Q<sub>10</sub> Supplementation and Sex Differences in Cardiovascular Mortality Results from a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly People Low in Selenium.","authors":"Urban Alehagen, Jan Olav Aaseth, Lutz Schomburg, Trine B Opstad, Anders Larsson, Jan Alexander","doi":"10.3390/antiox14060685","DOIUrl":"10.3390/antiox14060685","url":null,"abstract":"<p><p><b>Background:</b> Low selenium intake and age-related decline of coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>) have been associated with an increased risk of cardiovascular disease (CVD) and oxidative stress. In a randomised placebo-controlled trial (RTC) in elderly people with low selenium levels, the supplementation with selenium and CoQ<sub>10</sub> reduced CVD and mortality. However, whether the supplementation elicited sex-specific benefits remained to be explored. <b>Methods:</b> Elderly Swedish persons (<i>n</i> = 443; balanced sex ratio) receiving selenium yeast (200 µg/day) and CoQ<sub>10</sub> (200 mg/day) combined or a placebo for four years were followed for additional six years. The response to supplementation, cardiovascular (CV) mortality, and risk factors were determined at four and ten years. Kaplan-Meier analyses, ANCOVA, repeated measurements of variance, and Cox proportional hazard regression analyses were performed. <b>Results:</b> The measured 10-year CV mortality rate was lower in females, and supplementation reduced this risk to a greater extent compared to in males. The improved survival rate apparently kicked in later in females than in males. At baseline, males had a higher smoking rate, increased inflammation and oxidative stress, and a higher prevalence of more advanced ischaemic heart disease (IHD) and signs of heart failure. When stratified by sex, in individuals with IHD, the intervention improved CV survival in both sexes, whereas supplementation had a more pronounced effect in females without IHD at inclusion. Supplementation diminished inflammation and oxidative stress, impaired the increase of NT-proBNP, and improved renal function in both sexes. <b>Conclusions</b>: The supplementation improved CV survival, especially in women. The higher prevalence of structural CVD and smoking in males may have contributed to the observed greater supplementation benefits in females. The preventive impact of selenium and CoQ<sub>10</sub> supplementation in elderly males and females may be particularly strong and meaningful in the early stages of CVD development.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Hydrolyzed Soybean Protein Enhances Oxidative Stress Resistance in <i>C. elegans</i> and Modulates Gut-Immune Axis in BALB/c Mice.","authors":"Jun Liu, Yansheng Zhao, Fei Leng, Xiang Xiao, Weibo Jiang, Shuntang Guo","doi":"10.3390/antiox14060689","DOIUrl":"10.3390/antiox14060689","url":null,"abstract":"<p><p>Soy protein isolate (SPI) is a high-purity protein from defatted soybeans, providing emulsifying and gelling functions for plant-based foods and supplements. Hydrolysis can facilitate the production of bioactive small-molecule proteins or peptides with potential functional applications. In this study, 20% hydrolyzed soy protein (20% HSP) was prepared from SPI, and the effects of 20% HSP and SPI on alleviating oxidative stress in <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) and regulating immune-gut microbiota in cyclophosphamide (CTX)-induced immunocompromised BALB/c mice were investigated. In <i>C. elegans</i>, both SPI and 20% HSP (300 μg/mL) enhanced locomotive activities, including body bending and head thrashing, and improved oxidative stress resistance under high glucose conditions. This improvement was mediated by increased antioxidant enzyme activities (SOD, CAT, and GSH-Px), while malondialdehyde (MDA) content was reduced by 60.15% and 82.28%, respectively. Both of them can also significantly extend the lifespan of normal <i>C. elegans</i> and paraquat-induced oxidative stress models by inhibiting lipofuscin accumulation. This effect was mediated through upregulation of <i>daf-16</i> and suppression of <i>daf-2</i> and <i>akt-1</i> expression. In immunocompromised mice, 20% HSP alleviated CTX-induced immune dysfunction by increasing peripheral white blood cells and lymphocytes, attenuating thymic atrophy, and reducing hepatic oxidative stress via MDA inhibition. Gut microbiota analysis revealed that 20% HSP restored microbial balance by suppressing <i>Escherichia-Shigella</i> and enriching beneficial genera, like <i>Psychrobacter</i>. These findings highlight 20% HSP and SPI's conserved anti-aging mechanisms via <i>daf-16</i> activation in <i>C. elegans</i> and immune-gut modulation in mice, positioning them as plant-derived nutraceuticals targeting oxidative stress and immune dysregulation.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-05DOI: 10.3390/antiox14060687
Lucia Longhitano, Stefano Forte, Laura Orlando, Stephanie Grasso, Alessandro Barbato, Nunzio Vicario, Rosalba Parenti, Paolo Fontana, Angela M Amorini, Giuseppe Lazzarino, Giovanni Li Volti, Michelino Di Rosa, Arcangelo Liso, Barbara Tavazzi, Giacomo Lazzarino, Daniele Tibullo
{"title":"Correction: Longhitano et al. The Crosstalk between GPR81/IGFBP6 Promotes Breast Cancer Progression by Modulating Lactate Metabolism and Oxidative Stress. <i>Antioxidants</i> 2022, <i>11</i>, 275.","authors":"Lucia Longhitano, Stefano Forte, Laura Orlando, Stephanie Grasso, Alessandro Barbato, Nunzio Vicario, Rosalba Parenti, Paolo Fontana, Angela M Amorini, Giuseppe Lazzarino, Giovanni Li Volti, Michelino Di Rosa, Arcangelo Liso, Barbara Tavazzi, Giacomo Lazzarino, Daniele Tibullo","doi":"10.3390/antiox14060687","DOIUrl":"10.3390/antiox14060687","url":null,"abstract":"<p><p>In the original publication, there was a mistake in Figure 4C as published [...].</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Culture Medium Enriched with Ultrafine Carbon Monoxide Bubbles Enhances In Vitro Blastocyst Formation of In Vivo-Fertilized Mouse Zygotes.","authors":"Toyofumi Hirakawa, Kazuhiko Nakabayashi, Noriko Ito, Keisuke Ishiwata, Daichi Urushiyama, Kohei Miyata, Tsukasa Baba, Kenichiro Hata, Shin'ichiro Yasunaga, Fusanori Yotsumoto, Katsuro Tachibana, Shingo Miyamoto","doi":"10.3390/antiox14060684","DOIUrl":"10.3390/antiox14060684","url":null,"abstract":"<p><p>Oxidative stress induced by in vitro culture conditions impedes the differentiation of fertilized zygotes. Gasotransmitters containing carbon monoxide (CO) exhibit antioxidant properties when exogenously administered at appropriate concentrations. In this study, CO was incorporated into ultrafine bubbles (UFBs) to devise an innovative method for promoting the efficient differentiation of fertilized mouse zygotes into blastocysts within an in vitro culture environment. While CO typically dissipates rapidly in culture media, its encapsulation into UFBs enabled its prolonged retention within the medium. Fertilized mouse zygotes cultured in the UFB medium exhibited a significantly higher rate of blastocyst hatching compared to those cultured in conventional media. Furthermore, Gene Ontology analysis revealed elevated expression of mitochondrial-related genes and genes essential for blastocyst maturation in the UFB culture medium. These findings underscore the potential of CO-UFB as a potent agent for improving in vitro blastocyst formation and hatching by mitigating oxidative stress, thereby offering a promising strategy for enhancing assisted reproductive technologies.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-04DOI: 10.3390/antiox14060683
Kye Man Cho, Se Hyeon Jeon, Eun Jeong Ko, Dong Hyun Park, Ye Ri Jeong, Du Yong Cho, Jeong Ho Kim, Jin Hwan Lee
{"title":"Multivariate Evaluation of Biofunctional Metabolites in Korean Soybean Cultivars by Use Categories: Assessment of Antioxidant and Enzyme Inhibition Activities.","authors":"Kye Man Cho, Se Hyeon Jeon, Eun Jeong Ko, Dong Hyun Park, Ye Ri Jeong, Du Yong Cho, Jeong Ho Kim, Jin Hwan Lee","doi":"10.3390/antiox14060683","DOIUrl":"10.3390/antiox14060683","url":null,"abstract":"<p><p>This research investigates the metabolite composition and biofunctional activiteies of 41 Korean soybeans, categorized by application: bean sprout, bean paste, vegetable, and cooked-with-rice. Isoflavones were identified via UPLC-Q-TOF-MS/MS and quantified using HPLC, revealing malonylgenistin as the predominant composition (average 743.4 μg/g, 42.3% of total isoflavones). Bean sprout showed the highest average isoflavone (2780.6 μg/g), followed by bean paste (1837.8 μg/g), cooked-with-rice (1448.2 μg/g), and vegetable (883.2 μg/g), with significant differences in individual cultivars. Protein ranged from 36.8 to 46.6% and oil from 17.0 to 22.3%, with vegetable soybeans exhibiting the highest average protein (44.9%) and lowest average oil (18.6%). Moreover, PLS-DA and hierarchical clustering revealed distinct metabolic patterns in usage groups. Antioxidant activities (radical scavenging; DNA protection) and enzyme inhibition (tyrosinase; α-glucosidase) also varied significantly, correlating with isoflavone distributions. Particularly, Sorog exhibited the highest isoflavone (3722.7 μg/g) and strong antioxidant activity (DPPH: 72.2%; ABTS: 93.8%, 500 μg/mL), DNA protection (92.8%, 200 μg/mL), and inhibition of tyrosinase and α-glucosidase by 78.4% and 84.2% (500 μg/mL). These findings suggest that isoflavone-rich bean sprout soybeans, especially Sorog, are promising candidates for health-promoting foods and functional cultivar development. This is the first systematic study comparing the metabolites and health-related properties of soybeans based on Korean usage categories.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-04DOI: 10.3390/antiox14060682
Manuela Martins-Green, Jane Kim, Klara Aziz
{"title":"The Impact of the Skin Microbiome and Oxidative Stress on the Initiation and Development of Cutaneous Chronic Wounds.","authors":"Manuela Martins-Green, Jane Kim, Klara Aziz","doi":"10.3390/antiox14060682","DOIUrl":"10.3390/antiox14060682","url":null,"abstract":"<p><p>Wound healing is a very complex process composed of several phases in which precise events occur, both temporally and specially. However, when these processes go awry, biofilm-forming bacteria become installed in the healing tissue, and the patient has comorbidities, so the wounds do not heal and become chronic. In this review, we describe the importance of high levels of oxidative stress (OS) and bacteria from the skin microbiome in the initiation and development of chronic wounds. The skin microbiome is diverse in humans, and its composition is dependent on the environment in the specific areas of the body. OS is critical for wound healing as it stimulates the immune system to destroy pathogens and secrete cytokines and growth factors that stimulate healing. When OS levels become high in the wound and the bacteria of the skin install themselves in the wound, chronicity ensues. However, neither OS nor the bacteria of the skin alone can initiate chronicity. However, when present together, chronic wounds develop. Given the complexity of chronic wound initiation, developing treatment for these wounds has been difficult. Here, we also discuss the challenges of treating chronic wounds and offer a potential sequence of approaches to treating these wounds after debridement.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimization of Ultrasound-Assisted Extraction of Phenolic Compounds from Romanian Blackthorn (<i>Prunus spinosa</i> L.) Fruits.","authors":"Ana-Maria Drăghici-Popa, Oana Cristina Pârvulescu, Raluca Stan, Ana-Maria Brezoiu","doi":"10.3390/antiox14060680","DOIUrl":"10.3390/antiox14060680","url":null,"abstract":"<p><p>Selecting factors that significantly affect the extraction process and optimizing them are essential to obtain high extraction efficiency. This study aimed at optimizing the ultrasonic-assisted extraction (UAE) of polyphenols from Romanian blackthorn fruits using aqueous solutions of ethanol as green extraction solvents. Six process factors, including solvent/plant material ratio (<i>R<sub>LS</sub></i> = 4.95-15.1 cm<sup>3</sup>/g), ethanol concentration in the extraction solvent (<i>c<sub>et</sub></i> = 16.4-83.6%), extraction temperature (<i>t</i> = 30-70 °C), pH of the solvent (<i>pH</i> = 2-7), amplitude of the ultrasonic probe (<i>A</i> = 30-70%), and extraction time (<i>τ</i> = 5-15 min), were screened and optimized based on a Plackett-Burman design (PBD) and a central composite design (CCD). Statistical analysis indicated that <i>R<sub>LS</sub></i>, <i>c<sub>et</sub></i>, and <i>t</i> significantly affected the process response variables in terms of total phenolic content (<i>TPC</i>), total anthocyanin content (<i>TAC</i>), and antioxidant capacity (<i>AC</i>). Under optimal conditions (<i>R<sub>LS</sub></i><sub>,<i>opt</i></sub> = 15.1 cm<sup>3</sup>/g, <i>c<sub>et</sub></i><sub>,<i>opt</i></sub> = 33.2%, <i>t<sub>opt</sub></i> = 66.8 °C, <i>pH<sub>opt</sub></i> = 7, <i>A<sub>opt</sub></i> = 50%, and <i>τ<sub>opt</sub></i> = 10 min), the following levels of response variables were experimentally determined: <i>TPC<sub>opt</sub></i> = 14.45 ± 0.718 mg GAE/g DM, <i>TAC<sub>opt</sub></i> = 0.405 ± 0.057 mg C3GE/g DM, and <i>AC<sub>opt</sub></i> = 16.75 ± 1.144 mg TE/g DM. Six phenolic compounds were identified in the extract obtained at optimal levels of process factors, i.e., rutin (7.12 ± 0.06 mg/100 g DM), protocatechuic acid (6.83 ± 0.01 mg/100 g DM), neochlorogenic acid (4.88 ± 0.01 mg/100 g DM), vanillic acid (3.70 ± 0.01 mg/100 g DM), chlorogenic acid (1.93 ± 0.02 mg/100 g DM), and caffeic acid (1.51 ± 0.01 mg/100 g DM).</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-03DOI: 10.3390/antiox14060677
Mirela Uzelac Božac, Danijela Poljuha, Slavica Dudaš, Josipa Bilić, Ivana Šola, Maja Mikulič-Petkovšek, Barbara Sladonja
{"title":"Phytochemical Profile and Antioxidant Properties of Invasive Plants <i>Ailanthus altissima</i> (Mill.) Swingle and <i>Helianthus tuberosus</i> L. in Istria Region, Croatia.","authors":"Mirela Uzelac Božac, Danijela Poljuha, Slavica Dudaš, Josipa Bilić, Ivana Šola, Maja Mikulič-Petkovšek, Barbara Sladonja","doi":"10.3390/antiox14060677","DOIUrl":"10.3390/antiox14060677","url":null,"abstract":"<p><p>Invasive alien plant species, while ecologically and economically problematic, represent an underutilized source of bioactive phytochemicals with promising phytopharmaceutical applications. This study investigates the LC-DAD-MS phenolic profiles of 70% ethanol and 80% methanol leaf and flower extracts of <i>Ailanthus altissima</i> (Mill.) Swingle and <i>Helianthus tuberosus</i> L., collected in the Istria region of Croatia, alongside their antioxidant capacities using ABTS, DPPH, and FRAP assays. Both species exhibited high levels of flavonoids and phenolic acids, with consistently higher concentrations in leaf versus flower tissues and in ethanolic versus methanolic extracts. Strong correlations (r > 0.9) between total phenolics and antioxidant activity confirmed the functional significance of these compounds. With a targeted metabolomics approach, in <i>A. altissima</i>, 51 phenolics were identified in leaves and 47 in flowers, with ellagitannins predominating; vescalagin isomers reached 94 mg/g DW in leaves and 82 mg/g DW in flowers. <i>H. tuberosus</i> extracts contained 34 phenolics in leaves and 33 in flowers, with hydroxycinnamic acids and flavonols dominating; 5-caffeoylquinic acid was the principal compound (25 mg/g DW in leaves, 2 mg/g DW in flowers). The identified phytochemicals are known for their potent antioxidant, anti-inflammatory, anticancer, antimicrobial, and metabolic-regulating properties. Additionally, four leaf-specific compounds were identified in each species, indicating potential for targeted extraction. These findings advance the phytochemical characterization of invasive taxa and highlight their potential as sources of natural antioxidants for functional food and pharmaceutical development.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-03DOI: 10.3390/antiox14060678
Che-Yu Chang, Rosario Hernández-Armengol, Kausik Paul, June Young Lee, Karina Nance, Tomohiro Shibata, Peibin Yue, Christian Stehlik, David R Gibb
{"title":"The Nrf2 Activator CDDO-Imidazole Suppresses Inflammation-Induced Red Blood Cell Alloimmunization.","authors":"Che-Yu Chang, Rosario Hernández-Armengol, Kausik Paul, June Young Lee, Karina Nance, Tomohiro Shibata, Peibin Yue, Christian Stehlik, David R Gibb","doi":"10.3390/antiox14060678","DOIUrl":"10.3390/antiox14060678","url":null,"abstract":"<p><p>Experimental Objective: During red blood cell (RBC) transfusion, inflammation promotes the production of anti-RBC alloantibodies that can cause significant hemolytic events. Avoiding RBC antigen exposure is the only strategy to prevent RBC alloimmunization in transfusion recipients. Identifying mechanisms that inhibit alloimmunization may lead to novel prophylactic interventions. One potential regulatory mechanism is the activation of the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), a master regulator of antioxidant pathways. Pharmacologic Nrf2 activators induce antioxidant production and improve the sequelae of inflammatory diseases. Thus, we tested the hypothesis that a Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]-imidazole (CDDO-Im), regulates inflammation-induced RBC alloimmunization.</p><p><strong>Methods: </strong>WT and <i>Nrf2</i>-deficient mice were treated with inflammatory stimuli and CDDO-Im prior to transfusion with RBCs expressing the KEL antigen (KEL+ RBCs). Anti-KEL IgM and IgG were measured in the serum of transfused mice. Nrf2-activated gene expression and interferon activity were measured in mice and human macrophages pre-treated with CDDO-Im and interferon stimuli.</p><p><strong>Results: </strong>Here, we report that CDDO-Im induces Nrf2-activated gene expression and inhibits type 1 interferon activity, which promotes RBC alloimmunization in transfusion models. In mice transfused with KEL+ RBCs, pre-treatment with CDDO-Im inhibited inflammation-induced anti-KEL antibody production and increased the post-transfusion recovery of KEL+ RBCs in a Nrf2-dependent manner. CDDO-Im also inhibited RBC alloimmunization in mice with pre-existing inflammation.</p><p><strong>Conclusions: </strong>These results indicate that the activation of the Nrf2 antioxidant pathway regulates RBC alloimmunization to the KEL antigen in a pre-clinical model. If these findings translate to other models and human studies, Nrf2 activators may represent a potential prophylactic intervention to inhibit alloimmunization.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2025-06-03DOI: 10.3390/antiox14060681
Yu-Long Sun, Shuai-Liang Zhang, Feng-Feng Zhou, Yuan-Xin Qian, Yang He, Run-Zhe Zhang, Fen Dong, Qiang Chen, Han-Ying Xu, Ji-Teng Wang, Yu-Ting Deng, Tao Han
{"title":"Arginine-Mediated Liver Immune Regulation and Antioxidant Defense in Largemouth Bass (<i>Micropterus salmoides</i>): Multi-Omics Insights into Metabolic Remodeling During <i>Nocardia seriolae</i> Infection.","authors":"Yu-Long Sun, Shuai-Liang Zhang, Feng-Feng Zhou, Yuan-Xin Qian, Yang He, Run-Zhe Zhang, Fen Dong, Qiang Chen, Han-Ying Xu, Ji-Teng Wang, Yu-Ting Deng, Tao Han","doi":"10.3390/antiox14060681","DOIUrl":"10.3390/antiox14060681","url":null,"abstract":"<p><p>The liver of fish is an essential metabolic organ that also serves an immune regulatory role. In this study, we constructed a model of largemouth bass (<i>Micropterus salmoides</i>) infected with <i>Nocardia seriolae</i> by injection to explore the immune and antioxidant functions of the liver. The results showed that <i>N. seriolae</i> infection caused severe pathological changes in the liver, including cell necrosis, granuloma formation, and leukocyte infiltration. The level of mRNA expression of immune-related genes in the liver was significantly increased 2 days post-infection. Moreover, the combined analysis of transcriptome and metabolome showed that <i>N. seriolae</i> infection markedly affected liver metabolism, including glutathione metabolism, arginine and proline metabolism, arachidonic acid metabolism, as well as starch and sucrose metabolism. Additionally, multiple key biomarkers were identified as involved in regulating responses to <i>N. seriolae</i> infection, including arginine, glutathione, <i>gpx</i>, <i>GST</i>, <i>PLA2G</i>, <i>GAA</i>, and <i>PYG</i>. To further elucidate the regulatory effects of arginine on the immune and antioxidant processes in the liver, primary hepatocytes were isolated and cultured. The results demonstrated that arginine supplementation significantly reduced the expression of LPS-induced apoptosis-related genes (<i>bax</i>, <i>cas3</i>, <i>cas8</i>, and <i>cas9</i>) by up to 50% while increasing the expression of antioxidant genes (<i>gpx</i>, <i>GST</i>) by up to 700% at 24 h. Through the analysis of metabolic changes and immune responses in the liver following <i>N. seriolae</i> infection, combined with in-vitro experiments, this study elucidated the anti-apoptotic and antioxidant effects of arginine, revealing the immune response mechanisms in fish liver and laying the groundwork for using nutritional strategies to improve fish health.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}