AntioxidantsPub Date : 2025-07-18DOI: 10.3390/antiox14070889
Pasquale Pagliaro, Giuseppe Alloatti, Claudia Penna
{"title":"Cardioprotection Reloaded: Reflections on 40 Years of Research.","authors":"Pasquale Pagliaro, Giuseppe Alloatti, Claudia Penna","doi":"10.3390/antiox14070889","DOIUrl":"10.3390/antiox14070889","url":null,"abstract":"<p><p>Over the past four decades, cardioprotective research has revealed an extraordinary complexity of cellular and molecular mechanisms capable of mitigating ischemia/reperfusion injury (IRI). Among these, ischemic conditioning has emerged as one of the most influential discoveries: brief episodes of ischemia followed by reperfusion activate protective programs that reduce myocardial damage. These effects can be elicited locally (pre- or postconditioning) or remotely (remote conditioning), acting mainly through paracrine signaling and mitochondria-linked kinase pathways, with both early and delayed windows of protection. We have contributed to clarifying the roles of mitochondria, oxidative stress, prosurvival kinases, connexins, extracellular vesicles, and sterile inflammation, particularly via activation of the NLRP3 inflammasome. Despite robust preclinical evidence, clinical translation of these approaches has remained disappointing. The challenges largely stem from experimental models that poorly reflect real-world clinical settings-such as advanced age, comorbidities, and multidrug therapy-as well as the reliance on surrogate endpoints that do not reliably predict clinical outcomes. Nevertheless, interest in multi-target protective strategies remains strong. New lines of investigation are focusing on emerging mediators-such as gasotransmitters, extracellular vesicles, and endogenous peptides-as well as targeted modulation of inflammatory responses. Future perspectives point toward personalized cardioprotection tailored to patient metabolic and immune profiles, with special attention to high-risk populations in whom IRI continues to represent a major clinical challenge.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726772","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 : 2025-07-18DOI: 10.3390/antiox14070887
Tamara Martínez-Senra, Sonia Losada-Barreiro, Carlos Bravo-Díaz
{"title":"Effects of 2-Hydroxypropyl-β-Cyclodextrin on the Antioxidant Efficiency of Some Gallic Acid Derivatives in Soybean Oil-in-Water Emulsions.","authors":"Tamara Martínez-Senra, Sonia Losada-Barreiro, Carlos Bravo-Díaz","doi":"10.3390/antiox14070887","DOIUrl":"10.3390/antiox14070887","url":null,"abstract":"<p><p>Cyclodextrins (CDs) have been widely employed as natural host molecules to form inclusion complexes with bioactive molecules such as antioxidants. Their particular spatial configuration, in the form of truncated cones formed through α(1-4) ether linkages of glucopyranose units, makes them very appropriate for the formation of host-guest complexes, modifying their physicochemical properties and their location in multiphasic systems. Here, we investigated the effects of 2-hydroxypropyl-β-cyclodextrin (HPCD) on the efficiency of a series of gallic acid derivatives (propyl (PG), butyl (BG), octyl (OG), and lauryl (LG) gallates) in inhibiting the oxidation of soybean oil-in-water emulsions. For this purpose, we investigated the effects of HPCD on both the kinetics of lipid oxidation and the distribution of antioxidants in the same intact emulsions. The results show that in an aqueous solution, the antioxidants form 1:1 inclusion complexes with HPCD, with inclusion constants ranging from 383 M<sup>-1</sup> (PG) to 1946 M<sup>-1</sup> (OG). The results also show that the addition of HPCD to emulsions containing antioxidants does not lead to significant changes in their antioxidant effectiveness, with their efficiency being similar to that when no HPCD molecules are present. The results are interpreted in terms of the blocking effect exerted by the Tween 20 molecules, which act as effective guest competitors capable of removing the antioxidants from the HPCD cavity. The Tween 20 surfactant molecules need to be employed to stabilize the emulsions kinetically. This blocking effect, as a primary consequence, indicates that the interfacial concentration of the antioxidants, which is the region where the inhibition reaction takes place, remains constant; thus, their efficiency is not altered.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726789","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 : 2025-07-18DOI: 10.3390/antiox14070880
Tamara Merz, Sarah Ecker, Nicole Denoix, Oscar McCook, Stefanie Kranz, Ulrich Wachter, Edit Rottler, Thomas Papadopoulos, Christoph Fusch, Cosima Brucker, Jakob Triebel, Thomas Bertsch, Peter Radermacher, Christiane Waller
{"title":"Relationships Between H<sub>2</sub>S and OT/OTR Systems in Preeclampsia.","authors":"Tamara Merz, Sarah Ecker, Nicole Denoix, Oscar McCook, Stefanie Kranz, Ulrich Wachter, Edit Rottler, Thomas Papadopoulos, Christoph Fusch, Cosima Brucker, Jakob Triebel, Thomas Bertsch, Peter Radermacher, Christiane Waller","doi":"10.3390/antiox14070880","DOIUrl":"10.3390/antiox14070880","url":null,"abstract":"<p><p>Pre-eclampsia (PE) is a hypertensive pregnancy complication. Oxidative stress is hypothesized to contribute to the pathophysiology of PE. Both the hydrogen sulfide (H<sub>2</sub>S) and oxytocin (OT) systems might play a role in the pathophysiology of PE, like their antioxidant and hypotensive effects. Thus, the role of the interaction of the OT and H<sub>2</sub>S systems in the context of PE was further elucidated in the present clinical case-control study \"NU-HOPE\" (Nürnberg-Ulm: The role of H<sub>2</sub>S and Oxytocin Receptor in Pre-Eclampsia; ethical approval by the Landesärztekammer Bayern, file number 19033, 29 August 2019), comparing uncomplicated pregnancies, early onset PE (ePE, onset < 34 weeks gestational age) and late onset PE (lPE, onset > 34 weeks gestational age). Routine clinical data, serum H<sub>2</sub>S and homocysteine levels, and tissue protein expression, as well as nitrotyrosine formation, were determined. The main findings were (i) unchanged plasma sulfide levels, (ii) significantly elevated homocysteine levels in ePE, but not lPE, (iii) significantly elevated expression of H<sub>2</sub>S enzymes and OT receptor in the placenta in lPE, and (iv) significantly elevated nitrotyrosine formation in the lPE myometrium. Taken together, these findings suggest a role for the interaction of the endogenous H<sub>2</sub>S- and OT/OTR systems in the pathophysiology of pre-eclampsia, possibly linked to impaired antioxidant protection.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726851","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 : 2025-07-18DOI: 10.3390/antiox14070882
Aeyung Kim, Jinhee Kim, Chang-Seob Seo, Yu Ri Kim, Kwang Hoon Song, No Soo Kim
{"title":"Ethanolic Extract of Glycine Semen Preparata Prevents Oxidative Stress-Induced Muscle Damage in C2C12 Cells and Alleviates Dexamethasone-Induced Muscle Atrophy and Weakness in Experimental Mice.","authors":"Aeyung Kim, Jinhee Kim, Chang-Seob Seo, Yu Ri Kim, Kwang Hoon Song, No Soo Kim","doi":"10.3390/antiox14070882","DOIUrl":"10.3390/antiox14070882","url":null,"abstract":"<p><p>Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle degradation. Despite its clinical relevance, few effective therapeutic options are currently available. In this study, we investigated the protective effects of an ethanolic extract of Glycine Semen Preparata (GSP), i.e., fermented black soybeans, using in vitro and in vivo models of dexamethasone (Dexa)-induced muscle atrophy. In C2C12 myoblasts and myotubes, GSP significantly attenuated both oxidative stress-induced and Dexa-induced damages by reducing reactive oxygen species levels and by suppressing the expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. Moreover, GSP upregulated key genes involved in muscle regeneration (<i>Myod1</i> and <i>Myog</i>) and mitochondrial biogenesis (<i>PGC1α</i>), indicating its dual role in muscle protection and regeneration. Oral administration of GSP to mice with Dexa-induced muscle atrophy resulted in improved muscle fiber integrity, increased proportion of large cross-sectional area fibers, and partial recovery of motor function. Isoflavone aglycones, such as daidzein and genistein, were identified as active compounds that contribute to the beneficial effects of GSP through antioxidant activity and gene promoter enhancement. Thus, GSP is a promising nutraceutical that prevents or mitigates muscle atrophy by targeting oxidative stress and promoting myogenesis and mitochondrial function. Further studies are warranted to standardize the bioactive components and explore their clinical applications.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726790","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 : 2025-07-18DOI: 10.3390/antiox14070884
Jiang Li, Jiancheng Ma, Ya Li, Lan Luo, Wenhuan Zhang, Yong Tian, Yuncai Tian, Yi Li, Zhongjuan Wang, Mingyi Wu
{"title":"Antioxidant and Photoprotective Activities of <i>Viola philippica</i> Polyol Extracts.","authors":"Jiang Li, Jiancheng Ma, Ya Li, Lan Luo, Wenhuan Zhang, Yong Tian, Yuncai Tian, Yi Li, Zhongjuan Wang, Mingyi Wu","doi":"10.3390/antiox14070884","DOIUrl":"10.3390/antiox14070884","url":null,"abstract":"<p><p><i>Viola philippica</i> (VP), a traditional Chinese medicinal herb widely used for its antibacterial and antioxidant properties, has recently garnered attention for its potential in skin photoprotection. VP was extracted using glycerol (GLY), 1,3-propanediol (PDO), and 1,3-butanediol (BDO) at concentrations of 30%, 60%, and 90% (<i>w</i>/<i>w</i>) to evaluate its antioxidant and UV-protective properties. The total phenolic content (TPC) and total flavonoid content (TFC) of the nine extracts ranged from 34.73 to 71.45 mg GAEs/g and from 26.68 to 46.68 mg REs/g, respectively, with the highest TPC observed in 90% PDO and the highest TFC in 60% GLY. Antioxidant assays revealed IC<sub>50</sub> values of 0.49-1.26 mg/mL (DPPH), 0.10-0.19 mg/mL (ABTS), and 1.58-460.95 mg/mL (OH). Notably, the 60% GLY, 30% PDO, and 90% PDO extracts demonstrated notable protective effects against UVB-induced cell damage, reducing intracellular ROS levels and preventing DNA damage. RNA-seq analysis revealed that the protective effects were associated with the modulation of key molecular pathways, including neutrophil extracellular trap formation and TNF, IL-17, and HIF-1 signaling. These findings suggest that <i>Viola philippica</i> polyol extracts, particularly those using 60% GLY, 30% PDO, and 90% PDO, have promising potential for skin photoprotection and could be utilized as natural antioxidants in cosmetic formulations.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726751","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 : 2025-07-18DOI: 10.3390/antiox14070881
Aline Zuanazzi Pasinato, José Eduardo Vargas, Julia Spanhol da Silva, Joana Grandó Moretto, Cibele Ferreira Teixeira, Verônica Farina Azzolin, Ivana Beatrice Mânica da Cruz, Camile da Rosa Trevisan, Emanuele Cristina Zub, Renato Puga, Verónica Inés Vargas, Grethel León-Mejía, Rômulo Pillon Barcelos
{"title":"Guarana, Selenium, and L-Carnitine Supplementation Improves the Oxidative Profile but Fails to Reduce Tissue Damage in Rats with Osteoarthritis.","authors":"Aline Zuanazzi Pasinato, José Eduardo Vargas, Julia Spanhol da Silva, Joana Grandó Moretto, Cibele Ferreira Teixeira, Verônica Farina Azzolin, Ivana Beatrice Mânica da Cruz, Camile da Rosa Trevisan, Emanuele Cristina Zub, Renato Puga, Verónica Inés Vargas, Grethel León-Mejía, Rômulo Pillon Barcelos","doi":"10.3390/antiox14070881","DOIUrl":"10.3390/antiox14070881","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a progressive joint disease that is commonly managed with palliative drugs, many of which are associated with undesirable side effects. This study investigated the therapeutic potential of a novel supplementation with guarana, selenium, and L-carnitine (GSC) in a rat model of chemically induced OA. Forty male Wistar rats (8-9 weeks old) received intra-articular sodium monoiodoacetate (Mia) to induce OA, and were subsequently treated with GSC. Inflammatory and oxidative stress parameters were analyzed at the end of the experiment. GSC supplementation enhanced endogenous antioxidant defenses, suggesting systemic antioxidant activity. However, no histological improvement was observed. In silico analyses indicated that Mia-induced OA may involve a complex molecular environment that GSC, at the tested dose, failed to modulate at the site of injury. Despite the limited local effects, these findings support the systemic benefits of GSC and highlight the potential of natural compound-based strategies in OA management. Given the adverse effects of conventional pharmacotherapy, the development of alternative, naturally derived treatments remains a promising avenue for future research.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12293036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726800","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 : 2025-07-18DOI: 10.3390/antiox14070888
Laura Mourino-Alvarez, Inés Perales-Sánchez, Germán Hernández-Fernández, Gabriel Blanco-López, Emilio Blanco-López, Rocío Eiros, Cristian Herrera-Flores, Miryam González-Cebrian, Teresa Tejerina, Jesús Piqueras-Flores, Pedro Luis Sánchez, Luis F López-Almodóvar, Luis R Padial, Maria G Barderas
{"title":"The Influence of Diabetes Mellitus and Kidney Dysfunction on Oxidative Stress, a Reflection of the Multisystem Interactions in Aortic Stenosis.","authors":"Laura Mourino-Alvarez, Inés Perales-Sánchez, Germán Hernández-Fernández, Gabriel Blanco-López, Emilio Blanco-López, Rocío Eiros, Cristian Herrera-Flores, Miryam González-Cebrian, Teresa Tejerina, Jesús Piqueras-Flores, Pedro Luis Sánchez, Luis F López-Almodóvar, Luis R Padial, Maria G Barderas","doi":"10.3390/antiox14070888","DOIUrl":"10.3390/antiox14070888","url":null,"abstract":"<p><p>Progression of aortic stenosis (AS) is aggravated by type 2 Diabetes Mellitus (T2DM) and kidney dysfunction (KD). Oxidative stress is one of the main mechanisms that triggers AS and is also disturbed among subjects with T2DM and KD. Consequently, we studied the redox homeostasis in four groups of patients, also classifying each patient based on their kidney function: control subjects, T2DM, AS, and AS+T2DM. Free reduced thiols in plasma were analyzed using a colorimetric assay, and the redox state of human serum albumin (HSA) was assessed by immunodetection and PEG-PCMal labeling. Lower levels of thiols were evident in patients with AS and AS+T2DM, while reduced and mildly oxidized HSA was more abundant in T2DM and AS+T2DM patients, reflecting less protection against oxidation. Moreover, the thiol levels decreased as KD increased in patients with AS and AS+T2DM. Differences also exist in reduced and mildly oxidized HSA between patients with normal and severely impaired kidney function, whereas AS patients with severe KD had more strongly oxidized HSA. Our results confirm an imbalance in oxidative stress associated with AS that is aggravated by the coexistence of T2DM and KD. Moreover, T2DM treatment might mitigate this dysfunction, opening the door to new therapeutic approaches for these patients.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726894","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 : 2025-07-17DOI: 10.3390/antiox14070877
Jeongmin Lee, Seung Geun Yeo, Jae Min Lee, Sung Soo Kim, Jin-Woo Lee, Namhyun Chung, Dong Choon Park
{"title":"Expression of Free Radicals and Reactive Oxygen Species in Endometriosis: Current Knowledge and Its Implications.","authors":"Jeongmin Lee, Seung Geun Yeo, Jae Min Lee, Sung Soo Kim, Jin-Woo Lee, Namhyun Chung, Dong Choon Park","doi":"10.3390/antiox14070877","DOIUrl":"10.3390/antiox14070877","url":null,"abstract":"<p><p>This review explores the dual role of reactive oxygen species (ROS) and free radicals in the pathogenesis of endometriosis, aiming to deepen our understanding of these processes through a systematic literature review. To assess the induction and involvement of ROS in endometriosis, we conducted a comprehensive literature review using Cochrane Libraries, EMBASE, Google Scholar, PubMed, and SCOPUS databases. Of 30 qualifying papers ultimately reviewed, 28 reported a significant contribution of ROS to the pathogenesis of endometriosis, while two found no association. The presence of ROS in endometriosis is associated with infertility, irregular menstrual cycles, painful menstruation, and chronic pelvic discomfort. Among individual ROS types studied, hydrogen peroxide was most frequently investigated, followed by lipid peroxides and superoxide radicals. Notable polymorphisms associated with ROS in endometriosis include those for AT-rich interactive domain 1A (ARID1A) and quinone oxidoreductase 1 (NQO1) isoforms. Key enzymes for ROS scavenging and detoxification include superoxide dismutase, glutathione, and glutathione peroxidase. Effective inhibitors of ROS related to endometriosis are vitamins C and E, astaxanthin, fatty acid-binding protein 4, cerium oxide nanoparticles (nanoceria), osteopontin, sphingosine 1-phosphate, N-acetyl-L-cysteine, catalase, and a high-antioxidant diet. Elevated levels of ROS and free radicals are involved in the pathogenesis of endometriosis, suggesting that targeting these molecules could offer potential therapeutic strategies.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726794","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 High-Fat Diet Induces Oxidative Stress in OPA1<sup>+/-</sup> Mouse Cortices: A Critical Double Challenge.","authors":"Camille Champigny, Marlène Botella, Djamaa Atamena, Sébastien Bullich, Corentin Coustham, Bruno Guiard, Pascale Belenguer, Noélie Davezac","doi":"10.3390/antiox14070876","DOIUrl":"10.3390/antiox14070876","url":null,"abstract":"<p><p>A high-fat diet (HFD) has significant effects on health, leading to cardiovascular, metabolic, neurodegenerative, and psychiatric conditions and contributing to obesity and type 2 diabetes. Mitochondria, essential for energy production and oxidative metabolism, are adversely affected by a HFD, causing oxidative stress and impaired cellular function. Mutations in the <i>OPA1</i> (OPtic Atrophy 1) gene, crucial for mitochondrial dynamics and functions, are responsible for dominant optic atrophy (DOA), a mitochondrial neurodegenerative disease associated with increased reactive oxygen species (ROS). The expressivity of DOA is highly variable, even within the same family. This suggests that both modifying genetics and environmental factors could influence the penetrance of the disease. We previously demonstrated that genetic background modulates DOA expressivity and now ask if this is also the case for external cues. We thus explore how OPA1 deficiency interacts with HFD-induced metabolic disturbances, hypothesizing that long-term HFD consumption impairs brain mitochondrial function and disrupts oxidative metabolism. OPA1<sup>+/-</sup> mice were thus subjected to a HFD for a period of 12 weeks, and ROS levels and the expression of antioxidant genes were evaluated by Western blot and spectrophotometry. Cortices from high-fat diet-fed OPA1<sup>+/-</sup> mice showed lower aconitase activity than those of their wild-type (WT) litter mates, indicative of an unbalanced increase in mitochondrial ROS. Accordingly, OPA1<sup>+/-</sup> mice present lower levels of the antioxidant enzyme superoxide dismutase 2 compared to WT mice. Therefore, this study (i) reveals the onset of oxidative stress in brain cortices from OPA1<sup>+/-</sup> mice challenged with a HFD, (ii) shows that diet is a modifying factor for DOA, and (iii) suggests that food control could be used to moderate the severity of the disease.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12293076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726744","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 : 2025-07-17DOI: 10.3390/antiox14070878
Micol Caichiolo, Raffaella Margherita Zampieri, Francesca Terrin, Annachiara Tesoriere, Fabrizio Caldara, Nicoletta La Rocca, Paolo Martini, Luisa Dalla Valle
{"title":"Anti-Inflammatory Pathways Modulated by Microbial Polysaccharides from Euganean Thermal Muds in Zebrafish.","authors":"Micol Caichiolo, Raffaella Margherita Zampieri, Francesca Terrin, Annachiara Tesoriere, Fabrizio Caldara, Nicoletta La Rocca, Paolo Martini, Luisa Dalla Valle","doi":"10.3390/antiox14070878","DOIUrl":"10.3390/antiox14070878","url":null,"abstract":"<p><p>Thermal mud produced by spas of the Euganean Thermal District (Italy) has been used since ancient times for therapeutic purposes. Recently, the anti-inflammatory activity of microbial polysaccharides (M-PS), extracted from traditionally maturated muds, was demonstrated using the zebrafish model organism. However, the downstream signalling pathways regulated by M-PS remain largely unknown. In this study, to investigate the underlying mechanisms of inflammation resolution, we performed a transcriptome analysis on zebrafish larvae inflamed with copper sulphate and treated with M-PS. Our findings revealed that M-PS treatment down-regulated the expression of key genes involved in several inflammatory pathways. Gene Set Enrichment Analysis identified eleven up-regulated pathways (e.g., TNF-α signalling via NFκB, IL6-JAK-STAT signalling, p53 pathway, apoptosis, and interferon response) with components reduced in number and expression level in M-PS-treated larvae compared to the inflamed ones. Additionally, seven down-regulated pathways were identified (e.g., transcription factors E2F, MYC, and the G2M checkpoint). DEG-pseudotime analysis further confirmed the association of these genes with the pathways identified by GSEA. These results provide valuable insights into the anti-inflammatory properties of M-PS and the therapeutic potential of Euganean thermal muds for inflammatory diseases.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 7","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12292280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726749","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}