AntioxidantsPub Date : 2024-09-04DOI: 10.3390/antiox13091083
Paul-Henri Romeo, Laurine Conquet, Sébastien Messiaen, Quentin Pascal, Stéphanie G. Moreno, Anne Bravard, Jacqueline Bernardino-Sgherri, Nathalie Dereuddre-Bosquet, Xavier Montagutelli, Roger Le Grand, Vanessa Petit, Federica Ferri
{"title":"Multiple Mechanisms of Action of Sulfodyne®, a Natural Antioxidant, against Pathogenic Effects of SARS-CoV-2 Infection","authors":"Paul-Henri Romeo, Laurine Conquet, Sébastien Messiaen, Quentin Pascal, Stéphanie G. Moreno, Anne Bravard, Jacqueline Bernardino-Sgherri, Nathalie Dereuddre-Bosquet, Xavier Montagutelli, Roger Le Grand, Vanessa Petit, Federica Ferri","doi":"10.3390/antiox13091083","DOIUrl":"https://doi.org/10.3390/antiox13091083","url":null,"abstract":"Few therapeutic options are available to treat COVID-19. The KEAP1/NRF2 pathway, the major redox-responsive pathway, has emerged as a potential therapeutic target for COVID-19 as it regulates redox homeostasis and inflammation that are altered during SARS-CoV-2 infection. Here, we characterized the effects of NRF2-agonist Sulfodyne®, a stabilized natural Sulforaphane, in cellular and animal models of SARS-CoV-2 infection. In pulmonary or colonic epithelial cell lines, Sulfodyne® elicited a more efficient inhibition of SARS-CoV-2 replication than NRF2-agonists DMF and CDDO. This antiviral activity was not dependent on NRF2 but was associated with the regulation of several metabolic pathways, including the inhibition of ER stress and mTOR signaling, which are activated during SARS-CoV-2 infection. Sulfodyne® also decreased SARS-CoV-2 mediated inflammatory responses by inhibiting the delayed induction of IFNB1 and type I IFN-stimulated genes in infected epithelial cell lines and by reducing the activation of human by-stander monocytes recruited after SARS-CoV-2 infection. In K18-hACE2 mice infected with SARS-CoV-2, Sulfodyne® treatment reduced both early lung viral load and disease severity by fine-tuning IFN-beta levels. Altogether, these results provide evidence for multiple mechanisms that underlie the antiviral and anti-inflammatory activities of Sulfodyne® and pinpoint Sulfodyne® as a potent therapeutic agent against pathogenic effects of SARS-CoV-2 infection.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-09-04DOI: 10.3390/antiox13091081
Reinhart Speeckaert, Marijn M. Speeckaert, Nanja van Geel
{"title":"The Multifaceted Aspects of Oxidative Stress in the Skin and Other Tissues","authors":"Reinhart Speeckaert, Marijn M. Speeckaert, Nanja van Geel","doi":"10.3390/antiox13091081","DOIUrl":"https://doi.org/10.3390/antiox13091081","url":null,"abstract":"Different tissues experience various levels of oxidative stress based on their function and protection from outside environments [...]","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-09-04DOI: 10.3390/antiox13091082
Luisa Frusciante, Michela Geminiani, Behnaz Shabab, Tommaso Olmastroni, Giorgia Scavello, Martina Rossi, Pierfrancesco Mastroeni, Collins Nyaberi Nyong’a, Laura Salvini, Stefania Lamponi, Maria Laura Parisi, Adalgisa Sinicropi, Lorenzo Costa, Ottavia Spiga, Alfonso Trezza, Annalisa Santucci
{"title":"Exploring the Antioxidant and Anti-Inflammatory Potential of Saffron (Crocus sativus) Tepals Extract within the Circular Bioeconomy","authors":"Luisa Frusciante, Michela Geminiani, Behnaz Shabab, Tommaso Olmastroni, Giorgia Scavello, Martina Rossi, Pierfrancesco Mastroeni, Collins Nyaberi Nyong’a, Laura Salvini, Stefania Lamponi, Maria Laura Parisi, Adalgisa Sinicropi, Lorenzo Costa, Ottavia Spiga, Alfonso Trezza, Annalisa Santucci","doi":"10.3390/antiox13091082","DOIUrl":"https://doi.org/10.3390/antiox13091082","url":null,"abstract":"Repurposing saffron (Crocus sativus) waste presents a sustainable strategy for generating high-value products within the bioeconomy framework. Typically, flower components are discarded after stigma harvest, resulting in significant waste—350 kg of tepals per kilogram of stigmas. This research employed a comprehensive approach, integrating bioactivity studies (in vitro and in silico) with Life Cycle Assessment (LCA) evaluations, to extract and assess bioactive compounds from C. sativus tepals sourced in Tuscany, Italy. Phytochemical characterization using UPLC-MS/MS revealed a high abundance and variety of flavonoids in the hydro-ethanolic extract (CST). The antioxidant capacity was validated through various assays, and the ability to mitigate H2O2-induced oxidative stress and enhance fermentation was demonstrated in Saccharomyces cerevisiae. This study reports that C. sativus tepals extract reduces oxidative stress and boosts ethanol fermentation in yeast, paving the way for applications in the food and biofuels sectors. Further validation in RAW 264.7 macrophages confirmed CST’s significant anti-inflammatory effects, indicating its potential for pharmaceutical, cosmeceutical, and nutraceutical applications. In silico studies identified potential targets involved in antioxidant and anti-inflammatory processes, shedding light on possible interaction mechanisms with Kaempferol 3-O-sophoroside (KOS-3), the predominant compound in the extract. The integration of LCA studies highlighted the environmental benefits of this approach. Overall, this research underscores the value of using waste-derived extracts through “green” methodologies, offering a model that may provide significant advantages for further evaluations compared to traditional methodologies and supporting the circular bioeconomy.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-09-03DOI: 10.3390/antiox13091073
Camille M. Selvais, Maria A. Davis-López de Carrizosa, Romain Versele, Nicolas Dubuisson, Laurence Noel, Sonia M. Brichard, Michel Abou-Samra
{"title":"Challenging Sarcopenia: Exploring AdipoRon in Aging Skeletal Muscle as a Healthspan-Extending Shield","authors":"Camille M. Selvais, Maria A. Davis-López de Carrizosa, Romain Versele, Nicolas Dubuisson, Laurence Noel, Sonia M. Brichard, Michel Abou-Samra","doi":"10.3390/antiox13091073","DOIUrl":"https://doi.org/10.3390/antiox13091073","url":null,"abstract":"Sarcopenia, characterized by loss of muscle mass, quality, and function, poses significant risks in aging. We previously demonstrated that long-term treatment with AdipoRon (AR), an adiponectin receptor agonist, alleviated myosteatosis and muscle degeneration in middle-aged obese mice. This study aimed to determine if a shorter AR treatment could effectively offset sarcopenia in older mice. Two groups of old mice (20–23 months) were studied, one untreated (O) and one orally-treated with AR (O-AR) at 50 mg/kg/day for three months, compared with control 3-month-old young mice (Y) or 10-month-old young-adult mice (C-10). Results showed that AR remarkably inversed the loss of muscle mass by restoring the sarcopenia index and fiber count, which were greatly diminished with age. Additionally, AR successfully saved muscle quality of O mice by halving the accumulation of tubular aggregates and aberrant mitochondria, through AMPK pathway activation and enhanced autophagy. AR also bolstered muscle function by rescuing mitochondrial activity and improving exercise endurance. Finally, AR markedly curbed muscle fibrosis and mitigated local/systemic inflammation. Thus, a late three-month AR treatment successfully opposed sarcopenia and counteracted various hallmarks of aging, suggesting AR as a promising anti-aging therapy for skeletal muscles, potentially extending healthspan.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-09-03DOI: 10.3390/antiox13091076
Stefanie Endesfelder
{"title":"Caffeine: The Story beyond Oxygen-Induced Lung and Brain Injury in Neonatal Animal Models—A Narrative Review","authors":"Stefanie Endesfelder","doi":"10.3390/antiox13091076","DOIUrl":"https://doi.org/10.3390/antiox13091076","url":null,"abstract":"Caffeine is one of the most commonly used drugs in intensive care to stimulate the respiratory control mechanisms of very preterm infants. Respiratory instability, due to the degree of immaturity at birth, results in apnea of prematurity (AOP), hyperoxic, hypoxic, and intermittent hypoxic episodes. Oxidative stress cannot be avoided as a direct reaction and leads to neurological developmental deficits and even a higher prevalence of respiratory diseases in the further development of premature infants. Due to the proven antioxidant effect of caffeine in early use, largely protective effects on clinical outcomes can be observed. This is also impressively observed in experimental studies of caffeine application in oxidative stress-adapted rodent models of damage to the developing brain and lungs. However, caffeine shows undesirable effects outside these oxygen toxicity injury models. This review shows the effects of caffeine in hyperoxic, hypoxic/hypoxic-ischemic, and intermittent hypoxic rodent injury models, but also the negative effects on the rodent organism when caffeine is administered without exogenous oxidative stress. The narrative analysis of caffeine benefits in cerebral and pulmonary preterm infant models supports protective caffeine use but should be given critical consideration when considering caffeine treatment beyond the recommended corrected gestational age.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-09-03DOI: 10.3390/antiox13091074
Maria Cristina Barbalace, Michela Freschi, Irene Rinaldi, Lorenzo Zallocco, Marco Malaguti, Clementina Manera, Gabriella Ortore, Mariachiara Zuccarini, Maurizio Ronci, Doretta Cuffaro, Marco Macchia, Silvana Hrelia, Laura Giusti, Maria Digiacomo, Cristina Angeloni
{"title":"Unraveling the Protective Role of Oleocanthal and Its Oxidation Product, Oleocanthalic Acid, against Neuroinflammation","authors":"Maria Cristina Barbalace, Michela Freschi, Irene Rinaldi, Lorenzo Zallocco, Marco Malaguti, Clementina Manera, Gabriella Ortore, Mariachiara Zuccarini, Maurizio Ronci, Doretta Cuffaro, Marco Macchia, Silvana Hrelia, Laura Giusti, Maria Digiacomo, Cristina Angeloni","doi":"10.3390/antiox13091074","DOIUrl":"https://doi.org/10.3390/antiox13091074","url":null,"abstract":"Neuroinflammation is a critical aspect of various neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. This study investigates the anti-neuroinflammatory properties of oleocanthal and its oxidation product, oleocanthalic acid, using the BV-2 cell line activated with lipopolysaccharide. Our findings revealed that oleocanthal significantly inhibited the production of pro-inflammatory cytokines and reduced the expression of inflammatory genes, counteracted oxidative stress induced by lipopolysaccharide, and increased cell phagocytic activity. Conversely, oleocanthalic acid was not able to counteract lipopolysaccharide-induced activation. The docking analysis revealed a plausible interaction of oleocanthal, with both CD14 and MD-2 leading to a potential interference with TLR4 signaling. Since our data show that oleocanthal only partially reduces the lipopolysaccharide-induced activation of NF-kB, its action as a TLR4 antagonist alone cannot explain its remarkable effect against neuroinflammation. Proteomic analysis revealed that oleocanthal counteracts the LPS modulation of 31 proteins, including significant targets such as gelsolin, clathrin, ACOD1, and four different isoforms of 14-3-3 protein, indicating new potential molecular targets of the compound. In conclusion, oleocanthal, but not oleocanthalic acid, mitigates neuroinflammation through multiple mechanisms, highlighting a pleiotropic action that is particularly important in the context of neurodegeneration.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Effect of Light Intensity during Cultivation and Postharvest Storage on Mustard and Kale Microgreen Quality","authors":"Ieva Gudžinskaitė, Kristina Laužikė, Audrius Pukalskas, Giedrė Samuolienė","doi":"10.3390/antiox13091075","DOIUrl":"https://doi.org/10.3390/antiox13091075","url":null,"abstract":"Microgreens are vegetable greens that are harvested early while they are still immature and have just developed cotyledons. One of the disadvantages and a challenge in production is that they exhibit a short shelf life and may be damaged easily. In seeking to prolong the shelf life, some pre- and postharvest interventions have been investigated. Here, kale and mustard microgreens were grown in a controlled-environment walk-in chamber at +21/17 °C, with ~65% relative air humidity, while maintaining the spectral composition of deep red 61%, blue 20%, white 15%, and far red 4% (150, 200, and 250 µmol m−2 s−1 photosynthetic photon flux density (PPFD)). Both microgreens seemed to exhibit specific and species-dependent responses. Higher PPFD during growth and storage in light conditions resulted in increased contents of TPC in both microgreens on D5. Additionally, 150 and 250 PPFD irradiation affected the α-tocopherol content by increasing it during postharvest storage in kale. On D0 150 for kale and 200 PPFD for mustard microgreens, β-carotene content increased. D5 for kale showed insignificant differences, while mustard responded with the highest β-carotene content, under 150 PPFD. Our findings suggest that both microgreens show beneficial outcomes when stored in light compared to dark and that mild photostress is a promising tool for nutritional value improvement and shelf-life prolongation.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-09-02DOI: 10.3390/antiox13091072
Ignacio Silva-Llanes, Raquel Martín-Baquero, Alicia Berrojo-Armisen, Carmen Rodríguez-Cueto, Javier Fernández-Ruiz, Eva De Lago, Isabel Lastres-Becker
{"title":"Beneficial Effect of Dimethyl Fumarate Drug Repositioning in a Mouse Model of TDP-43-Dependent Frontotemporal Dementia","authors":"Ignacio Silva-Llanes, Raquel Martín-Baquero, Alicia Berrojo-Armisen, Carmen Rodríguez-Cueto, Javier Fernández-Ruiz, Eva De Lago, Isabel Lastres-Becker","doi":"10.3390/antiox13091072","DOIUrl":"https://doi.org/10.3390/antiox13091072","url":null,"abstract":"Frontotemporal dementia (FTD) causes progressive neurodegeneration in the frontal and temporal lobes, leading to behavioral, cognitive, and language impairments. With no effective treatment available, exploring new therapeutic approaches is critical. Recent research highlights the transcription factor Nuclear Factor erythroid-derived 2-like 2 (NRF2) as vital in limiting neurodegeneration, with its activation shown to mitigate FTD-related processes like inflammation. Dimethyl fumarate (DMF), an NRF2 activator, has demonstrated neuroprotective effects in a TAU-dependent FTD mouse model, reducing neurodegeneration and inflammation. This suggests DMF repositioning potential for FTD treatment. Until now, no trial had been conducted to analyze the effect of DMF on TDP-43-dependent FTD. In this study, we aimed to determine the potential therapeutic efficacy of DMF in a TDP-43-related FTD mouse model that exhibits early cognitive impairment. Mice received oral DMF treatment every other day from presymptomatic to symptomatic stages. By post-natal day (PND) 60, an improvement in cognitive function is already evident, becoming even more pronounced by PND90. This cognitive enhancement correlates with the neuroprotection observed in the dentate gyrus and a reduction in astrogliosis in the stratum lacunosum-moleculare zone. At the prefrontal cortex (PFC) level, a neuroprotective effect of DMF is also observed, accompanied by a reduction in astrogliosis. Collectively, our results suggest a potential therapeutic application of DMF for patients with TDP-43-dependent FTD.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-09-02DOI: 10.3390/antiox13091071
María Magallón, Silvia Castillo-Corullón, Lucía Bañuls, Teresa Romero, Daniel Pellicer, Alberto Herrejón, María Mercedes Navarro-García, Cruz González, Francisco Dasí
{"title":"Impact of Hypoxia on Neutrophil Degranulation and Inflammatory Response in Alpha-1 Antitrypsin Deficiency Patients","authors":"María Magallón, Silvia Castillo-Corullón, Lucía Bañuls, Teresa Romero, Daniel Pellicer, Alberto Herrejón, María Mercedes Navarro-García, Cruz González, Francisco Dasí","doi":"10.3390/antiox13091071","DOIUrl":"https://doi.org/10.3390/antiox13091071","url":null,"abstract":"Background: Alpha-1 antitrypsin deficiency (AATD) is an inflammatory disorder where neutrophils play a key role. Excessive neutrophil activation leads to local hypoxia and tissue damage. Most research on neutrophil function has been conducted under atmospheric conditions (21% O2), which may not represent physiological or pathological conditions. This study aimed to determine the effects of hypoxia on neutrophil degranulation and cytokine production in AATD patients. Methods: Neutrophils isolated from 54 AATD patients (31 MZ; 8 SZ; 15 ZZ) and 7 controls (MM) were exposed to hypoxia (1% O2) for 4 h. Neutrophil degranulation was assessed by measuring elastase (NE), myeloperoxidase (MPO), lactoferrin, and matrix metalloproteinase-9 (MMP-9) levels using immunoassay-based methods. Pro-inflammatory (IL-8, IL-1 beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-4 and IL-10) cytokine levels were assessed by a Luminex-based method. Results: Our results indicate a significantly increased release of NE (p = 0.015), MPO (p = 0.042), lactoferrin (p = 0.015), and MMP-9 (p = 0.001) compared to controls. Pro-inflammatory cytokines show a significant rise in IL-8 (p = 0.019), a trend towards increased IL-1 beta (p = 0.3196), no change in IL-6 (p = 0.7329), and reduced TNF-alpha (p = 0.006). Anti-inflammatory cytokines show increased IL-4 (p = 0.057) and decreased IL-10 (p = 0.05703). Conclusions: Increased neutrophil degranulation and inflammatory phenotype are observed in AATD neutrophils under physiological hypoxia.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AntioxidantsPub Date : 2024-09-02DOI: 10.3390/antiox13091070
Hannah D. Langlands, Deborah K. Shoemark, Ashley M. Toye
{"title":"Modulation of Antioxidant Enzyme Expression of In Vitro Culture-Derived Reticulocytes","authors":"Hannah D. Langlands, Deborah K. Shoemark, Ashley M. Toye","doi":"10.3390/antiox13091070","DOIUrl":"https://doi.org/10.3390/antiox13091070","url":null,"abstract":"The regulation of reactive oxygen species (ROS) in red blood cells (RBCs) is crucial for maintaining functionality and lifespan. Indeed, dysregulated ROS occurs in haematological diseases such as sickle cell disease and β-thalassaemia. In order to combat this, RBCs possess high levels of protective antioxidant enzymes. We aimed to further boost RBC antioxidant capacity by overexpressing peroxiredoxin (Prxs) and glutathione peroxidase (GPxs) enzymes. Multiple antioxidant enzyme cDNAs were individually overexpressed in expanding immortalised erythroblasts using lentivirus, including Prx isoforms 1, 2, and 6 and GPx isoforms 1 and 4. Enhancing Prx protein expression proved straightforward, but GPx overexpression required modifications. For GPx4, these modifications included adding a SECIS element in the 3’UTR, the removal of a mitochondrial-targeting sequence, and removing putative ubiquitination sites. Culture-derived reticulocytes exhibiting enhanced levels of Prx and GPx antioxidant proteins were successfully engineered, demonstrating a novel approach to improve RBC resilience to oxidative stress. Further work is needed to explore the activity of these proteins and their impact on RBC metabolism, but this strategy shows promise for improving RBC function in physiological and pathological contexts and during storage for transfusion. Enhancing the antioxidant capacity of reticulocytes has exciting promise for developing culture-derived RBCs with enhanced resistance to oxidative damage and offers new therapeutic interventions in diseases with elevated oxidative stress.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":null,"pages":null},"PeriodicalIF":7.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142208096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}