{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T22:22:27Z","timestamp":1776982947966,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Fanconi anemia (FA) is a rare bone marrow failure disorder characterized at the cellular level by hypersensitivity to alkylating agents, such as diepoxybutane (DEB), and redox imbalance. Alterations in red blood cells (RBCs), which play a key role in systemic antioxidant defense, are among the earliest changes in FA, consistent with an oxidative stress (OS) profile. Previous studies about antioxidant activity in RBCs from these patients are scarce and inconsistent. This study aimed to better understand the antioxidant profile in RBCs from FA patients carrying the homozygous FANCA c.295C&gt;T variant. Glutathione content and the activities of catalase, superoxide dismutase, glutathione peroxidase (GPx), and Pi-class glutathione S-transferase (GSTP1) were quantified, both at baseline and after culture with and without DEB, in RBCs from FA patients, FA carriers, and controls. At baseline, FA RBCs displayed significantly reduced catalase activity, whereas GPx and GSTP1 activities were significantly increased, suggesting an OS preconditioning state, not observed in RBCs from FA carriers and controls. Under culture and DEB exposure, FA RBCs exhibited a significant decline in both GSTP1 and GPx activities, contrary to controls. These new findings highlight a key role of GSTP1 and GPx activities in baseline antioxidant defense, severely compromised in case of increased OS toxicity.<\/jats:p>","DOI":"10.3390\/antiox14101150","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:48:37Z","timestamp":1758635317000},"page":"1150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Red Blood Cell Antioxidant State in Fanconi Anemia: The Highlighted Roles of Pi-Class Glutathione S-Transferase and Glutathione Peroxidase"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0556-406X","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Oliveira","sequence":"first","affiliation":[{"name":"Cytogenetics Laboratory, Department of Microscopy, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7430-6297","authenticated-orcid":false,"given":"Ricardo Jorge","family":"Dinis-Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory i4HB\u2014Institute for Health and Bioeconomy, CESPU\u2014University Institute of Health Sciences, 4585-116 Gandra, Portugal"},{"name":"UCIBIO\u2014Research Unit on Applied Molecular Biosciences, Translational Toxicology Research Laboratory, CESPU\u2014University Institute of Health Sciences, 4585-116 Gandra, Portugal"},{"name":"Department of Public Health and Forensic Sciences and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-3494","authenticated-orcid":false,"given":"F\u00e9lix","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6507-222X","authenticated-orcid":false,"given":"Paula","family":"Jorge","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory, Department of Microscopy, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4281-5438","authenticated-orcid":false,"given":"Beatriz","family":"Porto","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory, Department of Microscopy, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1172\/JCI92069","article-title":"Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia","volume":"127","author":"Knies","year":"2017","journal-title":"J. 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