{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T14:25:57Z","timestamp":1784989557230,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Increased oxidative stress and apoptosis are key mechanisms of thymic atrophy induced by cyclophosphamide (CYP). Atrophy leads to changes in the thymic microenvironment and disrupts T cell maturation. The hormone melatonin displays antioxidant and antiapoptotic effects. Here, we tested the hypothesis that melatonin would act as a cytoprotective agent against the harmful effects of CYP in the thymus. A single dose of CYP (300\u2009mg\/kg; ip) was injected in male C57BL\/6 mice pretreated or not with melatonin (10\u2009mg\/kg\/day, ip) for 4 days. Atrophy, oxidative stress and apoptosis markers, and T cell subpopulations were evaluated in the thymus 24\u2009h after CYP injection. Melatonin partially prevented atrophy and the increase in caspase 3 activity induced by CYP. Augmented lipoperoxidation and generation of NADPH\u2010oxidase derived superoxide (O<jats:sub>2<\/jats:sub><jats:sup>\u2022\u2212<\/jats:sup>), as well as decreased superoxide dismutase (SOD) activity, were detected in the thymus of CYP\u2010injected mice. Pretreatment with melatonin abrogated these responses. CYP reduced the number of double\u2010positive (CD4<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>) cells, activated single\u2010positive (CD8<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>) cells, and regulatory CD4<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> (Treg) cells in the thymus. None of these effects were reversed by melatonin. In conclusion, melatonin partially prevented thymic atrophy, possibly by reducing apoptosis and oxidative stress. However, melatonin did not abrogate the immunomodulatory effect of CYP on T cell populations. The lack of effect of melatonin on CYP\u2010induced reduction in Treg cells may be of interest since these cells reduce antitumor immunity.<\/jats:p>","DOI":"10.1002\/cbf.70052","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T01:20:21Z","timestamp":1738286421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Melatonin Prevents Thymic Atrophy but Does Not Protect Against Disruption of T Cell Maturation Related to Cyclophosphamide Exposure"],"prefix":"10.1002","volume":"43","author":[{"given":"Gustavo F.","family":"Pimenta","sequence":"first","affiliation":[{"name":"Departamento de Farmacologia, Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Farmacologia, Faculdade de Medicina de Ribeir\u00e3o Preto Universidade de S\u00e3o Paulo (USP), Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"},{"name":"Departamento de Enfermagem Psiqui\u00e1trica, Laborat\u00f3rio de Farmacologia, Escola de Enfermagem de Ribeir\u00e3o Preto USP, Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thales M. 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B.","family":"de Souza","sequence":"additional","affiliation":[{"name":"Departamento de Enfermagem Psiqui\u00e1trica, Laborat\u00f3rio de Farmacologia, Escola de Enfermagem de Ribeir\u00e3o Preto USP, Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson","family":"Elias\u2010Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Faculdade de Medicina de Ribeir\u00e3o Preto USP, Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa F.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Faculdade de Medicina de Ribeir\u00e3o Preto USP, Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Carlos","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e 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