{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:00:54Z","timestamp":1785416454418,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US Department of War, Defense Health Affairs","award":["75-13266"],"award-info":[{"award-number":["75-13266"]}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education","doi-asserted-by":"crossref","award":["Institute of Nuclear Chemistry and Technology statutory"],"award-info":[{"award-number":["Institute of Nuclear Chemistry and Technology statutory"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]},{"award":["Institute of Nuclear Chemistry and Technology statutory"],"award-info":[{"award-number":["Institute of Nuclear Chemistry and Technology statutory"]}],"id":[{"id":"https:\/\/ror.org\/05dwvd537","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gamma-tocotrienol (GT3) is one of the constituents of vitamin E that demonstrated significant radioprotective efficacy in murine and nonhuman primate (NHP) models. Considering the antioxidant activity of GT3 and its role in terminating lipid peroxidation, we hypothesize that mechanism of radioprotective effect of GT3 may involve the inhibition of irradiation-induced ferroptosis\u2014a form of regulated cell death characterized by excessive, iron-dependent, peroxidation of lipids in cellular membranes. To test this hypothesis, the metabolomic and proteomic data from serum samples of GT3- or vehicle-treated NHPs exposed to 12 Gy (partial- or total-body) radiation was analyzed with focus on lipid peroxidation markers and proteins involved in iron metabolism. Four secondary lipid peroxidation products were identified including 4-oxo-2-nonenal (4-ONE), 4-hydroperoxy-2-nonenal (4-HPNE), 3,4-epoxynonanal (3,4-ENA), and trans-4,5-epoxy-(2E)-decenal (4,5-EDE). In vehicle-treated animals, their concentrations increased significantly as soon as 4 h after irradiation and then gradually declined. GT3 treatment mitigated this radiation-induced increase. In addition to lipid peroxidation products, similar patterns of change were observed for several polyunsaturated, monounsaturated, and saturated fatty acids as well as amino acids such as lysine and its derivatives. Taken together, these metabolomic changes suggest that irradiation induces cellular membrane damage through enhanced lipid peroxidation, while GT3 exerts a protective effect against this process. In addition, GT3 increased serum levels of haptoglobin and hemopexin\u2014two plasma scavenger proteins that play complementary protective roles in iron and heme homeostasis. Although the present study does not conclusively demonstrate that GT3 mediates radioprotection via inhibition of ferroptosis, the data suggest that GT3 limits membrane damage and reduces susceptibility to ferroptosis by enhancing iron and heme scavenging. Further investigation into the interaction between GT3 and key components of ferroptosis following exposure to ionizing radiation is therefore warranted.<\/jats:p>","DOI":"10.3390\/ijms27083387","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T13:09:31Z","timestamp":1775740171000},"page":"3387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Radiation Countermeasure Gamma-Tocotrienol Inhibits Accumulation of Lipid Peroxidation Products in the Serum of Nonhuman Primates Exposed to Partial- or Total-Body Radiation\u2014A Hallmark of Inhibition of Irradiation-Induced Ferroptosis?"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-5100","authenticated-orcid":false,"given":"Kamil","family":"Brz\u00f3ska","sequence":"first","affiliation":[{"name":"Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2108-2274","authenticated-orcid":false,"given":"Alana D.","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2645-7570","authenticated-orcid":false,"given":"Sarah A.","family":"Petrus","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-3849","authenticated-orcid":false,"given":"Vijay K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","first-page":"140","article-title":"Ferroptosis Is a Pivotal Player in Radiation-Induced Cell Death of Colorectal Cancer Cells","volume":"205","author":"Kerkhove","year":"2026","journal-title":"Radiat. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev-nutr-062320-114541","article-title":"Nutritional and Metabolic Control of Ferroptosis","volume":"42","author":"Mishima","year":"2022","journal-title":"Annu. Rev. 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