{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:01:23Z","timestamp":1791234083365,"version":"4.1.0"},"reference-count":28,"publisher":"Radiation Research Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2026,6,22]]},"abstract":"<jats:p>Radiation has beneficial medical and industrial applications; however, high-dose exposure during accidents can result in severe outcomes, including fatal bone marrow failure. Total-body irradiation (TBI) of 6\u201310 Gy induces hematopoietic failure, primarily due to oxidative stress caused by excessive reactive oxygen species. This study aimed to evaluate the protective potential of probucol, a potent antioxidant, against lethal ionizing radiation-induced damage. Eight-week-old mice received 8 Gy TBI. Two probucol treatment strategies were tested: pretreatment, in which the drug was administered daily for 4 days before irradiation, and post-treatment, in which the drug was administered 4 h after irradiation and continued for 4 days. Survival rates, peripheral blood cell counts, bone marrow and spleen morphology, and urinary excretion levels of 8-hydroxy-2\u2032-deoxyguanosine (oxidative DNA damage) were analyzed. Probucol pretreatment improved survival in mice that received 8 Gy TBI, whereas most of the mice in the post-treatment group and all of the mice in vehicle control group died within 30 days after exposure. Probucol pretreatments also significantly decreased the urinary excretion of 8-hydroxy-2\u2032-deoxyguanosine compared with untreated control mice. Although TBI caused pancytopenia in both groups, peripheral blood cell counts showed no difference between the groups on day 14 postirradiation. Probucol pretreatment preserved nucleated bone marrow cells and showed extramedullary hematopoiesis in the spleen. These findings suggest that probucol pretreatment exert beneficial effects by mitigating radiation-induced bone marrow suppression and promoting compensatory extramedullary hematopoiesis within the spleen through its antioxidative action.<\/jats:p>","DOI":"10.1667\/rade-26-00251.1","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:30:33Z","timestamp":1787841033000},"page":"284-291","source":"Crossref","is-referenced-by-count":0,"title":["Antioxidant Probucol Reduces Mortality in Mice Exposed to Lethal Doses of Ionizing Radiation"],"prefix":"10.1667","volume":"206","author":[{"given":"Shunsuke","family":"Tanigawa","sequence":"first","affiliation":[{"name":"Department of Regeneration and Medicine, Division of Radiation Medical Science Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki-ichiro","family":"Kawano","sequence":"additional","affiliation":[{"name":"Department of Regeneration and Medicine, Division of Radiation Medical Science Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Biology and Environmental Chemistry Division, Sustainable System Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farina Mohamad","family":"Yusoff","sequence":"additional","affiliation":[{"name":"Department of Regeneration and Medicine, Division of Radiation Medical Science Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Regeneration and Medicine, Division of Radiation Medical Science Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Maruhashi","sequence":"additional","affiliation":[{"name":"Department of Regeneration and Medicine, Division of Radiation Medical Science Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Kajikawa","sequence":"additional","affiliation":[{"name":"Department of Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Department of Regeneration and Medicine, Division of Radiation Medical Science Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Yamaji","sequence":"additional","affiliation":[{"name":"Department of Regeneration and Medicine, Division of Radiation Medical Science Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Mizobuchi","sequence":"additional","affiliation":[{"name":"Department of Regeneration and Medicine, Division of Radiation Medical Science Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihito","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Regeneration and Medicine, Division of Radiation Medical Science Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"26","doi-asserted-by":"crossref","unstructured":"T Yoshida, S Goto, M Kawakatsu, et al.  \"Free Radic Res.\"  46, \"Mitochondrial dysfunction, a probable cause of persistent oxidative stress after exposure to ionizing radiation.\" 147 (2012)","DOI":"10.3109\/10715762.2011.645207"},{"key":"25","doi-asserted-by":"crossref","unstructured":"RM Abolfath, DJ Carlson, ZJ Chen, et al.  \"Phys Med Biol.\"  58, \"A molecular dynamics simulation of DNA damage induction by ionizing radiation.\" 7143 (2013)","DOI":"10.1088\/0031-9155\/58\/20\/7143"},{"key":"21","doi-asserted-by":"crossref","unstructured":"Y Zhang, X Chen, X Wang, et al.  \"Stem Cell Res Ther.\"  15, \"Insights into ionizing radiation-induced bone marrow hematopoietic stem cell injury.\" 222 (2024)","DOI":"10.1186\/s13287-024-03853-7"},{"key":"9","doi-asserted-by":"crossref","unstructured":"M Redza-Dutordoir  and DA Averill-Bates  \"Biochim Biophys Acta Mol Cell Res.\"  1863, \"Activation of apoptosis signalling pathways by reactive oxygen species.\" 2977 (2016)","DOI":"10.1016\/j.bbamcr.2016.09.012"},{"key":"1","doi-asserted-by":"publisher","unstructured":"H D\u00f6rr  and V Meineke  \"BMC Med.\"  9, \"Acute radiation syndrome caused by accidental radiation exposure\u2014therapeutic principles.\" 126 (2011)","DOI":"10.1186\/1741-7015-9-126"},{"key":"2","doi-asserted-by":"publisher","unstructured":"I Maci\u00e0, M Garau, A Lucas Calduch, et al.  \"Rep Pract Oncol Radiother.\"  16, \"Radio-biology of the acute radiation syndrome.\" 123 (2011)","DOI":"10.1016\/j.rpor.2011.06.001"},{"key":"3","unstructured":"\"Medical Management of Radiation Injuries. Safety Reports Series No. 101.\"  2020"},{"key":"4","doi-asserted-by":"publisher","unstructured":"N Kekre  and JH Antin  \"Blood.\"  124, \"Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist.\" 334 (2014)","DOI":"10.1182\/ blood-2014-02-514760"},{"key":"5","unstructured":"\"Policy Recommendations for National Stockpiles for Radiation and Nuclear Emergencies.\"  2023"},{"key":"6","doi-asserted-by":"publisher","unstructured":"N Hamada, K Kawano, T Nomura, et al.  \"Cancers.\"  13, \"Vascular damage in the aorta of wild-type mice exposed to ionizing radiation: sparing and enhancing effects of dose protraction.\" 5344 (2021)","DOI":"10.3390\/cancers13215344"},{"key":"7","doi-asserted-by":"publisher","unstructured":"J Nuszkiewicz, A Wo\u017aniak, K Szewczyk-Golec,  \"Int J Mol Sci.\"  21, \"Ionizing radiation as a source of oxidative stress\u2014the protective role of melatonin and vitamin D.\" 5804 (2020)","DOI":"10.3390\/ijms21165804"},{"key":"8","doi-asserted-by":"publisher","unstructured":"L Hu, X Yin, Y Zhang, et al.  \"Blood.\"  137, \"Radiation-induced bystander effects impair transplanted human hematopoietic stem cells via oxidative DNA damage.\" 3339 (2021)","DOI":"10.1182\/blood.2020007362"},{"key":"10","doi-asserted-by":"publisher","unstructured":"X Song, X Hao, BT Zhu,  \"Free Radic Biol Med.\"  223, \"Role of mitochondrial reactive oxygen species in chemically-induced ferroptosis.\" 473 (2024)","DOI":"10.1016\/j.freeradbiomed.2024.07.006"},{"key":"11","doi-asserted-by":"publisher","unstructured":"C Andr\u00e9s Juan, JM P\u00e9rez de la Lastra, FJ Plou, et al.  \"Int J Mol Sci.\"  22, \"The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies.\" 4642 (2021)","DOI":"10.3390\/ijms22094642"},{"key":"12","doi-asserted-by":"publisher","unstructured":"I Lled\u00f3, B 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(2022)","DOI":"10.1186\/s10020-022-00503-7"},{"key":"17","doi-asserted-by":"publisher","unstructured":"T Uchiki, N Hamada, A Fujita, et al.  \"Sci Rep.\"  15, \"Mesenchymal stem cell implantation mitigates ionizing radiation-induced vascular damage in the murine aorta.\" 35708 (2025)","DOI":"10.1038\/s41598-025-19611-5"},{"key":"18","doi-asserted-by":"publisher","unstructured":"CJ Kurkjian, H Guo, ND Montgomery, et al.  \"Sci Rep.\"  7, \"The toll\u2013like Receptor 2\/6 agonist, FSL\u20131 lipopeptide, therapeutically mitigates acute radiation syndrome.\" 17355 (2017)","DOI":"10.1038\/s41598-017-17729-9"},{"key":"19","unstructured":"\"Medical Management of Radiation Accidents: Manual on the Acute Radiation Syndrome (METREPOL).\"  (2001)"},{"key":"20","doi-asserted-by":"publisher","unstructured":"IL Jackson, G Gurung, E Ayompe, et al.  \"Int J Radiat Biol.\"  97, \"Characterization of the hemorrhagic syndrome in the New Zealand white rabbit model following total body irradiation.\" S32 (2021)","DOI":"10.1080\/09553002.2020.1820601"},{"key":"22","doi-asserted-by":"publisher","unstructured":"DP O'Malley, YS Kim, SL Perkins, et al.  \"Mod Pathol.\"  18, \"Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders.\" 1550 (2005)","DOI":"10.1038\/modpathol.3800480"},{"key":"23","doi-asserted-by":"publisher","unstructured":"S Prakash, R Hoffman, S Barouk, et al.  \"lMod Patho.\"  25, \"Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition.\" 815 (2012)","DOI":"10.1038\/modpathol.2012.33"},{"key":"24","doi-asserted-by":"publisher","unstructured":"E Volinsky, A Lazmi-Hailu, N Cohen, et al.  \"Stem Cell Res Ther.\"  11, \"Alleviation of acute radiation-induced bone marrow failure in mice with human fetal placental stromal cell therapy.\" 337 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