Singh Vijay K, Fatanmi Oluseyi O, Wise Stephen Y, Carpenter Alana, Nakamura-Peek Sara, Serebrenik Artur A, Kaytor Michael D
Department of Pharmacology and Molecular Therapeutics, Division of Radioprotectants, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Int J Radiat Biol. 2022;98(5):958-967. doi: 10.1080/09553002.2021.1981556. Epub 2021 Sep 28.
Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome (H-ARS) and delayed effects of acute radiation exposure (DEARE). There is no radiation medical countermeasure (MCM) approved by the U.S. Food and Drug Administration which can be used prior to radiation exposure to protect exposed individuals. Different formulations containing synthetic genistein (BIO 300) are being developed to counter the harmful effects of radiation exposure.
We investigated the efficacy of a BIO 300 oral powder (OP) formulation as a prophylactic radiation MCM against a lethal dose of cobalt-60 gamma-radiation in CD2F1 male mice while comparing to other formulations of BIO 300 and Neulasta (PEGylated filgrastim), a standard of care drug for H-ARS.
BIO 300 OP provided significant radioprotection against ionizing radiation in mice when administered twice per day for six days prior to total-body radiation exposure. Its radioprotective efficacy in the murine model was comparable to the efficacy of a single subcutaneous () injection of Neulasta administered after total-body radiation exposure.
Our results demonstrate that BIO 300 OP, which can be administered orally, is a promising prophylactic radiation countermeasure for H-ARS.
暴露于高剂量电离辐射可导致造血急性放射综合征（H-ARS）和急性辐射暴露的延迟效应（DEARE）。美国食品药品监督管理局尚未批准任何可在辐射暴露前用于保护受照个体的辐射医学对策（MCM）。目前正在研发不同配方的合成染料木黄酮（BIO 300），以对抗辐射暴露的有害影响。
我们研究了BIO 300口服粉剂（OP）配方作为预防性辐射MCM对CD2F1雄性小鼠致死剂量的钴-60γ辐射的疗效，同时与BIO 300的其他配方以及H-ARS的标准护理药物Neulasta（聚乙二醇化非格司亭）进行比较。
在全身辐射暴露前连续六天每天两次给予BIO 300 OP时，其对小鼠电离辐射具有显著的辐射防护作用。其在小鼠模型中的辐射防护效果与全身辐射暴露后单次皮下注射Neulasta的效果相当。
我们的结果表明，可口服的BIO 300 OP是一种有前景的针对H-ARS的预防性辐射对策。
