Landauer Michael R, Srinivasan Venkataraman, Seed Thomas M
Radiation Casualty Management Team, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA.
J Appl Toxicol. 2003 Nov-Dec;23(6):379-85. doi: 10.1002/jat.904.
The radioprotective and behavioral effects of an acute administration of the isoflavone genistein (4',5,7-trihydroxyflavone) were investigated in adult CD2F1 male mice. Mice were administered a single subcutaneous (s.c.) dose of genistein either 24 h or 1 h before a lethal dose of gamma radiation (9.5-Gy of cobalt-60 at 0.6 Gy min(-1)). Mice received saline, PEG-400 vehicle or genistein at 3.125, 6.25, 12.5, 25, 50, 100, 200, or 400 mg kg(-1) body weight. For mice treated 24 h before irradiation there was a significant increase in 30-day survival for animals receiving genistein doses of 25 to 400 mg kg(-1) (p<0.001). In contrast, the 30-day survival rates of mice treated with genistein 1 h before irradiation were not significantly different from those of the vehicle control group. Additionally, the acute toxicity of genistein was evaluated in non-irradiated male mice administered a single s.c. injection of saline, vehicle, or genistein at 100, 200 or 400 mg kg(-1). At these genistein doses there were no adverse effects, compared with controls, on locomotor activity, grip strength, motor coordination, body weight, testes weight, or histopathology. These results demonstrate that a single s.c. administration of the flavonoid genistein at non-toxic doses provides protection against acute radiation injury.
研究了急性给予异黄酮染料木黄酮（4'，5，7 - 三羟基黄酮）对成年CD2F1雄性小鼠的辐射防护作用和行为影响。在给予致死剂量的γ射线（钴 - 60，9.5 Gy，剂量率0.6 Gy min⁻¹）照射前24小时或1小时，给小鼠单次皮下注射染料木黄酮。小鼠接受生理盐水、聚乙二醇 - 400载体或剂量为3.125、6.25、12.5、25、50、100、200或400 mg kg⁻¹体重的染料木黄酮。对于在照射前24小时接受治疗的小鼠，接受25至400 mg kg⁻¹染料木黄酮剂量的动物30天存活率显著增加（p < 0.001）。相比之下，在照射前1小时用染料木黄酮治疗的小鼠的30天存活率与载体对照组没有显著差异。此外，在未照射的雄性小鼠中评估了染料木黄酮的急性毒性，这些小鼠单次皮下注射生理盐水、载体或剂量为100、200或400 mg kg⁻¹的染料木黄酮。与对照组相比，在这些染料木黄酮剂量下，对运动活性、握力、运动协调性、体重、睾丸重量或组织病理学没有不良影响。这些结果表明，以无毒剂量单次皮下给予类黄酮染料木黄酮可提供对急性辐射损伤的保护。
