Pathak Rupak, Kumar Vidya Prasanna, Hauer-Jensen Martin, Ghosh Sanchita Purohit
Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR.
Armed Forces Radiobiology Research Institute, USUHS, 4555 South Palmer Road Bldg 42, Bethesda, MD.
Mil Med. 2019 Mar 1;184(Suppl 1):644-651. doi: 10.1093/milmed/usy408.
Ionizing radiation exposure is a major concern for active military service members, as well as civilian population. Considering that the exposure is not predictable, it is imperative that strategies to counteract radiation damage must be discovered. Recent in vitro studies performed in our laboratory demonstrated that the vitamin E analog gamma-tocotrienol (GT3) in combination with cholesterol-lowering drugs (Statins), synergistically induced endothelial thrombomodulin, an anticoagulant with radio-protective efficacy. It was hypothesized that the combination of treatment with both GT3 along with Statins would provide better radiation protection in vivo than each drug individually. CD2F1 mice were injected subcutaneously with either vehicle or single dose of GT3 (200 mg/kg body weight) 24 hours before irradiation followed by oral or subcutaneous administration of various doses of simvastatin (25, 50, and 100 mg/kg body weight) before exposure to lethal doses (11.5 and 12 Gy) of Cobalt-60 (60Co) gamma-irradiation. The combined treatment group exhibited enhanced radiation lethality protection substantially, accelerated white blood cell recovery, and augmented restoration of bone marrow cellularity when compared to the animals treated with either drug exclusively. This information clearly suggests that combined treatment could be used as a safeguard for military personnel from exposure to harmful ionizing radiation.
电离辐射暴露是现役军人以及平民群体主要关注的问题。鉴于这种暴露是不可预测的，发现对抗辐射损伤的策略势在必行。我们实验室最近进行的体外研究表明，维生素E类似物γ-生育三烯酚（GT3）与降胆固醇药物（他汀类药物）联合使用，可协同诱导内皮血栓调节蛋白，这是一种具有放射防护功效的抗凝剂。据推测，GT3与他汀类药物联合治疗在体内提供的辐射防护效果要优于单独使用每种药物。在照射前24小时，给CD2F1小鼠皮下注射赋形剂或单剂量的GT3（200毫克/千克体重），然后在暴露于致死剂量（11.5和12戈瑞）的钴-60（60Co）γ射线照射之前，口服或皮下给予不同剂量的辛伐他汀（25、50和100毫克/千克体重）。与仅用一种药物治疗的动物相比，联合治疗组表现出显著增强的辐射致死性防护、加速的白细胞恢复以及骨髓细胞性的增强恢复。这一信息清楚地表明，联合治疗可作为军事人员免受有害电离辐射暴露的一种保障措施。
