Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Int Immunopharmacol. 2013 Feb;15(2):348-56. doi: 10.1016/j.intimp.2012.12.029. Epub 2013 Jan 15.
The hematopoietic system is sensitive to radiation injury, and mortality can occur due to blood cell deficiency and stem cell loss. Genistein and the angiotensin converting enzyme (ACE) inhibitor captopril are two agents shown to protect the hematopoietic system from radiation injury. In this study we examined the combination of genistein with captopril for reduction of radiation-induced mortality from hematopoietic damage and the mechanisms of radiation protection. C57BL/6J mice were exposed to 8.25Gy (60)Co total body irradiation (TBI) to evaluate the effects of genistein and captopril alone and in combination on survival, blood cell recovery, hematopoietic progenitor cell recovery, DNA damage, and erythropoietin production. 8.25Gy TBI resulted in 0% survival after 30days in untreated mice. A single subcutaneous injection of genistein administered 24h before TBI resulted in 72% survival. Administration of captopril in the drinking water, from 1h through 30days postirradiation, increased survival to 55%. Genistein plus captopril increased survival to 95%. Enhanced survival was reflected in a reduction of radiation-induced anemia, improved recovery of nucleated bone marrow cells, splenocytes and circulating red blood cells. The drug combination enhanced early recovery of marrow progenitors: erythroid (CFU-E and BFU-E), and myeloid (CFU-GEMM, CFU-GM and CFU-M). Genistein alone and genistein plus captopril protected hematopoietic progenitor cells from radiation-induced micronuclei, while captopril had no effect. Captopril alone and genistein plus captopril, but not genistein alone, suppressed radiation-induced erythropoietin production. These data suggest that genistein and captopril protect the hematopoietic system from radiation injury via independent mechanisms.
造血系统对辐射损伤敏感，由于血细胞缺乏和干细胞丧失，可能导致死亡。染料木黄酮和血管紧张素转换酶（ACE）抑制剂卡托普利是两种已被证明可保护造血系统免受辐射损伤的药物。在这项研究中，我们研究了染料木黄酮与卡托普利联合使用以减少辐射引起的造血损伤导致的死亡率，以及辐射防护的机制。C57BL/6J 小鼠接受 8.25Gy（60）Co 全身照射（TBI），以评估染料木黄酮和卡托普利单独和联合使用对存活、血细胞恢复、造血祖细胞恢复、DNA 损伤和促红细胞生成素产生的影响。未经处理的小鼠在接受 8.25Gy TBI 后 30 天的存活率为 0%。在 TBI 前 24 小时给予一次皮下注射染料木黄酮可使存活率提高到 72%。在辐照后 1 小时至 30 天期间，通过饮用水给予卡托普利可将存活率提高到 55%。染料木黄酮加卡托普利将存活率提高到 95%。增强的存活率反映在减轻辐射引起的贫血、改善有核骨髓细胞、脾细胞和循环红细胞的恢复。药物联合使用增强了骨髓祖细胞的早期恢复：红系（CFU-E 和 BFU-E）和髓系（CFU-GEMM、CFU-GM 和 CFU-M）。染料木黄酮单独和染料木黄酮加卡托普利均可保护造血祖细胞免受辐射诱导的微核，而卡托普利则没有作用。卡托普利单独和染料木黄酮加卡托普利，而不是染料木黄酮单独，可抑制辐射诱导的促红细胞生成素产生。这些数据表明，染料木黄酮和卡托普利通过独立的机制保护造血系统免受辐射损伤。
