کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5833050 | 1122617 | 2013 | 9 صفحه PDF | دانلود رایگان |
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 8.25Â Gy 60Co 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. 8.25Â Gy TBI resulted in 0% survival after 30Â days in untreated mice. A single subcutaneous injection of genistein administered 24Â h before TBI resulted in 72% survival. Administration of captopril in the drinking water, from 1Â h through 30Â days 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.
⺠We examined the effects of genistein with captopril on radiation injury in mice. ⺠We observed increased recovery of bone marrow cells, splenocytes and RBC. ⺠Genistein improved DNA repair in hematopoietic progenitors. ⺠Captopril reduced radiation-induced hypoxia. ⺠The two agents enhanced survival from radiation hematopoietic injury.
Journal: International Immunopharmacology - Volume 15, Issue 2, February 2013, Pages 348-356