Radiation protection effect and its mechanism of multiple nilestriol administrations on the mice with bone marrow type of acute radiation syndrome

Objective To understand the radiation protection effect of pre-irradiation administrations of nilestriol on the mice with bone marrow type of acute radiation syndrome after irradiation with 60Co γ-rays, along with its mechanisms for improvement of hematopoiesis. Methods The nilestriol administration protocols were prepared by analysis of peripheral blood cell counts and survival rate experiment on mice. The mechanisms by which the pre-irradiation twice administrations improved the post-irradiation recovery of bone marrow hematopoiesis were studied by the analysis of the surface marker of bone marrow hematopoietic stem/progenitor cells of mice and by the inspection of hematopoietic progenitor cell colony and by using histopathological assessment of bone marrow. Results Pre-irradiation administration of nilestriol at two-or three-day intervals had been shown to increase survival rates up to 100% in mice exposed to 9.0 Gy γ-rays, which was superior to a single administration (20%, χ2=21.66, 21.66, P<0.05). The pre-irradiation administration both at one-day or two-day intervals were capable of improving the recovery of peripheral blood counts, including white blood cell (WBC), red blood cell (RBC), and platelet in mice exposed to 6.5 Gy (F=21.33, 100.9, 49.34, 19.19, P <0.05), showing the better effects than a single administration (F=17.11, 63.38, 21.89, 14.37, P<0.05). The two-day-interval administration of nilestriol could significantly increase the numbers of bone marrow hematopoietic stem/progenitor cell counts (t=8.58, 2.80, P<0.05) in mice on day 10 after 6.5 Gy irradiation. This also could be capable to significantly improve colony formation, with there being statistical difference compared with single administration(t=4.29, 6.34, P<0.05). Also the administration at two-day-interval were also usefull in reconstruction of hematopoietic cell hyperplasia of bone marrow of irradiated mice. Conclusions As compared with conventional single admination, the pre-irradiation multiple administrations of nilestriol showed significantly improved radiation protection effects. Considering a nuclear medical emergency rescue, it is recommended to follow the pre-irradiation administration of nilestriol at two-day interval, which could obtain the best protection effects at minimum administration frequency. Key words: Nilestriol; Bone marrow type acute radiation syndrome; Radioprotection; Hematopoietic stem cells