Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Majumdar Marg, Timarpur, New Delhi 110054, India.
Evid Based Complement Alternat Med. 2011;2011:175140. doi: 10.1093/ecam/nep061. Epub 2011 Feb 13.
This study aims at the development of a safe and effective formulation to counter the effects of lethal irradiation. The sub-fraction (G-001M), prepared from Podophyllum hexandrum has rendered high degree of survival (>90%) at a dose of 6 mg kg(-1) body weight (intramuscular) in lethally irradiated mice. Therapeutic dose of G-001M, at about 20 times lower concentration than its LD(100), has revealed a DRF of 1.62. Comet assay studies in peripheral blood leukocytes have reflected that, treatment of G-001M before irradiation has significantly reduced DNA tail length (P < .001) and DNA damage score (P < .001), as compared to radiation-only group. Spleen cell counts in irradiated animals had declined drastically at the very first day of exposure, and the fall continued till the 5th day (P < .001). In the treated irradiated groups, there was a steep reduction in the counts initially, but this phase did not prolong. More than 60% decline in thymocytes of irradiated group animals was registered at 5 h of irradiation when compared with controls, and the fall progressed further downwards with the similar pace till 5th day of exposure (P < .001). At later intervals, thymus was found fully regressed. In G-001M pre-treated irradiated groups also, thymocytes decreased till the 5th day but thereafter rejuvenated and within 30 days of treatment the values were close to normal. Current studies have explicitly indicated that, G-001M in very small doses has not only rendered high survivability in lethally irradiated mice, but also protected their cellular DNA, besides supporting fast replenishment of the immune system.
本研究旨在开发一种安全有效的制剂以对抗致死性辐射的影响。从 Podophyllum hexandrum 中制备的亚馏分 (G-001M),在 6mg/kg(-1)体重(肌肉内)的致死剂量照射的小鼠中,存活率高达 90%以上。G-001M 的治疗剂量,约为其 LD(100)的 20 倍,其 DRF 为 1.62。外周血白细胞的彗星试验研究表明,与仅辐射组相比,G-001M 在照射前的处理显著降低了 DNA 尾长 (P <.001) 和 DNA 损伤评分 (P <.001)。照射动物的脾细胞计数在暴露的第一天急剧下降,并且下降持续到第 5 天 (P <.001)。在接受治疗的照射组中,计数最初急剧下降,但这一阶段没有延长。与对照组相比,照射组动物的胸腺细胞在 5 小时照射时下降了 60%以上,并且随着时间的推移,下降速度进一步加快,直到第 5 天(P <.001)。在随后的时间间隔中,发现胸腺完全退化。在 G-001M 预处理的照射组中,胸腺细胞也减少到第 5 天,但随后恢复活力,在 30 天的治疗后,数值接近正常。目前的研究明确表明,G-001M 在非常小的剂量下不仅使致死性照射的小鼠具有高存活率,而且保护了其细胞 DNA,同时支持免疫系统的快速补充。