Tiwari Mrinalini, Dixit Bhakti, Parvez Suhel, Agrawala Paban K
Radiation Genetics and Epigenetics Department, Institute of Nuclear Medicine and Allied Sciences, Delhi 110 054, India.
Department of Toxicology, Jamia Hamdard University, New Delhi, 110062, India.
Biomed Pharmacother. 2017 Apr;88:203-209. doi: 10.1016/j.biopha.2016.12.129. Epub 2017 Jan 17.
Agents capable of providing protection, mitigation or therapy against radiation injuries have long been of interest of radiation biologists owing to the ever expanding application of radiation in our day to day life despite the well reported ill effects of exposure. The current study investigates radiomitigating potential of EGCG (epigallocatechin gallate), a tea polyphenol with known DNMT inhibitory property, in C57 Bl/6 mice model. Treatment with 0.1833mg/kg body weight EGCG, 1.5h post-irradiation to lethally whole body irradiated mice rendered 45% survival for 30days and also helped restoring the body weight of the animals. An early recovery of various hematological parameters was observed in EGCG treated animals compared to radiation alone group. Significant recovery in the number of bone marrow colony forming cells was observed in EGCG treated irradiated animals. EGCG reduced cytogenetic damage to bone marrow cells in radiation exposed mice significantly as studied by micronucleus assay without any significant affect on cell cycle distribution of the bone marrow cells. ELISA assay with bone marrow cell lysates showed EGCG as an inhibitor of HDAC activity and DNase accessibility assay showed EGCG treatment increased the accessibility of chromatin to the enzyme. The results suggest EGCG provides mitigation against radiation injury to the hemopoietic system of mice and also inhibits HDAC enzyme activity. However, further studies are required to understand its mechanism of action.
尽管辐射暴露的不良影响已被充分报道,但由于辐射在我们日常生活中的应用不断扩大,能够提供针对辐射损伤的防护、缓解或治疗作用的物质长期以来一直是辐射生物学家关注的焦点。当前的研究在C57 Bl/6小鼠模型中调查了表没食子儿茶素没食子酸酯(EGCG)的辐射缓解潜力,EGCG是一种具有已知DNA甲基转移酶抑制特性的茶多酚。对致死性全身照射的小鼠在照射后1.5小时给予0.1833mg/kg体重的EGCG治疗,使30天的存活率达到45%,并且还有助于恢复动物的体重。与仅接受辐射的组相比,在接受EGCG治疗的动物中观察到各种血液学参数的早期恢复。在接受EGCG治疗的照射动物中观察到骨髓集落形成细胞数量有显著恢复。通过微核试验研究发现,EGCG显著降低了辐射暴露小鼠骨髓细胞的细胞遗传学损伤,且对骨髓细胞的细胞周期分布没有任何显著影响。用骨髓细胞裂解物进行的ELISA分析表明EGCG是HDAC活性的抑制剂,DNA酶可及性分析表明EGCG处理增加了染色质对该酶的可及性。结果表明EGCG可减轻小鼠造血系统的辐射损伤,并且还抑制HDAC酶活性。然而,需要进一步研究以了解其作用机制。