Khan Shahanshah, Adhikari Jawahar Singh, Rizvi Moshahid Alam, Chaudhury Nabo Kumar
Division of Radiation Biodosimetry, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig. S. K. Mazumdar Marg, Timarpur, Delhi, 110054, India.
Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia-a Central University, Moulana Mohammad Ali Jauhar Marg, New Delhi, 110025, India.
Environ Toxicol. 2017 Feb;32(2):501-518. doi: 10.1002/tox.22254. Epub 2016 Mar 7.
Protection of hematopoietic, immunological, and gastrointestinal injuries from deleterious effects of ionizing radiation is prime rational for developing radioprotector. The objective of this study, therefore, was to evaluate the radioprotective potential of melatonin against damaging effects of radiation-induced hematopoietic, immunological, and gastrointestinal injuries in mice. C57BL/6 male mice were intraperitoneally administered with melatonin (50-150 mg/kg) 30 min prior to whole-body radiation exposure of 5 and 7.5 Gy using Co-teletherapy unit. Thirty-day survival against 7.5 Gy was monitored. Melatonin (100 mg/kg) pretreatment showed 100% survival against 7.5 Gy radiation dose. Melatonin pretreatment expanded femoral HPSCs, and inhibited spleenocyte DNA strands breaks and apoptosis in irradiated mice. At this time, it also protected radiation-induced loss of T cell sub-populations in spleen. In addition, melatonin pretreatment enhanced crypts regeneration and increased villi number and length in irradiated mice. Translocation of gut bacteria to spleen, liver and kidney were controlled in irradiated mice pretreated with melatonin. Radiation-induced gastrointestinal DNA strand breaks, lipid peroxidation, and expression of proapoptotic-p53, Bax, and antiapoptotic-Bcl-xL proteins were reversed in melatonin pretreated mice. This increase of Bcl-xL was associated with the decrease of Bax/Bcl-xL ratio. ABTS and DPPH radical assays revealed that melatonin treatment alleviated total antioxidant capacity in hematopoietic and gastrointestinal tissues. Present study demonstrated that melatonin pretreatment was able to prevent hematopoietic, immunological, and gastrointestinal radiation-induced injury, therefore, overcoming lethality in mice. These results suggest potential of melatonin in developing radioprotector for protection of bone marrow, spleen, and gastrointestine in planned radiation exposure scenarios including radiotherapy. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 501-518, 2017.
保护造血、免疫和胃肠道免受电离辐射的有害影响是开发辐射防护剂的主要理由。因此，本研究的目的是评估褪黑素对辐射诱导的小鼠造血、免疫和胃肠道损伤的辐射防护潜力。使用钴远距离治疗装置对C57BL/6雄性小鼠进行全身5 Gy和7.5 Gy辐射暴露前30分钟，腹腔注射褪黑素（50-150 mg/kg）。监测7.5 Gy辐射剂量下的30天存活率。褪黑素（100 mg/kg）预处理显示在7.5 Gy辐射剂量下存活率为100%。褪黑素预处理可扩增股骨造血干细胞，并抑制受辐照小鼠脾细胞DNA链断裂和凋亡。此时，它还能保护辐射诱导的脾脏中T细胞亚群的丢失。此外，褪黑素预处理可增强受辐照小鼠的隐窝再生，并增加绒毛数量和长度。用褪黑素预处理的受辐照小鼠可控制肠道细菌向脾脏、肝脏和肾脏的移位。在褪黑素预处理的小鼠中，辐射诱导的胃肠道DNA链断裂、脂质过氧化以及促凋亡蛋白p53、Bax和抗凋亡蛋白Bcl-xL的表达均得到逆转。Bcl-xL的增加与Bax/Bcl-xL比值的降低有关。ABTS和DPPH自由基测定表明，褪黑素处理可减轻造血和胃肠道组织中的总抗氧化能力。本研究表明，褪黑素预处理能够预防造血、免疫和胃肠道辐射诱导的损伤，从而克服小鼠的致死性。这些结果表明，褪黑素在开发辐射防护剂以保护包括放疗在内的计划辐射暴露场景中的骨髓、脾脏和胃肠道方面具有潜力。© 2016威利期刊公司。环境毒理学32: 501-518, 2017。
