Division of Radiation Biodosimetry, Institute of Nuclear Medicine and Allied Sciences (INMAS)-Defence Research and Development Organisation (DRDO), Brig. SK Mazumdar Marg, Timarpur, Delhi 110054, India.
Division of Radiation Biodosimetry, Institute of Nuclear Medicine and Allied Sciences (INMAS)-Defence Research and Development Organisation (DRDO), Brig. SK Mazumdar Marg, Timarpur, Delhi 110054, India; Department of Pharmacology, School of Pharmaceutical Education and Research, Hamdard University, Hamdard nagar, New Delhi 110062, India.
Life Sci. 2022 Jan 15;289:120190. doi: 10.1016/j.lfs.2021.120190. Epub 2021 Dec 6.
Hematopoietic acute radiation syndrome (H-ARS) can cause lethality, and therefore, the necessity of a safe radioprotector. The present study was focused on investigating the role of melatonin in granulocytes colony-stimulating factor (G-CSF) and related mechanisms underlying the reduction of DNA damage in hematopoietic system of irradiated mice.
C57BL/6 male mice were exposed to 2, 5, and 7.5Gy of whole-body irradiation (WBI), 30 min after intra-peritoneal administration of melatonin with different doses. Mice were sacrificed at different time intervals after WBI, and bone marrow, splenocytes, and peripheral blood lymphocytes were isolated for studying various parameters including micronuclei (MN), cell cycle, comet, γ-H2AX, gene expression, amino acid profiling, and hematology.
Melatonin100mg/kg ameliorated radiation (7.5Gy and 5Gy) induced MN frequency and cell death in bone marrow without mortality. At 24 h of post-WBI (2Gy), the frequency of micronucleated polychromatic erythrocytes (mnPCE) with different melatonin doses revealed 20 mg/kg as optimal i.p. dose for protecting the hematopoietic system against radiation injury. In comet assay, a significant reduction in radiation-induced % DNA tail (p ≤ 0.05) was observed at this dose. Melatonin reduced γ-H2AX foci/cell and eventually reached to the control level. Melatonin also decreased blood arginine levels in mice after 24 h of WBI. The gene expression of G-CSF, Bcl-2-associated X protein (BAX), and Bcl2 indicated the role of melatonin in G-CSF regulation and downstream pro-survival pathways along with anti-apoptotic activity.
The results revealed that melatonin recovers the hematopoietic system of irradiated mice by inducing G-CSF mediated radioprotection.
造血急性辐射综合征（H-ARS）可导致死亡，因此需要安全的辐射防护剂。本研究旨在研究褪黑素在粒细胞集落刺激因子（G-CSF）中的作用及其在减少照射小鼠造血系统 DNA 损伤中的相关机制。
C57BL/6 雄性小鼠在接受 2、5 和 7.5Gy 全身照射（WBI）后 30 分钟，经腹腔给予不同剂量的褪黑素。WBI 后不同时间间隔处死小鼠，分离骨髓、脾细胞和外周血淋巴细胞，研究各种参数，包括微核（MN）、细胞周期、彗星、γ-H2AX、基因表达、氨基酸谱和血液学。
褪黑素 100mg/kg 可改善骨髓中由辐射（7.5Gy 和 5Gy）引起的 MN 频率和细胞死亡，而不引起死亡率。在 WBI 后 24 小时（2Gy），用不同褪黑素剂量检测的多色性红细胞中的微核率（mnPCE）显示 20mg/kg 是保护造血系统免受辐射损伤的最佳腹腔内剂量。在彗星试验中，在该剂量下观察到辐射诱导的%DNA 尾（p≤0.05）显著减少。褪黑素减少了 γ-H2AX 焦点/细胞，最终达到对照水平。褪黑素还降低了 WBI 后 24 小时小鼠血液中的精氨酸水平。G-CSF、Bcl-2 相关 X 蛋白（BAX）和 Bcl2 的基因表达表明褪黑素在 G-CSF 调节及其下游抗凋亡活性中的作用。
结果表明，褪黑素通过诱导 G-CSF 介导的辐射防护作用，恢复照射小鼠的造血系统。
