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A combined prophylactic modality of podophyllotoxin and rutin alleviates radiation induced injuries to the lymphohematopoietic system of mice by modulating cytokines, cell cycle progression, and apoptosis.
Free Radical Research ( IF 3.6 ) Pub Date : 2020-08-11 , DOI: 10.1080/10715762.2020.1805447
Savita Verma 1 , Manju Lata Gupta 2 , Kamal Kumar 1
Affiliation  

The present study was conceptualized to delineate radioprotective efficacy of a formulation G-003M (a combination of podophyllotoxin and rutin) against radiation-induced damage to the lymphohematopoietic system of mice. C57BL/6J mice, treated with G-003M 1 h prior to 9 Gy lethal dose, were assessed for reactive oxygen species (ROS)/nitric oxide (NO) generation, antioxidant alterations, Annexin V/PI and TUNEL staining for apoptosis, modulation of apoptotic proteins, cell proliferation, histological alterations in thymus and cell cycle arrest in bone marrow cells. Induction of granulocyte colony-stimulating factor (G-CSF), granulocytes macrophage colony-stimulating factor (GM-CSF), interleukin-IL-6, IL-10, IL-1α, and IL-1β in response to G-003M was also evaluated in different groups of mice. Haematopoietic reconstitution with G-003M was explored by examining endogenous spleen colony-forming units (CFU-S) in irradiated animals. G-003M significantly inhibited ROS/NO, malondialdehyde (MDA) and restored cellular antioxidant glutathione in the thymus of irradiated animals. G-003M pre-treatment significantly (p < 0.001) restrained apoptosis in thymocytes via upregulation of Bcl2 and down-regulation of Bax, p53 and caspase-3. Stimulation of cell proliferation and inhibition of apoptosis by G-003M, restored architecture of thymus in irradiated animals within 30 days as evaluated by histological analysis. G-003M arrested cells at the G2/M phase by inducing reversible cell cycle arrest. Peak expression of G-CSF (45-fold) and IL-6 (60-fold) as well as moderate induction of GM-CSF, IL-10, IL-1α by G-003M helped in haematopoietic recovery of irradiated mice. A higher number of endogenous CFU-S in G-003M pre-treated irradiated mice suggested haematopoietic recovery. Data obtained from the current study affirms that G-003M can be proved as a potential radioprotective agent against radiation damage.



中文翻译:

鬼臼毒素和芦丁的联合预防方式可通过调节细胞因子,细胞周期进程和凋亡来减轻放射线对小鼠淋巴造血系统的伤害。

本研究被概念化以描绘制剂G-003M(鬼臼毒素和芦丁的组合)对辐射诱导的小鼠淋巴造血系统损伤的放射防护功效。评估在9 Gy致死剂量前1小时用G-003M处理的C57BL / 6J小鼠的活性氧(ROS)/一氧化氮(NO)生成,抗氧化剂改变,膜联蛋白V / PI和TUNEL染色的凋亡,调节作用凋亡蛋白,细胞增殖,胸腺组织学改变以及骨髓细胞的细胞周期停滞。响应G-003M,诱导了粒细胞集落刺激因子(G-CSF),粒细胞巨噬细胞集落刺激因子(GM-CSF),白介素-IL-6,IL-10,IL-1α和IL-1β的诱导。还评估了不同组的小鼠。通过检查受辐照动物的内源性脾集落形成单位(CFU-S),探索了用G-003M进行的造血重建。G-003M显着抑制辐照动物胸腺中的ROS / NO,丙二醛(MDA)并恢复细胞抗氧化剂谷胱甘肽。G-003M预处理明显(p  <0.001)通过Bcl2的上调和Bax,p53和caspase-3的下调来抑制胸腺细胞凋亡。通过组织学分析评估,G-003M刺激细胞增殖并抑制细胞凋亡,在30天内恢复了辐射动物胸腺的结构。G-003M通过诱导可逆的细胞周期阻滞将细胞阻滞在G2 / M期。G-003M的G-CSF(45倍)和IL-6(60倍)的高峰表达以及G-003M对GM-CSF,IL-10,IL-1α的中等诱导有助于辐射小鼠的造血恢复。在G-003M预处理的辐射小鼠中,较高数量的内源性CFU-S提示造血功能恢复。从当前研究获得的数据证实,G-003M可以被证明是潜在的抗辐射损伤的辐射防护剂。

更新日期:2020-09-21
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