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通过最小化自由基通量抑制辐射介导的细胞毒性:六角鬼臼亚组分对致死性电离辐射进行生物防护的可能机制之一。

Inhibition in radiation mediated cellular toxicity by minimizing free radical flux: one of the possible mechanisms of biological protection against lethal ionizing radiation by a sub- fraction of Podophyllum hexandrum.

作者信息

Gupta M L, Gupta V, Shukla S K, Verma S, Sankhwar S, Dutta A, Suri K A

机构信息

Institute of Nuclear Medicine and Allied Sciences, SK Mazumdar Marg, Timarpur, Delhi, India.

出版信息

Cell Mol Biol (Noisy-le-grand). 2010 Sep 11;56 Suppl:OL1341-9.

PMID:20937221
Abstract

The study has focused on exploring the mechanism of action of Podophyllum hexandrum sub-fraction (G-001M) exhibiting >90% protection in lethally irradiated mice. Currently, G-001M was assessed for antioxidant characteristics by evaluating DPPH, superoxide and hydrogen peroxide radical formation, anti-lipid per oxidation, metal chelation and total flavonoid content. To affirm cytoprotective efficacy of G-001M, plasmid DNA protection, blood WBC counts, marker for lipid peroxidation (MDA) and antioxidant status (GSH) in mice splenocytes and thymocytes were studied. G-001M, having high amount of total phenolic contents (200±10mg, w/w), exhibited dose dependent inhibition in DPPH and superoxide radical formation. Hydrogen peroxide radical scavenging was higher than standards. With pre-treatment of G-001M, plasmid DNA was also maximally restored to supercoiled form. Radiation modulated MDA and GSH values in splenocytes and thymocytes of mice altered significantly after 24 hrs and at later intervals, values were close to the controls. Radiation mediated losses in WBC counts were significantly regained (p<0.001) in G-001M pre-treated irradiated mice. The above findings explicitly conveyed that G-001M has successfully minimized radiation inflicted free radicals generation and their multiplication. This activity of G-001M could be undoubtedly among one of the major modes of action in extending whole body survival in lethally irradiated mice.

摘要

该研究聚焦于探索鬼臼(Podophyllum hexandrum)亚组分(G-001M)在致死性照射小鼠中展现出>90%保护作用的作用机制。目前,通过评估二苯基苦味酰基自由基(DPPH)、超氧阴离子和过氧化氢自由基的形成、抗脂质过氧化、金属螯合以及总黄酮含量来测定G-001M的抗氧化特性。为了确认G-001M的细胞保护功效,研究了小鼠脾细胞和胸腺细胞中的质粒DNA保护、血液白细胞计数、脂质过氧化标志物(丙二醛,MDA)和抗氧化状态(谷胱甘肽,GSH)。G-001M的总酚含量较高(200±10mg,w/w),在DPPH和超氧阴离子自由基形成方面表现出剂量依赖性抑制。其对过氧化氢自由基的清除能力高于标准品。经G-001M预处理后,质粒DNA也最大程度地恢复为超螺旋形式。照射后24小时,小鼠脾细胞和胸腺细胞中受辐射调节的MDA和GSH值发生显著变化,在随后的时间段内,这些值接近对照组。在经G-001M预处理的受照射小鼠中,辐射介导的白细胞计数损失得到显著恢复(p<0.001)。上述研究结果明确表明,G-001M成功地减少了辐射造成的自由基生成及其增殖。G-001M的这一活性无疑是其在延长致死性照射小鼠全身生存期方面的主要作用模式之一。

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