Prophylactic efficacy of some chemoprotectants against abrin induced lethality.
Prophylactic efficacy of some chemoprotectants against abrin induced lethality.
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DOI：
10.2478/intox-2018-0013
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发表时间：
2018-08-01
影响因子：
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通讯作者：
Kaul, Ramesh Kumar
中科院分区：
文献类型：
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作者：
Saxena, Nandita;Bhutia, Yangchen Doma;Kaul, Ramesh Kumar
鸡骨草是鸡骨草产生的一种高毒性蛋白质。接触相思豆毒素，无论是通过事故还是恐怖主义行为，都对人类健康和安全构成重大风险。作为一种核糖体失活蛋白，它能使28 S rRNA脱嘌呤并抑制蛋白质合成。它是一种强力的毒素战剂。相思豆毒素中毒没有解毒剂。支持性护理是治疗相思豆毒素暴露的唯一选择。通过开展暴露前和暴露后治疗来制定相思子毒素对策变得越来越重要。本研究的目的是筛选某些药物化合物的化学保护特性，对相思豆毒素在BALB/c雄性小鼠体内的毒性。筛选了21种具有抗氧化、抗炎和细胞保护特性或它们的组合的化合物，并作为1小时预处理给药，然后暴露于致死剂量（2* LD 50，腹膜内）的相思豆毒素。为了评估化合物的保护功效，监测存活率和体重。与相思豆毒素相比，15种化合物显著延长了动物的存活时间。这些化合物中的以下五种，即：表儿茶素-3-没食子酸酯、没食子酸、硫辛酸、GSH和吲哚美辛延长了6至9天的寿命。这些化合物还减弱了相思豆毒素诱导的炎症和与肝功能相关的酶，但它们都不能阻止相思豆毒素诱导的致死性。提供寿命延长的化合物可用于为其他支持性治疗提供时间窗，并且还可用作与其他医学对策一起对抗相思豆毒素诱导的致死性的组合疗法。
Abrin is a highly toxic protein produced by Abrus precatorius. Exposure to abrin, either through accident or by act of terrorism, poses a significant risk to human health and safety. Abrin functions as a ribosome-inactivating protein by depurinating the 28S rRNA and inhibits protein synthesis. It is a potent toxin warfare agent. There are no antidotes available for abrin intoxication. Supportive care is the only option for treatment of abrin exposure. It is becoming increasingly important to develop countermeasures for abrin by developing pre- and post-exposure therapy. The aim of this study is to screen certain pharmaceutical compounds for their chemoprotective properties against abrin toxicity in vivo in BALB/c male mice. Twenty-one compounds having either antioxidant, anti-inflammatory and cyto-protective properties or combination of them, were screened and administered as 1h pre-treatment followed by exposure of lethal dose (2*LD50, intraperitoneally) of abrin. To assess the protective efficacy of the compounds, survival and body weight was monitored. Fifteen compounds extended the survival time of animals significantly, as compared to abrin. The following five of these compounds, namely: Epicatechin-3-gallate, Gallic Acid, Lipoic Acid, GSH and Indomethacin extended the life time ranging from 6 to 9 days. These compounds also attenuated the abrin induced inflammation and enzymes associated with liver function, but none of them could prevent abrin induced lethality. The compounds offering extension of life could be useful to provide a time-window for other supportive treatment and could also be used as combinatorial therapy with other medical countermeasures against abrin induced lethality.