Monitoring Dose Response of Cyanide Antidote Dimethyl Trisulfide in Rabbits Using Diffuse Optical Spectroscopy.
Monitoring Dose Response of Cyanide Antidote Dimethyl Trisulfide in Rabbits Using Diffuse Optical Spectroscopy.
复制标题
使用漫反射光谱法监测兔体内氰化物解毒剂二甲基三硫醚的剂量反应。
DOI：
10.1007/s13181-018-0680-6
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Brenner,Matthew
中科院分区：
文献类型：
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作者：
Lee,Jangwoen;Rockwood,Gary;Logue,Brian;Manandhar,Erica;Petrikovics,Ilona;Han,Changhoon;Bebarta,Vik;Mahon,SariB;Burney,Tanya;Brenner,Matthew
氰化物(CN)中毒是一种因意外或故意接触而造成的严重化学威胁。目前的CN暴露治疗方法，包括直接结合剂、高铁血红蛋白供体和硫磺供体，都有几个局限性。二甲基三硫醚(DMTS)能与CN反应生成毒性较低的硫氰酸盐，即使没有硫转移酶的存在也能高效地生成。我们研究了一种可溶的DMTS配方，它有可能为CN解毒提供连续的底物供应，这种底物可以在大规模伤亡情况下通过肌肉注射(IM)输送。我们还使用了非侵入性技术，漫反射光谱(DOS)，以监测与CN暴露和逆转相关的生理变化。方法新西兰大白兔36只，注入致死剂量的氰化钠溶液(20 mg/60 mg生理盐水)。动物被分成三组，分别肌肉注射生理盐水、低剂量(20 Mg)和高剂量(150 Mg)DMTs。在整个实验过程中，DOS不断评估组织中血红蛋白浓度和细胞色素C氧化酶氧化还原状态的变化。结果肌注DMTS增加了致死性CN中毒的存活率。DOS显示大剂量DMTs(150 Mg)可逆转CN暴露对细胞色素c氧化酶的影响，而低剂量DMTs(20 Mg)并不能完全逆转这种效应，即使在存活的动物中也是如此。结论本研究在中等体型动物模型上证明了通过肌肉注射为非罗丹明介导的硫转移酶途径提供底物的新方法的潜在有效性，并表明DOS可用于优化DMTs的治疗。
IntroductionCyanide (CN) poisoning is a serious chemical threat from accidental or intentional exposures. Current CN exposure treatments, including direct binding agents, methemoglobin donors, and sulfur donors, have several limitations. Dimethyl trisulfide (DMTS) is capable of reacting with CN to form the less toxic thiocyanate with high efficiency, even without the sulfurtransferase rhodanese. We investigated a soluble DMTS formulation with the potential to provide a continuous supply of substrate for CN detoxification which could be delivered via intramuscular (IM) injection in a mass casualty situation. We also used non-invasive technology, diffuse optical spectroscopy (DOS), to monitor physiologic changes associated with CN exposure and reversal.MethodsThirty-six New Zealand white rabbits were infused with a lethal dose of sodium cyanide solution (20 mg/60 ml normal saline). Animals were divided into three groups and treated with saline, low dose (20 mg), or high dose (150 mg) of DMTS intramuscularly. DOS continuously assessed changes in tissue hemoglobin concentrations and cytochrome c oxidase redox state status throughout the experiment.ResultsIM injection of DMTS increased the survival in lethal CN poisoning. DOS demonstrated that high-dose DMTS (150 mg) reversed the effects of CN exposure on cytochrome c oxidase, while low dose (20 mg) did not fully reverse effects, even in surviving animals.ConclusionsThis study demonstrated potential efficacy for the novel approach of supplying substrate for non-rhodanese mediated sulfur transferase pathways for CN detoxification via intramuscular injection in a moderate size animal model and showed that DOS was useful for optimizing the DMTS treatment.