The Vitamin B12 Analog Cobinamide Is an Effective Antidote for Oral Cyanide Poisoning
The Vitamin B12 Analog Cobinamide Is an Effective Antidote for Oral Cyanide Poisoning
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DOI：
10.1007/s13181-016-0566-4
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发表时间：
2016-12-01
影响因子：
2.9
通讯作者：
Brenner, Matthew
中科院分区：
文献类型：
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作者：
Lee, Jangwoen;Mahon, Sari B.;Brenner, Matthew
氰化物是一种主要的化学威胁，与吸入相比，摄入氰化物具有更高的超致死剂量暴露风险，但由于治疗窗口较长，并且胃肠道氰化物储库可以在全身吸收之前被中和，因此提供了有效治疗的机会。我们假设，口服给药的可宾胺可能作为一个高结合亲和力的清除剂，胃碱化将减少氰化物的吸收，同时增加可宾胺的结合，进一步提高解毒effictiveness.Methods新西兰白色兔30只分为5组，并给予口服氰化物中毒（50 mg）的致死剂量。动物的存活时间通过单独口服氰化物、口服氰化物与口服碳酸氢钠缓冲液（500 mg）胃碱化以及与含水羟钴胺或二硝基钴胺（250 mM）联合监测。红细胞氰化物浓度，血浆cobinamide，和硫氰酸盐浓度测定从血液samples.Results在氰化物摄入的动物，口服碳酸氢钠单独显着延长生存时间为20.3 +/- 8.6分钟相比，10.5 +/- 4.3分钟，在盐水处理的控制，但没有导致总生存。Aquohydroxocobinamide和dinitrocobinamide分别将存活时间延长至64 +/- 41（p < 0.05）和75 +/- 16.4 min（p < 0.001）。与水羟钴胺相比，二硝基钴胺表现出更大的全身吸收和降低血压。二硝基氨也显着增加红细胞氰化物浓度。在所有条件下，血浆硫氰酸盐浓度逐渐增加，随着时间的推移。结论这项研究表明，一个有前途的新方法来治疗高剂量的氰化物摄入，单独与胃碱化，并结合口服可宾胺治疗超致死剂量的口服氰化物在兔。
Introduction Cyanide is a major chemical threat, and cyanide ingestion carries a higher risk for a supra-lethal dose exposure compared to inhalation but provides an opportunity for effective treatment due to a longer treatment window and a gastrointestinal cyanide reservoir that could be neutralized prior to systemic absorption. We hypothesized that orally administered cobinamide may function as a high-binding affinity scavenger and that gastric alkalinization would reduce cyanide absorption and concurrently increase cobinamide binding, further enhancing antidote effectiveness.Methods Thirty New Zealand white rabbits were divided into five groups and were given a lethal dose of oral cyanide poisoning (50 mg). The survival time of animals was monitored with oral cyanide alone, oral cyanide with gastric alkalinization with oral sodium bicarbonate buffer (500 mg), and in combination with either aquohydroxocobinamide or dinitrocobinamide (250mM). Red blood cell cyanide concentration, plasma cobinamide, and thiocyanate concentrations were measured from blood samples.Results In cyanide ingested animals, oral sodium bicarbonate alone significantly prolonged survival time to 20.3 +/- 8.6 min compared to 10.5 +/- 4.3 min in saline-treated controls, but did not lead to overall survival. Aquohydroxocobinamide and dinitrocobinamide increased survival time to 64 +/- 41 (p < 0.05) and 75 +/- 16.4 min (p < 0.001), respectively. Compared to aquohydroxocobinamide, dinitrocobinamide showed greater systemic absorption and reduced blood pressure. Dinitrocobinamide also markedly increased the red blood cell cyanide concentration. Under all conditions, the plasma thiocyanate concentration gradually increased with time.Conclusion This study demonstrates a promising new approach to treat high-dose cyanide ingestion, with gastric alkalinization alone and in combination with oral cobinamide for treating a supra-lethal dose of orally administered cyanide in rabbits.