Development of Specific Antidotes for CO and CN Poisoning in House Fire

在住宅火灾中，因一氧化碳（CO）和氢氰酸（HCN）中毒而过早死亡的受害者仍为数不少。CO与血红蛋白紧密结合以抑制外呼吸，CN-离子（CN-）干扰细胞内线粒体电子传递级联以阻止内呼吸。我们与同志社大学合作开发铁卟啉和环糊精二聚体的超分子复合物，作为CO（Hemocyclodextrin：HemoCD）的特异性解毒剂以及CN-（Imidazolecyclodextrin：ImCD）的解毒剂。在本研究中，我们首先在体外评估这些解毒剂，然后在动物实验中在体内比较它们与传统解毒剂或生理盐水输注作为对照的功能。在体外CN毒性研究中[1]，我们发现ImCD以剂量依赖性方式逆转CN毒性;而等摩尔剂量的ImCD在细胞色素活性和细胞活力方面完全逆转CN毒性，与未进行CN攻击的对照细胞相比，羟钴胺（OHCbl）仅保护80%的细胞色素活性。在体内，ImCD预处理显著降低了胃内给予KCN后呼吸暂停的发生率（ImCD 0/9，OHCbl 5/9，生理盐水9/9，P

There still are numerous victims of premature death from carbon-monoxide (CO) and hydrogen-cyanide (HCN) poisoning in house fire. CO combines tightly to hemoglobin to inhibit outer respiration and CN‐ion (CN‐) interferes intracellular mitochondrial electron transfer cascade to block inner respiration. We collaborate with Doshisha University to develop supramolecular complex of iron porphylin and cyclodextrin dimer as a specific antidote for CO (Hemocyclodextrin: HemoCD) as well as an antidote for CN‐(Imidazolecyclodextrin: ImCD). In this study, we evaluate these antidotes first in vitro and then in vivo in animal experiments to compare their function with traditional antidotes or saline infusion as the control. In in vitro CN‐toxicity studies [1], we found that ImCD reverse the CN‐toxicity in a dose dependent manner; while an equimolar dose of ImCD completely reversed the CN‐toxicity in terms of cytochrome activity and cell viability, hydroxocobalamine (OHCbl) protected only 80% of the cytochrome activity compared with the control cells without CN‐challenge. In in vivo, ImCD pretreatment significantly reduced the incidence of apnea after intra-gastric KCN administration (ImCD 0/9, OHCbl 5/9, Saline 9/9, P