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

房屋火灾中CO和CN中毒特效解毒剂的研制

• 批准号: 23659749
• 负责人: KAWAGUCHI Akira
• 金额: $ 2.33万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659749/
• 关键词: 蘇生学; 家屋火災; 有毒ガス; 蘇生; 外呼吸; 内呼吸; 蘇生学; 家屋火災; 有毒ガス; 蘇生; 外呼吸; 内呼吸

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

在房屋火灾中，仍然有许多违反碳化碳（CO）和氢基因烯化（HCN）中毒的过早死亡的行为。 CO将紧密结合到血红蛋白以抑制外部呼吸和CN -ION（CN-）干扰细胞内线粒体电子转移级联反应以阻断内部呼吸。我们与Doshisha University合作开发了铁卟啉和环糊精二聚体的超分子复合物，作为CO（HemOCD）的特定解毒剂，以及CN-的解毒剂（Imidazolecyclodextrin：imcd）。在这项研究中，我们首先在体外评估了这些解毒剂，然后在动物实验中进行体内评估，以将其功能与传统解毒剂或盐水输注作为对照进行比较。在体外CN-毒性研究[1]，我们发现IMCD以剂量依赖性方式逆转了CN-毒性。尽管相等剂量的IMCD完全逆转了细胞色素活性和细胞活力方面的CN毒性，但与没有CN -CHALLENGER的对照细胞相比，羟羟胺（OHCBL）仅保护了80％的细胞色素活性。在体内，IMCD预处理显着降低了宿主内部kCN给药后呼吸暂停的发生率（IMCD 0/9，OHCBL 5/9，盐水9/9，P