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

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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