Supramolecular ferric porphyrins and a cyclodextrin dimer as antidotes for cyanide poisoning
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- T Yamagiwa
- Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Isehara Kanagawa, Japan
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- AT Kawaguchi
- Department of Regenerative Medicine, Tokai University School of Medicine, Kanagawa, Japan
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- T Saito
- Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Isehara Kanagawa, Japan
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- S Inoue
- Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Isehara Kanagawa, Japan
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- S Morita
- Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Isehara Kanagawa, Japan
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- K Watanabe
- Department of Molecular Chemistry and Biochemistry, Doshisha University, Kyotanabe, Kyoto, Japan
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- H Kitagishi
- Department of Molecular Chemistry and Biochemistry, Doshisha University, Kyotanabe, Kyoto, Japan
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- K Koji
- Department of Molecular Chemistry and Biochemistry, Doshisha University, Kyotanabe, Kyoto, Japan
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- S Inokuchi
- Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Isehara Kanagawa, Japan
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説明
<jats:sec><jats:title>Objectives:</jats:title><jats:p> This study aimed to evaluate the antidotal effect of a newly developed supramolecular complex, ferric porphyrins and a cyclodextrin dimer (Fe<jats:sup>III</jats:sup>PIm3CD), that possess a higher binding constant and quicker binding rate to cyanide ions than those of hydroxocobalamin (OHCbl) in the presence of serum protein. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> First, in vitro cytochrome activity and cell viability were evaluated in murine fibroblast cells cultured with various doses of Fe<jats:sup>III</jats:sup>PIm3CD and potassium cyanide (KCN). Next, BALB/c mice were pretreated with intravenous OHCbl (0.23 mmol/kg), Fe<jats:sup>III</jats:sup>PIm3CD (0.23 mmol/kg), or saline and then received KCN (lethal dose 100% (LD<jats:sub>100</jats:sub>): 0.23 mmol/kg) through a stomach tube. Finally, as a resuscitation model, KCN-induced apnea was treated with a bolus injection of an equimolar dose of antidotes followed by a slow infusion of the same reagent. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Fe<jats:sup>III</jats:sup>PIm3CD showed dose-dependent antidotal effects in vitro. Pretreatment with Fe<jats:sup>III</jats:sup> PIm3CD prevented KCN-induced apnea significantly better than OHCbl. Resuscitation with Fe<jats:sup>III</jats:sup>PIm3CD resulted in an earlier resumption of respiration than that seen with OHCbl. However, 24-h survival was similar among the treatments (Fe<jats:sup>III</jats:sup>PIm3CD, nine of nine mice; OHCbl, eight of nine mice). </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Fe<jats:sup>III</jats:sup>PIm3CD exerted significant antidotal effects on cyanide toxicity in vitro and in vivo, with a potency equal in the mortality of cyanide-poisoned mice or superior in the respiratory status during an acute phase to those of OHCbl. </jats:p></jats:sec>
収録刊行物
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- Human & Experimental Toxicology
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Human & Experimental Toxicology 33 (4), 360-368, 2013-08-05
SAGE Publications