論文 - 詳細
RRC ID | 44572 |
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著者 | Yamagiwa T, Kawaguchi AT, Saito T, Inoue S, Morita S, Watanabe K, Kitagishi H, Koji K, Inokuchi S. |
タイトル | Supramolecular ferric porphyrins and a cyclodextrin dimer as antidotes for cyanide poisoning. |
ジャーナル | Hum Exp Toxicol |
Abstract |
OBJECTIVES:This study aimed to evaluate the antidotal effect of a newly developed supramolecular complex, ferric porphyrins and a cyclodextrin dimer (Fe(III)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. METHODS:First, in vitro cytochrome activity and cell viability were evaluated in murine fibroblast cells cultured with various doses of Fe(III)PIm3CD and potassium cyanide (KCN). Next, BALB/c mice were pretreated with intravenous OHCbl (0.23 mmol/kg), Fe(III)PIm3CD (0.23 mmol/kg), or saline and then received KCN (lethal dose 100% (LD100): 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. RESULTS:Fe(III)PIm3CD showed dose-dependent antidotal effects in vitro. Pretreatment with Fe(III) PIm3CD prevented KCN-induced apnea significantly better than OHCbl. Resuscitation with Fe(III)PIm3CD resulted in an earlier resumption of respiration than that seen with OHCbl. However, 24-h survival was similar among the treatments (Fe(III)PIm3CD, nine of nine mice; OHCbl, eight of nine mice). CONCLUSION:Fe(III)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. |
巻・号 | 33(4) |
ページ | 360-8 |
公開日 | 2014-4-1 |
DOI | 10.1177/0960327113499041 |
PII | 0960327113499041 |
PMID | 23918903 |
MeSH | Animals Antidotes / therapeutic use* Cyclodextrins / chemistry Cyclodextrins / therapeutic use* Dimerization Ferric Compounds / chemistry Ferric Compounds / therapeutic use* Male Mice Mice, Inbred BALB C Poisoning / drug therapy* Porphyrins / chemistry Porphyrins / therapeutic use* Potassium Cyanide / poisoning* |
IF | 2.067 |
引用数 | 5 |
WOS 分野 | TOXICOLOGY |
リソース情報 | |
ヒト・動物細胞 | NIH-3T3 |