RRC ID 44572
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