title: Supramolecular ferric porphyrins and a cyclodextrin dimer as antidotes for cyanide poisoning.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Isehara Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamagiwa
authors.forename: A T
authors.initials: AT
authors.lastname: Kawaguchi
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Kitagishi
authors.forename: K
authors.initials: K
authors.lastname: Koji
authors.forename: S
authors.initials: S
authors.lastname: Inokuchi
mesh_terms: D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D003505:Cyclodextrins / Q000737:chemistry / Q000627:therapeutic use*; D019281:Dimerization; D005290:Ferric Compounds / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011041:Poisoning / Q000188:drug therapy*; D011166:Porphyrins / Q000737:chemistry / Q000627:therapeutic use*; D011190:Potassium Cyanide / Q000506:poisoning*
chemical_list: D000931:Antidotes; D003505:Cyclodextrins; D005290:Ferric Compounds; D011166:Porphyrins; D011190:Potassium Cyanide
keywords: Cyanide; antidote; hydroxocobalamin; imidazole linker