Supramolecular ferric porphyrins and a cyclodextrin dimer as antidotes for cyanide poisoning

Abstract

Objectives:

This study aimed to evaluate the antidotal effect of a newly developed supramolecular complex, ferric porphyrins and a cyclodextrin dimer (Fe^IIIPIm3CD), 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^IIIPIm3CD and potassium cyanide (KCN). Next, BALB/c mice were pretreated with intravenous OHCbl (0.23 mmol/kg), Fe^IIIPIm3CD (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^IIIPIm3CD showed dose-dependent antidotal effects in vitro. Pretreatment with Fe^III PIm3CD prevented KCN-induced apnea significantly better than OHCbl. Resuscitation with Fe^IIIPIm3CD resulted in an earlier resumption of respiration than that seen with OHCbl. However, 24-h survival was similar among the treatments (Fe^IIIPIm3CD, nine of nine mice; OHCbl, eight of nine mice).

Conclusion:

Fe^IIIPIm3CD 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.