Supramolecular ferric porphyrins and a cyclodextrin dimer as antidotes for cyanide poisoning
Objectives: This study aimed to evaluate the antidotal effect of a newly developed supramolecular complex, ferric porphyrins and a cyclodextrin dimer (FeIIIPIm3CD), that possess a higher binding constant and quicker binding rate to cyanide ions than those of hydroxocobalamin (OHCbl) in the presence...
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Veröffentlicht in: | Human & experimental toxicology 2014-04, Vol.33 (4), p.360-368 |
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Sprache: | eng |
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Zusammenfassung: | Objectives:
This study aimed to evaluate the antidotal effect of a newly developed supramolecular complex, ferric porphyrins and a cyclodextrin dimer (FeIIIPIm3CD), 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 FeIIIPIm3CD and potassium cyanide (KCN). Next, BALB/c mice were pretreated with intravenous OHCbl (0.23 mmol/kg), FeIIIPIm3CD (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:
FeIIIPIm3CD showed dose-dependent antidotal effects in vitro. Pretreatment with FeIII PIm3CD prevented KCN-induced apnea significantly better than OHCbl. Resuscitation with FeIIIPIm3CD resulted in an earlier resumption of respiration than that seen with OHCbl. However, 24-h survival was similar among the treatments (FeIIIPIm3CD, nine of nine mice; OHCbl, eight of nine mice).
Conclusion:
FeIIIPIm3CD 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. |
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ISSN: | 0960-3271 1477-0903 |
DOI: | 10.1177/0960327113499041 |