Reference - Detail
| RRC ID | 44572 |
|---|---|
| Author | Yamagiwa T, Kawaguchi AT, Saito T, Inoue S, Morita S, Watanabe K, Kitagishi H, Koji K, Inokuchi S. |
| Title | Supramolecular ferric porphyrins and a cyclodextrin dimer as antidotes for cyanide poisoning. |
| Journal | 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. |
| Volume | 33(4) |
| Pages | 360-8 |
| Published | 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 |
| Times Cited | 5 |
| WOS Category | TOXICOLOGY |
| Resource | |
| Human and Animal Cells | NIH-3T3 |