Complexation of intracellular cyanide by hydroxocobalamin using a human cellular model.
1. The rational for administering hydroxocobalamin (OHCbl) as an antidote to cyanide poisoning is based on the high affinity of CN ion for cobalt compounds. However, only few data are available on the influence of OHCbl on the intracellular cyanide pool. 2. In human fibroblasts incubated for 10 min with 500 microM of [14C] cyanide, the accumulation ratio was 25 at 37 degrees C (10.45 +/- 1.51 mM) and 11.9 at 4 degrees C. 3. Using the monoblastic U-937 cell line, a rapid uptake of radioactive cyanide was observed with a maximum accumulation ratio of 1.97 at 5 min. 4. A linear relationship between cyanide uptake by U-937 cells and cyanide concentration in incubation medium (10-500 microM; 5 min) was found suggesting a first order process (k = 0.25 min-1). 5. After incubation of fibroblasts with 500 microM of OHCbl, a 75% decrease of intracellular cyanide was observed, with concomittant formation of intracellular cyanocobalamin CNCbl (intracellular/extracellular ratio: 158). 6. These findings suggest that OHCbl is able to penetrate into heavily cyanide loaded cells and to complex cyanide to the non-toxic CNCbl form.
Astier
A
A
Service de Pharmacie, CHU Henri Mondor, Créteil, France.
Baud
F J
FJ
D000931:Antidotes / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003486:Cyanides / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D005347:Fibroblasts / Q000378:metabolism; D006397:Hematinics / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006879:Hydroxocobalamin / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D014805:Vitamin B 12 / Q000378:metabolism
D000931:Antidotes; D003486:Cyanides; D006397:Hematinics; D014805:Vitamin B 12; D006879:Hydroxocobalamin