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Complexation of intracellular cyanide by hydroxocobalamin using a human cellular modelLaboratoire de Toxicologie, Service de Pharmacie, CHU Henri Mondor 94010 Créteil, France
Réanimation Toxicologique, Hopital Fernand Widal, Paris, France 1 The rational for administering hydroxocobalamin (OHCbl) as an antidote to cyanide poisoning is based on the high affinity ofCN 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 µM of [14C] cyanide, the accumulation ratio was 25 at 37°C (10.45 ± 1.51 mM) and 11.9 at 4°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 µM; 5 min) was found suggesting a first order process (k= 0.25 min-1). 5 After incubation of fibroblasts with 500 µM 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.
Key Words: cyanide antidote hydroxocobalamin cyanocobala min cellular model
Human & Experimental Toxicology, Vol. 15, No. 1,
19-25 (1996) |
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