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Complexation of intracellular cyanide by hydroxocobalamin using a human cellular model
Human & Experimental Toxicology
|January 1, 1996
Summary
Hydroxocobalamin (OHCbl) effectively reduces intracellular cyanide levels by forming non-toxic cyanocobalamin (CNCbl). This antidote penetrates cyanide-loaded cells, demonstrating its potential in cyanide poisoning treatment.
Area of Science:
- Toxicology
- Biochemistry
- Pharmacology
Background:
- Cyanide poisoning treatment relies on antidotes like hydroxocobalamin (OHCbl) due to cyanide's affinity for cobalt.
- Limited data exists on OHCbl's effect on intracellular cyanide pools.
Purpose of the Study:
- To investigate the influence of OHCbl on intracellular cyanide accumulation and detoxification.
- To assess OHCbl's efficacy in reducing intracellular cyanide levels in human cells.
Main Methods:
- Incubation of human fibroblasts and U-937 cells with radiolabeled cyanide.
- Measurement of intracellular cyanide accumulation ratios at different temperatures.
- Analysis of cyanide uptake kinetics and the effect of OHCbl treatment.
Main Results:
- Significant intracellular cyanide accumulation observed in fibroblasts (ratio 25 at 37°C).
- Rapid cyanide uptake by U-937 cells showed a linear relationship with concentration.
- OHCbl treatment decreased intracellular cyanide by 75% and formed cyanocobalamin (CNCbl).
Conclusions:
- Hydroxocobalamin effectively penetrates cyanide-loaded cells.
- OHCbl complexes intracellular cyanide into the non-toxic form, cyanocobalamin.
- These findings support OHCbl's role as a potent cyanide poisoning antidote.
