RRC ID 44789
Author Yamagiwa T, Inokuchi S, Saito T, Inoue S, Morita S, Kawaguchi AT.
Title A stable in vitro method for assessing the toxicity of potassium cyanide and its antidote.
Journal Tokai J Exp Clin Med
Abstract BACKGROUND:Hydrogen cyanide possesses a high acid-dissociation constant of 9.14, favoring its vaporization and depletion from the culture media at physiological pH, which may cause the cyanide toxicity unstable in vitro.
OBJECTIVE:We investigated whether adjustment of culture medium pH stabilizes cyanide concentration and decreases the effective concentration of potassium cyanide (KCN).
METHODS:Murine fibroblast cells were exposed to different concentrations of KCN in media maintained at pH 7.4 or 9.2, in the presence or absence of hydroxocobalamin. After incubation for 1 h, we evaluated medium pH, cyanide concentration, cytochrome activity, and cell viability.
RESULTS:Cyanide concentration decreased to 18.8% in pH 7.4 medium compared to 83.2% in pH 9.2 medium. A significant decrease in cytochrome activity was observed at 40 mM and 1.25 mM KCN in pH 7.4 and pH 9.2 media, respectively. In pH 9.2 medium, dose-dependent cytotoxicity of KCN and antidotal effects of hydroxocobalamin were observed.
CONCLUSION:Adjustment of culture medium pH to 9.2 could stabilize cyanide concentration and decrease the effective concentration of KCN, allowing stable evaluation of KCN toxicity and antidotal efficacy.
Volume 38(4)
Pages 114-22
Published 2013-12-20
PMID 24318282
MeSH Animals Antidotes / pharmacology* Cell Survival / drug effects* Cells, Cultured Culture Media / chemistry* Cytochromes / metabolism Dose-Response Relationship, Drug Fibroblasts / drug effects* Fibroblasts / enzymology Hydrogen-Ion Concentration Hydroxocobalamin / pharmacology* Mice Potassium Cyanide / analysis* Potassium Cyanide / toxicity* Toxicity Tests / methods* Volatilization
Resource
Human and Animal Cells NIH3T3