The oxidative disposition of potassium cyanide in mice.
The role of oxidative metabolism in the disposition of potassium cyanide (KCN), was investigated in mice administered KCN, (4.6 mg/kg, s.c.) containing 4.5 microCi [14C]KCN. The expired pulmonary metabolites, [14C]hydrocyanic acid (HCN) and 14CO2, were collected and analyzed. Approximately 1% and 2% of the KCN dose was expired as [14C]HCN and 14CO2, respectively. Expiration of the pulmonary metabolites was decreased following pretreatment with sodium nitrite, sodium thiosulfate, oxygen, or a combination of cyanide antidotes. Treatment with hydrogen peroxide lowered the amount of [14C]HCN expired and did not alter the expiration of 14CO2. Treatment with 3-amino-1,2,4-triazole (catalase inhibitor), superoxide dismutase, or diethyldithiocarbamic acid (superoxide dismutase inhibitor) did not change the amount of [14C]HCN expired. However, superoxide dismutase significantly increased the amount of 14CO2 expired, whereas diethyldithiocarbamic acid decreased 14CO2 expiration. The results from these studies suggest that in vivo cyanide can be oxidized to CO2 and treatment with agents that alter the availability of endogenous superoxide and/or hydrogen peroxide can alter the rate of cyanide oxidation.
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001944:Breath Tests; D002245:Carbon Dioxide / Q000032:analysis; D002250:Carbon Radioisotopes; D003486:Cyanides / Q000378:metabolism*; D004347:Drug Interactions; D006856:Hydrogen Cyanide / Q000032:analysis; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008658:Inactivation, Metabolic; D007279:Injections, Subcutaneous; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D011190:Potassium Cyanide / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology
D002250:Carbon Radioisotopes; D003486:Cyanides; D002245:Carbon Dioxide; D006856:Hydrogen Cyanide; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D011190:Potassium Cyanide; D010100:Oxygen; D000640:Amitrole