Antidotal effect of dihydroxyacetone against cyanide toxicity in vivo.
Potassium cyanide (CN) intoxication in mice was found to be effectively antagonized by dihydroxyacetone (DHA), particularly if administered in combination with another CN antidote, sodium thiosulfate. Cyanide-induced convulsions were also prevented by DHA treatment, either alone or in combination with thiosulfate. Injection (i.p.) of DHA (2 g/kg) 2 min after or 10 min before CN (s.c.) increased LD50 values of CN(8.7 mg/kg) by factors of 2.1 and 3.0, respectively. Treatment with a combination of DHA and thiosulfate after CN increased the LD50 by a factor of 2.4. Pretreatment with a combination of DHA and thiosulfate (1 g/kg) increased the LD50 of CN to 83 mg/kg. Administration of alpha-ketoglutarate (2.0 g/kg), but not pyruvate, 2 min after CN increased the LD50 of CN by a factor of 1.6. Brain, heart and liver cytochrome oxidase activities were also measured following in vivo CN treatment with and without DHA. Pretreatment with DHA prevented the inhibition of cytochrome oxidase activity by CN and treatment with DHA after CN accelerated the recovery of cytochrome oxidase activity, especially in brain and heart homogenates. DHA is a physiological agent and, therefore, could prove to be a safe and effective antidote for CN, particularly in cases of fire smoke inhalation in which a combination of CN and carbon monoxide is present. In these cases the normally used antidote, sodium nitrite, to induce methemoglobin so as to trap the CN, is contraindicated because some of the oxygen-carrying capacity of the blood will have already been diminished by carbon monoxide.
Niknahad
H
H
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
O'Brien
P J
PJ
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D004098:Dihydroxyacetone / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D007656:Ketoglutaric Acids / Q000494:pharmacology; D007928:Lethal Dose 50; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000201:enzymology; D011190:Potassium Cyanide / Q000037:antagonists & inhibitors / Q000506:poisoning*; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D012977:Sodium Nitrite / Q000494:pharmacology; D013885:Thiosulfates / Q000494:pharmacology
D000931:Antidotes; D007656:Ketoglutaric Acids; D011773:Pyruvates; D013885:Thiosulfates; D019289:Pyruvic Acid; D003576:Electron Transport Complex IV; C017717:sodium thiosulfate; D012977:Sodium Nitrite; D011190:Potassium Cyanide; D004098:Dihydroxyacetone