Antidotal efficacy of alpha-ketoglutaric acid and sodium thiosulfate in cyanide poisoning.
Alpha-ketoglutaric acid and sodium thiosulfate antagonize the toxic effects of cyanide. The present study was performed to test whether a synergistic effect may occur. The alpha-ketoglutaric acid/sodium thiosulfate solutions were injected intraperitoneally into mice prior to exposure to hydrogen cyanide (HCN) in a dynamic inhalation chamber or preceding an intraperitoneal injection of sodium cyanide (NaCN). All lethal concentration (LCT) and lethal dose (LD) values were determined after a period of 24 h. Alpha-ketoglutaric acid alone provided no protection at 250 mg/kg when challenged with HCN. Sodium thiosulfate 500 mg/kg provided a 5% protection. However, when these doses of alpha-ketoglutaric acid and sodium thiosulfate were combined, protection was increased by 18%. Alpha-ketoglutaric acid (250 mg/kg) and sodium thiosulfate (1000 mg/kg) provided an additional 48% protection against a LCT88 of HCN. A single dose of alpha-ketoglutaric acid (500 mg/kg) and sodium thiosulfate (1000 mg/kg) solutions afforded a 70% increase in survivability of the exposed animals. When mice were injected ip with 100 mg/kg of alpha-ketoglutaric acid 15 min prior to the injection of 5.5 mg/kg (LD50) of NaCN, the lethality was reduced to an LD30. Two hundred mg/kg alpha-ketoglutaric acid, challenged with the same dose of NaCN, reduced the lethality to 23%. When mice were challenged with 6.0 mg/kg of NaCN (LD70) pretreated with 100 mg/kg of alpha-ketoglutaric acid or 200 mg/kg of sodium thiosulfate, the LD was not altered in the former but reduced to an LD15 in the latter. At higher doses of sodium thiosulfate (500 mg/kg), an LD60 occurred at 13.6 mg/kg NaCN (2.5 x LD50).(ABSTRACT TRUNCATED AT 250 WORDS)
University of Mississippi Medical Center, Jackson 39216, USA.
A S
AS
Hume
J R
JR
Mozingo
B
B
McIntyre
I K
IK
Ho
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006856:Hydrogen Cyanide / Q000506:poisoning*; D007656:Ketoglutaric Acids / Q000627:therapeutic use*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012966:Sodium Cyanide / Q000506:poisoning; D015996:Survival Rate; D013885:Thiosulfates / Q000627:therapeutic use*
D000931:Antidotes; D007656:Ketoglutaric Acids; D013885:Thiosulfates; D006856:Hydrogen Cyanide; C017717:sodium thiosulfate; D012966:Sodium Cyanide