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Abstract
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 LD1S 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). Combinations of alpha-ketoglutaric acid and sodium thiosulfate proved to be very effective. Injections in which alpha-ketoglutaric acid and sodium thiosulfate (200 and 500 mg/kg, respectively) were given 15 min prior to NaCN challenges of 26.5 mg/kg (4.8 x LD50) produced an average lethality of 78%. Greater doses of alpha-ketoglutaric acid and sodium thiosulfate were required to provide protection against the lethal effects of inhaled HCN than those of parenteral NaCN. Also, alpha-ketoglutaric acid and sodium thiosulfate are synergistic in their antidotal effects against both HCN and NaCN.