Nitroprusside intoxication: protection of alpha-ketoglutarate and thiosulphate.
Protection against the lethal effects of sodium nitroprusside (SNP) was observed in mice after treatment with alpha-ketoglutarate (AKG), either alone or in combination with sodium thiosulphate (STS). The LD50 of SNP was 12.0 (11.0-13.0) mg/kg in mice. Ip injection of AFG (500 mg/kg twice in 20 min) increased the LD50 1.7-fold in mice. STS (1 g/kg, ip) alone increased the LD50 5.5-fold. Furthermore, combined administration of AKG and STS increased the LD50 6.9-fold. SNP elicited increased cyanide levels in blood of mice in a dose-dependent manner. SNP (10 mg/kg, sc) administration gave rise to blood cyanide levels of 73.2 +/- 3.0 microM, 30 min after treatment. Ip injection of AKG significantly decreased blood cyanide levels by 30% in mice 30 min after treatment with 10 mg SNP/kg. A single injection of STS (1 g/kg) or a combination of AKG and STS reduced in blood cyanide levels by 88 or 98%, respectively, in mice after treatment with 10 mg SNP/kg. In addition, the increase in blood cyanide levels induced by injection of 50 mg SNP/kg was markedly inhibited by a combination of AKG and STS or (to a lesser extent) by STS alone. These results suggest that the combined administration of AKG and STS, by preventing the increase in blood cyanide levels induced by SNP, may afford protection against the toxic effects of SNP.
Yamamoto
H A
HA
Department of Environmental Medicine, University of Tsukuba, Ibaraki, Japan.
D000818:Animals; D003486:Cyanides / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007656:Ketoglutaric Acids / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009599:Nitroprusside / Q000008:administration & dosage / Q000633:toxicity*; D013885:Thiosulfates / Q000008:administration & dosage / Q000494:pharmacology*
D003486:Cyanides; D007656:Ketoglutaric Acids; D013885:Thiosulfates; D009599:Nitroprusside; C017717:sodium thiosulfate