The antidote effect of thiosulphate and hydroxocobalamin in formation of nitroprusside intoxication of rabbits.
Sodium nitroprusside (SNP) and hydroxocobalamin (HC) - in molar ratios of 1:4, 1:5, and 1:8, respectively - were infused simultaneously during 4 h into two veins of separate ears of conscious rabbits. Controls received HC only. Sodium thiosulphate (ST) was infused with SNP at molar ratios of 1:4, 1:5, and 1:10. The observation period was 48 h. With the lowest dose of HC (1:4), SNP produced a severe metabolic acidosis; three of ten animals died during the infusion, an additional six within 24 h. When the 1:5 ratio was administered, the acidosis was less marked, but still three of seven animals succumbed within 24 h. The highest dose (1:8) prevented acidosis, however three of eight animals died. All doses of HC caused histological changes in the liver, the myocardium, and the kidney, independently if given alone or with SNP. In contrast to this, ST had a complete antidote effect, if administered in a 1:5 ratio; no acidosis was demonstrable and death did not occur. In neither dosage ST could prevent histological changes in the liver, but the kidney and the heart were not affected. In contrast to HC ST alone did not cause histological alterations. Consequently, ST is the preferable antidote and is superior to HC for preventing or treating intoxications with SNP.
D000818:Animals; D004359:Drug Therapy, Combination; D005292:Ferricyanides / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D006879:Hydroxocobalamin / Q000008:administration & dosage* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D009599:Nitroprusside / Q000633:toxicity*; D011817:Rabbits; D013885:Thiosulfates / Q000008:administration & dosage* / Q000633:toxicity
D005292:Ferricyanides; D013885:Thiosulfates; D009599:Nitroprusside; D006879:Hydroxocobalamin