Abstract
The classical cyanide antagonists, nitrite and thiosulfate, protect laboratory rodents against death by sodium nitroprusside, Na2Fe(CN)5NO. On a molar basis, sodium nitroprusside is at least 4 times more acutely toxic than sodium cyanide to mice. Lethal blood levels of cyanide are found in mice at death after nitroprusside. Cyanide can be released from nitroprusside when the latter is incubated with a variety of biological materials. This reaction is nonenzymatic and apparently involves free sulfhydryl groups. The most active biological preparation tested was blood. The red cells were far more active than plasma, and mouse and rat erythrocytes were more active than human red cells. Hemolysis resulted in even greater activity and abolished the species differences. In solution nitroprusside reacts with oxy- or deoxyhemoglobin to generate cyanmethemoglobin. Such a direct conversion of hemoglobin to cyanmethemoglobin by reaction with a single molecular species has not previously been described. In the presence of dithionite, the product is nitric oxide hemoglobin. Under appropriate conditions, intracellular formation of cyanmethemoglobin can be demonstrated in erythrocytes exposed to nitroprusside. Higher concentrations of cyanmethemoglobin are generated in rat erythrocytes than in human erythrocytes suggesting that the above species differences are related to differences in the permeability of various red cells to nitroprusside. The principal source of the free cyanide generated in animals after nitroprusside appears to result from the reaction of the latter with hemoglobin. A similar reaction could almost certainly be elicited in man.
Footnotes
- Received May 6, 1974.
- Accepted August 1, 1974.
- © 1974 by The Williams & Wilkins Co.
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