Shafer P R, Wilcox D E, Kruszyna H, Kruszyna R, Smith R P
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03756.
Toxicol Appl Pharmacol. 1989 Jun 1;99(1):1-10. doi: 10.1016/0041-008x(89)90105-1.
Most investigators agree that sodium nitroprusside (SNP) undergoes biotransformation in vivo to release free cyanide (CN-). Despite a demonstrated reactivity of SNP toward oxyhemoglobin (HbO2) in vitro, that reaction is probably not the major cause for CN- release in vivo. An unknown reaction in various vascular beds inactivates SNP more rapidly than the reaction in blood, but both result in the release of free CN-. Recently it has been claimed that SNP is stable in blood and that the apparent CN- release is an artifact due to photodecomposition of SNP during CN- analyses. In this study the release of free CN- from SNP was followed over 3 hr of incubation in plain buffer, in suspensions of red blood cells (RBC), in lysates, and in solutions of HbO2 purified by isoelectric focusing and shown to be free of methemoglobin (MetHb), valency hybrid species, and reduced glutathione (GSH). In each case the mixtures containing HbO2 released significantly more CN- than plain buffer where CN- release was at the limit of sensitivity of the method. Moreover, in the order of RBC, purified HbO2 solutions and lysates, each preparation released significantly more CN- in 1 hr than the preceding one. In lysates the reaction had gone to completion by 3 hr. Using 13C nuclear magnetic resonance (NMR) spectroscopy, SNP was shown to be inert to CN- exchange in solutions of Na13CN, but when GSH or MetHb was added, an exchange reaction occurred between the trans-CN- of SNP and 13CN- in solution. The same reaction proceeded even more rapidly in the presence of HbO2. The results of this study show that in the presence of GSH, MetHb and particularly in the presence of HbO2, SNP readily exchanges its trans-CN- ligand with excess free CN-. This reaction is believed to represent an obligatory precursor step in the total decomposition of SNP which occurs in the absence of free CN-, but in the presence of RBC, solutions of HbO2, and lysates. It appears that excess free CN- halts total decomposition at the stage of trans-CN- labilization.
