Cyanide sulfur donors

HCN is detoxified to thiocyanate (SCN ) by the mitochondrial enzyme rhodanese rhodanese catalyzes the transfer of sulfur from thiosulfate to cyanide to yield thiocyanate, which is relatively nontoxic (Smith 1996). The rate of detoxification of HCN in humans is about 1 pg/kg/min (Schulz 1984) or 4.2 mg/h, which, the author states, is considerably slower than in small rodents. This information resulted from reports of the therapeutic use of sodium nitroprusside to control hypertension. Rhodanese is present in the liver and skeletal muscle of mammalian species as well as in the nasal epithelium. The mitochondria of the nasal and olfactory mucosa of the rat contain nearly seven times as much rhodanese as the liver (Dahl 1989). The enzyme rhodanese is present to a large excess in the human body relative to its substrates (Schulz 1984). This enzyme demonstrates zero-order kinetics, and the limiting factor in the detoxification of HCN is thiosulphate. However, other sulfur-containing substrates, such as cystine and cysteine, can also serve as sulfur donors. Other enzymes, such as 3-mercapto-pyruvate sulfur transferase, can convert... 

The metabolism of cyanide has been studied in animals. The proposed metabolic pathways shown in Figure 2-3 are (1) the major pathway, conversion to thiocyanate by either rhodanese or 3-mercapto-pyruvate sulfur transferase (2) conversion to 2-aminothiazoline-4-carboxylic acid (Wood and Cooley 1956) (3) incorporation into a 1-carbon metabolic pool (Boxer and Richards 1952) or (4) combining with hydroxocobalamin to form cyanocobalamin (vitamin B12) (Ansell and Lewis 1970). Thiocyanate has been shown to account for 60-80% of an administered cyanide dose (Blakley and Coop 1949 Wood and Cooley 1956) while 2-aminothiazoline-4-carboxylic acid accounts for about 15% of the dose (Wood and Cooley 1956). The conversion of cyanide to thiocyanate was first demonstrated in 1894. Conversion of cyanide to thiocyanate is enhanced when cyanide poisoning is treated by intravenous administration of a sulfur donor (Smith 1996 Way 1984). The sulfur donor must have a sulfane sulfur, a sulfur bonded to another sulfur (e.g., sodium thiosulfate). During conversion by rhodanese, a sulfur atom is transferred from the donor to the enzyme, forming a persulfide intermediate. The persulfide sulfur is then transferred... 

An increase in antidotal effect was noted when rhodanese was combined with thiosulfate (Frankenberg 1980). Similarly, other sulfane sulfur donors have protective effects against cyanide toxicity. 

Nitroprusside is a complex of iron, cyanide groups, and a nitroso moiety. It is rapidly metabolized by uptake into red blood cells with liberation of cyanide. Cyanide in turn is metabolized by the mitochondrial enzyme rhodanase, in the presence of a sulfur donor, to the less toxic thiocyanate. Thiocyanate is distributed in extracellular fluid and slowly eliminated by the kidney. 

The substitution chemistry of the Ru(II) and Os(II) porphyrins is synopti-cally presented in Scheme 1 and Table 4. The lability of the trans-U in MCO(P)L may be used to prepare a large variety of complexes MCO(P) L with other ligands L where the donor atom may be any oxygen-, nitrogen-, or sulfur donor (reaction path a of Scheme 1 and Table 4), cyanide (paths a, b) or carbon monoxide (c) [190]. Coordinated cyanide in [OsCO(OEP)CN]- can be transformed into isonitrile with methyifluorosulfonate [191]. 

Patients who are critical and do not satisfactorily respond to supportive therapy should be administered specific cyanide antidotes as outlined in Table 19.5. Cyanide antidotes have been classified into three main groups based on their mechanism of action (1) methemoglobin inducers, (2) sulfur donors, and (3) cobalt compounds. The definitive treatment of cyanide poisoning differs in various countries due to different medical practices and guidelines. The safety... 

Sodium thiosulfate Sulfur donors Facilitates enzymatic conversion of cyanide to thiocyanate... 

After the initial therapy of methemoglobin inducers, the cyanide has to be converted to thiocyanate which is eliminated in urine. This enzymatic detoxification of cyanide is facilitated by a sulfur donor like sodium thiosulfate. The mechanism of this reaction was discussed earlier under elimination of cyanide. High tissue oxygen markedly potentiates the effects of this reaction. In cases where methemoglobin formation is not desirable, sodium thiosulfate together with oxygen alone is sufficient. The utility of... 

Sulfur donors for conversion of cyanide to thiocyanate by rhodanese or other sulfur transferases, that is, a source of sulfur. For moderate poisoning, sodium thiosulfate is the usual choice. 

Cyanide is metabolized by the ubiquitous enzyme rhodanase to thiocyanate (SCN"), drawing on the body s sulfur-donor pool for substrate to convert CN" to SCN". Thiocyanate is relatively inert and is cleared by the kidney. The conversion of CN" to SCN" occurs slowly relative to the pharmacological action of CN", so measurement of SCN" is of use in monitoring clearance but not very useful in assessing acute CN" exposure. In an acute exposure, the patient experiences symptoms of toxicity with high blood CN" levels, but the serum SCN" level remains low until 12 to 24 hours later. 

C. M., and Ternay, A.L. In vitro and in vivo comparison of sulfur donors as antidotes to acute cyanide intoxication, J. Appl. Toxicol, 19,173,1999. 

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