Chronic cyanide intoxication is a public health problem with drastic deleterious effects on a very large number of people in the agrarian tropics, where consumption of foods rich in cyanogenic glycosides in widespread. Similar but less drastic effects occur in modern industrial society, where frequent exposure to smaller amounts of cyanide from many sources is increasingly unavoidable. Systematic development of rational strategies for combatting these effects will depend on a correct detailed understanding of the natural mechanisms of cyanide detoxication. Such an understanding is presently lacking. The long term objectives of the proposed research are to relieve this deficiency and thereby to initiate a rational prophylactic approach to the practical problem. Since there is little doubt that cyanide is detoxified in mammals principally by conversion to thiocyanate in a reaction with some from of sulfane sulfur, the first specific aim of this research is to establish the quantitative sulfane sulfur distribution profiles of blood and various tissues. Because serum albumin has been shown to be capable of transporting sulfane sulfur, and additional aim is the characterization of the albumin binding sites for sulfur in relation to the sites previously established for a variety of other metabolites and drugs. Since serum albumin can also catalyze the detoxifying reaction of its sulfane sulfur with cyanide, a further aim is to establish the sources and circumstances of sulfur loading and unloading in normal metabolism. Finally, the beginnings of a prophylactic strategy will be sought in efforts to augment selectively the sulfane sulfur profiles of blood and tissues, and the relevance of such manipulation will be sought in radioisotopic tracer kinetic studies in vivo. The results of these studies are expected to be importance in the recognition, treatment, and prevention of disease conditions, often of complex etiology, involving chronic intoxication with cyanide.
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