The metabolism of thiocyanate in the rat and its inhibition by propylthiouracil.

In a previous report (1) we have shown that a small fraction of the sulfur of injected thiocyanate is converted to sulfate by the rat. The conversion of thiocyanate to sulfate had been predicted to occur as the result of the physiological activity of thiocyanate ion which is known to be a goitrogen and a hypotensive agent. Our results could not be taken as unequivocal evidence for the metabolism of thiocyanate by the body because, as we have observed, thiocyanate breaks down spontaneously in aqueous solution to yield sulfate. The study did indicate that the processes which might occur in biological systems would involve rather small amounts of thiocyanate ion. An accumulation of thiocyanate in the adrenals of the rabbit has been suggested (2). Concentration of thiocyanate in the thyroid of the rat (3) has been reported also. In the latter instance the process was likened to a mass action effect. It is well known that t.hiocyanate interferes with the incorporation of iodine as thyroxine in the thyroid gland (4-6). The chemical similarity between thiocyanate and iodide suggested to us ,that the antagonism between the two ions could be metabolic. One might expect to find not only free thiocyanate ion in the thyroid fluids but also thiocyanate sulfur bound to protein and in the form of degradation products. We therefore turned to an examination of specific tissues of the animal body for evidence of the products of metabolism of thiocyanate ion. 25 mg. of radioactive potassium thiocyanate labeled with S35 were injected intraperitoneally into rats which were sacrificed at 6 and 24 hour intervals. The whole thyroids and adrenals and samples of blood plasma, muscle, and liver were pooled from groups of six animals. The tissues were homogenized and the protein was precipitated with trichloroacetic acid. The protein precipitates were freed of thiocyanate ion by “washing out” with inactive potassium thiocyanate and then oxidized by peroxide fusion. Radioactivity determinations gave a measure of thiocyanate sulfur bound to protein (Table I). Free thiocyanate ion was removed from the supernatants of the homogenates by precipitation with silver ion. The thiocyanate was oxidized to sulfate. Radioactivity determinations gave a measure of free thiocyanate in total tissue fluid (Table I).