Further investigations on the metabolism of 2:3-dimercaptopropanol.

Although 2:3-dimercaptopropanol (British AntiLewisite, BAL) was first introduced (Stocken & Thompson, 1941, 1946) as a local antidote for use after contamination of the skin with one of the arsenical vesicants, its application to the treatment of systemic arsenical poisoning in man made it desirable to obtain information concerning the distribution of thiols in the blood and urine after injection of BAL. In this laboratory (Thompson & Stocken, 1941) it had been shown that shortly after the injection of BAL into rabbits and rats the urine of the animals developed a strong nitroprusside reaction for thiol groups, accompanied by a large increase in the iodine titre of the urine. The nitroprusside reaction, which is ordinarily negative, again disappeared and the iodine titre fell to its previous value within a few hours of the injection. In order to obtain more precise information regarding the nature of the urinary thiols, the cobalt method for the estimation of BAL (Calvery, 1943; Spray, 1947) has been applied to the urine ofrabbits after injection of BAL. Owing to the limited specificity of this reaction (Spray, 1947), a series of experiments was carried out in which the reactions of BAL with salts of other metals were examined, and compared with those given by the thiol appearing in the urine after injection ofBAL. These experiments, however, did not by themselves provide conclusive evidence as to the nature ofthe thiols present in rabbit urine after injection of BAL, and further evidence was therefore sought. The extraction and purification of the thiols from rabbit urine were investigated, and a procedure was evolved, based on the precipitation of the thiols with the thallous ion in alkaline solution, and subsequent decomposition of the metal complex with H2S. In this way relatively pure and concentrated preparations of urinary thiols could be obtained. The reactions with metal salts were then reexamined using the purified thiol, and in addition, through the kindness of Mr E. R. Holiday, a comparison of the absorption spectra of the colours formed by reaction of the cobalt reagent with BAL and with the excreted thiol was made, in order to obtain more precise information regarding the identity of the coloured derivatives. The thiol was then tested for its ability to protect the pyruvate oxidase enzyme system of brain from inhibition by lewisite. By this means it was hoped to obtain biochemical evidence which would help to characterize the excreted thiol as either a monoor a dithiol, since it has been shown (Stocken & Thompson, 1941, 1946) that this enzyme system can be completely protected from the toxic action of lewisite oxide by dithiols at concentrations at which all the monothiols that have been studied are completely ineffective (Sinclair, 1940).