THE METABOLIC REDUCTION AND NEPHROTOXIC ACTION OF TETRATHIONATE IN RELATION TO A POSSIBLE INTERACTION WITH SULFHYDRYL COMPOUNDS

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Abstract
In the rabbit and the dog, tetrathionate is rapidly reduced to thiosulfate. Coincidently there is observed a nephrotoxic action of such severity that in anesthetized, catheterized dogs complete anuria results within 30-60 mins. after the injn. of moderate doses. Pathological examination reveals a discrete lesion of the cells of the proximal tubule which has advanced to the stage of nuclear degeneration within 30 min. It is possible to reduce tetrathionate in vitro with 2,3-dimercaptopropanol, 1-thiosorbitol, cysteine, and glutathione with the stoichiometric formation of the corresponding disulfides. That thiols can react with tetrathionate in vivo is evident from the fact that the prophylactic admn. of 1-thiosorbitol or cysteine protects against the nephrotoxic action of tetrathionate. Evidence is presented that the distribution and site of reduction of tetrathionate are extracellular. Two alternative theories are presented that 1, tetrathionate selectively permeates the cells of the proximal tubule to exert a direct toxic action on catalytic systems dependent on the presence of [long dash]SH, or 2, the cells of the proximal tubules are selectively damaged by the removal of diffusible [long dash]SH compounds.

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