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Drug Metab Dispos ; 16(2): 189-95, 1988.
Article in English | MEDLINE | ID: mdl-2898331

ABSTRACT

The in vivo renal tubular secretion and metabolism of the disulfide of the heavy metal-complexing agent 2,3-dimercaptopropane-1-sulfonate (DMPS) was examined in the Sperber preparation. DMPS was readily oxidized to DMPS disulfide when incubated with chicken plasma, with whole blood or with urine in the presence of transition metals. Net reduction of the disulfide was not detected when the disulfide was incubated with chicken blood. When the disulfide was infused into the saphenous vein of chickens at a rate of 1 mumol of DMPS equivalents.min-1.kg of body weight-1, 62% of the DMPS disulfide that entered the renal portal circulation of the ipsilateral kidney was excreted in the urine unchanged during a single pass through the peritubular capillaries, 28% was excreted as DMPS, and 9% as an unidentified mixed disulfide. Net reduction of DMPS disulfide to DMPS occurred in vitro in rat kidney cytosol (pH 7.4) supplemented with 0.5 or 5.0 mM reduced glutathione. Reduction of DMPS disulfide to DMPS also occurred in EDTA-Tris HCl (pH 9) containing glutathione disulfide and glutathione reductase. Intracellular reduction of DMPS disulfide to DMPS in the kidney, involving a glutathione-disulfide exchange reaction, may be important for the in vivo activity of DMPS as a complexing agent for mercury.


Subject(s)
Dimercaprol/analogs & derivatives , Kidney Tubules/metabolism , Unithiol/analogs & derivatives , Animals , Chickens , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Cytosol/metabolism , Disulfides/metabolism , Female , Oxidation-Reduction , Unithiol/blood , Unithiol/metabolism , Unithiol/urine
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