RAPID, SUBSTRATE-SPECIFIC, AND DOSE-DEPENDENT DEACTIVATION OF LIVER CYTOSOLIC GLUTATHIONE S-TRANSFERASES INVIVO BY 1,1-DICHLOROETHYLENE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 47  (1) , 59-72
Abstract
Administration of 200 mg 1,1-dichloroethylene (1,1-DCE) per kg to fasted male rats rapidly decreased liver cytosolic glutathione (GSH) S-transferase activities by half within 1 h. This early decrease was not associated with increased serum activities of this soluble enzyme and is considered due to enzyme deactivation. The early decrease in enzyme activities was concomitant with a 3/4 depletion of cytosolic GSH and preceded changes in cytochrome P-450 and the onset of liver cytotoxicity, both of which occurred abruptly between 2 and 3 h. Substantial changes in GSH S-transferase activities at 4 h were produced only by severely hepatotoxic doses of 1,1-DCE. The early decrease in hepatic GSH S-transferase activities was selective for substrates dichloronitrobenzene, chlorodinitrobenzene and 1,2-epoxy-3-(p-nitrophenoxy)propane with apparent sparing of activity towards ethacrynic acid. The rapid, selective and dose-dependent deactivation of the hepatic GSH S-transferases could be relevant to the catastrophic hepatotoxicity of 1,1-DCE.