Metabolism of the glutathione conjugate of propachlor by in situ perfused kidneys and livers of rats

Abstract

1. [1-¹⁴C]Propachlor-GSH was perfused at 0.34, 3.4 and 34 μmol/h through the portal vein or the right renal artery of anaesthetized rats with biliary and ureteral cannulas. Urine was the predominant route for elimination of the ¹⁴C regardless of the route of perfusion.

2. Mercapturic acid conjugates were found to be the end-products of metabolism of the ¹⁴C-propachlor-GSH by rat kidneys and liver, indicating that all enzymes necessary for the catabolism of GSH conjugates to mercapturates were present in each of these tissues.

3. Perfusion of ¹⁴C-propachlor-GSH at 34 μmol/h appeared to exceed the metabolic capacity of both liver and kidneys for this substrate. At this dose, parent compound was detected in the bile of portally perfused rats, and the amounts of ¹⁴C recovered in bile, kidneys and carcasses of renally perfused rats were greater than when smaller dosages were perfused.