Propachlor-S-glutathione metabolism by kidneys and ureters of calves

Six anesthetized 2- to 21-d-old male Guernsey calves weighing 28 to 61 kg were used in experiments in which either the left kidney was perfused, via the left renal artery, or the left ureter was perfused with metabolites of propachlor (2-chloro-N-acetylacetanilide, a herbicide). The glutathione conjugate of propachlor (2-S-glutathionyl-N-acetylacetanilide) was metabolized by both kidney and ureter to the cysteine conjugate (2-S-cysteinyl-N-isopropylacetanilide). The glutathione conjugate was not metabolized to the mercapturic acid conjugate (2-S-[N-acetyl]cysteinyl-N-isopropylacetanilide). When the mercapturic acid conjugate of propachlor was presented to the kidney, it was eliminated in urine. First-pass metabolism and elimination of the glutathione conjugate by the kidney was 16% of the dose, whereas first-pass elimination of the mercapturic acid was 33%. Absorption of the glutathione conjugate of propachlor, or its metabolites, or of glycine by the ureter was nil. The bovine species may be unable to form mercapturic acids from glutathione conjugates of some xenobiotics, which may make cattle more easily poisoned by these xenobiotics than chickens, pigs, and rats.