Effect of AT-125 on the metabolism of propachlor and the glutathione conjugates of propachlor and bromobenzene in rat

Abstract

1. Dosing rats with the γ-glutamyl-transpeptidase inhibitor AT-125 results in the excretion of free glutathione in the urine of rat: this treatment did not lead to the excretion of glutathione conjugates of orally dosed xenobiotics, neither did AT-125 increase the biliary excretion of glutathione conjugates.

2. Dosing rat with AT-125 prior to dosing with 2-chloro-N-isopropylacetanilide decreased the excretion of 2-methylsulphonylacetanilide metabolites from 23% of the dose to >0.5%.

3. We conclude that glutathione and glutathione-xenobiotic conjugates are probably not processed in vivo by the same pathway, and that AT-125 can alter the in vivo transport of mercapturic acid pathway metabolites.