Effect of AT-125 on the metabolism of propachlor and the glutathione conjugates of propachlor and bromobenzene in rat.
1. Dosing rats with the gamma-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.
Bakke
J E
JE
US Department of Agriculture, Agriculture Research Service, Biosciences Research Laboratory, Fargo, ND 58105-5674.
Larsen
G L
GL
Davison
K L
KL
D000083:Acetanilides / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001652:Bile Ducts; D001969:Bromobenzenes / Q000378:metabolism*; D002404:Catheterization; D005978:Glutathione / Q000378:metabolism* / Q000652:urine; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors*
D000083:Acetanilides; D001969:Bromobenzenes; D007555:Isoxazoles; C011088:propachlor; C032036:bromobenzene; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C006303:acivicin