Effect of peroxisome proliferators on glutathione-dependent sulphobromophthalein excretion.
1. The effect of pretreatment of rats with the peroxisome proliferator 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) on sulphobromophthalein excretion from the isolated perfused rat liver has been investigated and compared with the effect of clofibrate which is also a peroxisome proliferator. 2. Rats fed 2,4,5-T at a dose of 0.25% in the diet showed a decrease in food intake, compared with controls and clofibrate-fed rats. 3. Treatment with either 2,4,5-T or clofibrate was associated with significant inhibition of the biliary excretion of unchanged, conjugated, and total sulphobromophthalein from perfused rat liver, compared with diet-matched controls. 4. There was a decrease in bile flow in the clofibrate-treated group, but not in the 2,4,5-T-treated group. 5. The results of the present study confirm previous studies that have shown an association between peroxisome proliferation treatment and inhibition of glutathione S-transferase-mediated sulphobromophthalein excretion.
James
S I
SI
Key Centre for Applied and Nutritional Toxicology, RMIT University, Melbourne, Victoria, Australia.
Ahokas
J T
JT
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology; D005978:Glutathione / Q000502:physiology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013448:Sulfobromophthalein / Q000493:pharmacokinetics*
D013448:Sulfobromophthalein; D015085:2,4,5-Trichlorophenoxyacetic Acid; D005978:Glutathione; D002994:Clofibrate