Modulation of sulphobromophthalein excretion by ethacrynic acid.
1. Ethacrynic acid (EA), a phenoxyacetic acid diuretic, has similar effects to tienilic acid (TA) on rat liver glutathione S-transferase (GST) activity in vitro, using either 1-chloro-2,4-dinitrobenzene or sulphobromophthalein (BSP) as a substrate. EA inhibits the basic rat liver GST, with inhibition being greater with GST containing subunits 3 and 4 than with those containing subunits 1 and 2. 2. In vitro inhibitors of GST can inhibit biliary excretion of BSP in a perfused liver. 3. A single bolus dose of EA had no effect on BSP excretion from the isolated perfused rat liver, and this is most likely due to the rapid disappearance of EA from the perfusion media. Experiments using perfused rat liver indicated that a sustained high concentration of EA in the perfusion media has an inhibitory effect on the excretion of both unchanged and conjugated BSP. 4. A decrease in BSP excretion may not be an indicator of liver damage, but a consequence of GST inhibition.
James
S I
SI
Key Centre for Applied and Nutritional Toxicology, RMIT University, Melbourne, Victoria, Australia.
Ahokas
J T
JT
D000818:Animals; D001646:Bile / Q000378:metabolism; D004976:Ethacrynic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013448:Sulfobromophthalein / Q000493:pharmacokinetics*
D013448:Sulfobromophthalein; D005982:Glutathione Transferase; D004976:Ethacrynic Acid