The hepatocellular transport of sulfobromophthalein-glutathione by clofibrate treated, perfused rat liver.
The hypolipidemic drug clofibrate is known to affect the hepatic transport of various organic anions including bilirubin, fatty acids and sulfobromophthalein. Changes in the rate of metabolism and/or intracellular transport have been claimed responsible for the effect. To evaluate these possibilities, the transport of sulfobromophthalein-glutathione, a model compound that does not require metabolism for biliary excretion, was studied in perfused livers isolated from clofibrate-treated and control rats. Cytosolic fatty acid binding protein and glutathione S-transferase activity were also measured. Clofibrate treatment significantly increased liver weight; as a result glutathione S-transferase activity (toward 1-chloro-2,4-dinitrobenzene) fell if expressed per gram of liver (4560 +/- 420 (SE) vs 7010 +/- 260 nmoles/min for clofibrate treated and controls respectively, p less than 0.002), but was unchanged when expressed per total liver (60.8 +/- 6.5 vs 64.6 +/- 3.5 mumoles/min for clofibrate and controls p greater than 0.5). Irrespective of how it was expressed fatty acid binding protein was significantly increased by the drug treatment. Steady state sulfobromophthalein-glutathione removal velocity was saturable with increasing concentrations of sulfobromophthalein-glutathione in both control and clofibrate-treated livers. Steady state extraction ratio, as well as Vmax and Km for removal, did not differ between the two groups. In keeping with other observations, these data collectively indicate that the hepatic steady state removal of nonmetabolized compounds is not affected by clofibrate.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of California, San Francisco 94143.
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D
Sorrentino
R A
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Weisiger
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Bass
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V
Licko
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000032:analysis; D002994:Clofibrate / Q000494:pharmacology*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000032:analysis; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013448:Sulfobromophthalein / Q000378:metabolism*
D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D013448:Sulfobromophthalein; D005982:Glutathione Transferase; D005978:Glutathione; D002994:Clofibrate