Biliary excretion of sulfated bile acids and organic anions in zone 1- and zone 3-injured rats.
OBJECTIVE
There are several reports on the biliary excretion of bile acids and organic anions in zone 1- and zone 3-injured rat liver, but the results are controversial. In order to dissolve the discrepancy between previous works about the role of hepatic zonation on the hepatic handling of the substrates of multidrug resistance protein 2, the biliary excretion of sulfated bile acids, pravastatin and phenolphthalein glucuronide was studied in zone 1- and zone 3-injured rats.


METHODS
Zone 1 and zone 3 injury were caused by allyl alcohol and bromobenzene, respectively. Bile acid sulfates, pravastatin and phenolphthalein glucuronide were administered i.v. to bile duct-cannulated rats, and their biliary excretion was studied.


RESULTS
The biliary excretion of a tracer dose of taurolithocholate-3-sulfate and its excretory maximum were unchanged in zone 1 injury, but were diminished in zone 3 injury, whereas the biliary excretion of taurochenodeoxycholate-3-sulfate was unchanged in zone 1 and zone 3 injury. The biliary excretion of pravastatin and phenolphthalein glucuronide was markedly decreased only in zone 3 injury, whereas the excretory maximum of phenolphthalein glucuronide was decreased in both zone 1 and zone 3 injury.


CONCLUSIONS
These findings indicate that zone 3 is important for the biliary excretion of substrates of multidrug resistance protein 2.
Sasamoto
Takahiro
T
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Sano
Naoyo
N
Takikawa
Hajime
H
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000838:Anions; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000493:pharmacokinetics*; D001659:Biliary Tract / Q000378:metabolism*; D001692:Biological Transport; D001969:Bromobenzenes; D056486:Chemical and Drug Induced Liver Injury; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010635:Phenolphthaleins / Q000493:pharmacokinetics; D017035:Pravastatin / Q000493:pharmacokinetics; D020005:Propanols; D051381:Rats; D017207:Rats, Sprague-Dawley; D013658:Taurolithocholic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics
D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D000838:Anions; D001647:Bile Acids and Salts; D001969:Bromobenzenes; D010635:Phenolphthaleins; D020005:Propanols; C016651:phenolphthalein glucuronide; C066776:taurolithocholic acid 3-sulfate; C006463:allyl alcohol; D013658:Taurolithocholic Acid; C032036:bromobenzene; D017035:Pravastatin