Biliary excretion of bile acids and organic anions in rats with dichloroethylene-induced bile canalicular injury

Abstract

Hepatocytes in zone 1 of the hepatic lobule play a role in the uptake and biliary excretion of bile acids and organic anions under physiological conditions, and hepatocytes in zone 3 may play a role only when there is a high-dose load. To further elucidate the role of hepatic zonation in the hepatic handling of bile acids and organic anions, the biliary excretion of these compounds was studied in rats with dichloroethylene (DCE)-induced selective zone 3 bile canalicular injury. Biliary excretion of various bile acids and organic anions was studied in rats 1 h after oral administration of DCE (5 mg/100 g). The effect of DCE on the immunostaining of multidrug resistance protein 2 (Mrp2; an important canalicular organic anion transporter) in the liver was also examined. The biliary excretory maximum of taurocholate and tauroursodeoxycholate was decreased in DCE-treated rats, whereas the biliary excretion of taurolithocholate-sulfate and phenolphthalein-glucuronide was unchanged in DCE-treated rats, and DCE treatment decreased the biliary excretion of sulfobromophthalein and pravastatin. DCE decreased Mrp2 staining in the canalicular membrane of zone 3 hepatocytes on immunohistochemistry. These findings indicate that canalicular transport in zone 3 hepatocytes is important in the biliary excretion of bile acids and organic anions, when they are administered at high doses.