Reversibility of organic anion-induced cholestasis: association with compensatory hypersecretion of biliary phospholipid and protein in the dog

• Published in: Journal of gastroenterology and hepatology Vol. 9; no. 1; p. 35
• Main Authors: Tazuma, S, Tokumo, H, Yamashita, G, Horikawa, K, Miura, H, Hirano, N, Aihara, N, Sasaki, M, Teramen, K, Ochi, H
• Format: Journal Article
• Language: English
• Published: Australia 01.01.1994
• Subjects: Animals; Anions; Bile - metabolism; Cholestasis - chemically induced; Cholestasis - physiopathology; Dehydrocholic Acid - pharmacology; Dogs; Dose-Response Relationship, Drug; Drug Synergism; Female; Phospholipids - metabolism; Proteins - metabolism; Rose Bengal; Sulfobromophthalein; Taurocholic Acid - pharmacology
• ISSN: 0815-9319
• DOI: 10.1111/j.1440-1746.1994.tb01213.x

The effect of a concomitant infusion of organic anions, structurally related phthaleins, on bile flow was studied in anaesthetized dogs. A combination of rose bengal and sulfobromophthalein was found to uniquely and synergistically produce an acute, reversible form of intrahepatic cholestasis (< 10% of control level). This phenomenon was not observed with the administration of those individual organic anions at concentrations previously associated with the induction of intrahepatic cholestasis. The infusion of either a micelle forming bile salt, sodium taurocholate, or a non-micelle forming bile salt, sodium dehydrocholate, rapidly reversed the intrahepatic cholestasis (within 20 min after bile salt infusion). During the choleretic phase immediately following the bile salt infusion, a transient but marked hypersecretion, a disproportionately increased output in relation to that of bile acids, of biliary phospholipid (176% of control level by taurocholate and 138% of control level by dehydrocholate), and an even more striking amount of biliary protein hypersecretion were observed (392% of control level by taurocholate and 357% of control level by dehydrocholate). Although the significance of these new post-cholestatic observations requires clarification, it is suggested that the intrahepatic cholestasis induced by organic anions reflects a reversible defect in the mechanism(s) involved in transcellular transport.