Reversibility of organic anion-induced cholestasis: association with compensatory hypersecretion of biliary phospholipid and protein in the dog.
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.
Tazuma
S
S
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Tokumo
H
H
Yamashita
G
G
Horikawa
K
K
Miura
H
H
Hirano
N
N
Aihara
N
N
Sasaki
M
M
Teramen
K
K
Ochi
H
H
D000818:Animals; D000838:Anions; D001646:Bile / Q000378:metabolism*; D002779:Cholestasis / Q000139:chemically induced* / Q000503:physiopathology*; D003685:Dehydrocholic Acid / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D010743:Phospholipids / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012395:Rose Bengal; D013448:Sulfobromophthalein; D013656:Taurocholic Acid / Q000494:pharmacology
D000838:Anions; D010743:Phospholipids; D011506:Proteins; D013448:Sulfobromophthalein; D012395:Rose Bengal; D013656:Taurocholic Acid; D003685:Dehydrocholic Acid