BILE-ACID SYNTHESIS AND BILIARY HYDROPHOBICITY DURING OBSTRUCTIVE-JAUNDICE IN RATS

Hepatic cholesterol 7 alpha-hydroxylase, the rate-lim iting enzyme for bile acid synthesis, is regulated by bile acid returning to the liver . In the bile duct-ligated rats, however, cholesterol 7 alpha-hydroxyl ase activity is known to increase in spite of the elevated serum bile acids. The aim of this study was to investigate the relationship betwe en the bile acid synthesis and biliary hydrophobicity to solve the par adoxical phenomenon. Male Wister rats (250-350 g) were divided into tw o groups, bile duct-ligated group and sham-operated group. Rats were s acrificed on the Days 1, 2, 4, 7, and 14 after the operation. Choleste rol 7 alpha-hydroxylase activity, biliary bile acid composition, and b iliary hydrophobicity were analyzed. Hepatic and serum total bile acid concentrations and serum 7 alpha-hydroxycholesterol levels were also determined. Bile duct ligation caused significant increases in hepatic and serum bile acid concentrations on Day 1, which persisted for 14 d ays after the bile duct ligation. Activities of hepatic cholesterol 7 alpha-hydroxylase increased to 3.2-fold of the preoperative value on D ay 2, remained significantly high until Day 7, and then decreased to t he basal value on Day 14. The serum 7 alpha-hydroxycholesterol level e ssentially behaved in a similar fashion to that of hepatic cholesterol 7 alpha-hydroxylase activity with a significant (P < 0.01) positive c orrelation. beta-Muricholic acid was predominant in bile until Day 7 ( 71 vs 10% in the controls on Day 4; P < 0.05) with a concomitant decre ase in the proportion of cholic acid. Biliary bile acid became less hy drophobic and hepatic cholesterol 7 alpha-hydroxylase activity signifi cantly correlated with the hydrophobicity of biliary bile acids (n = 5 5, r = 0.54, P < 0.01), There were no significant correlations between the activity of cholesterol 7 alpha-hydroxylase and total bile acid c oncentrations in serum, liver, or bile. The increased cholesterol 7 al pha-hydroxylase activity is accompanied by the decreased biliary hydro phobicity, which may be a rationale for the paradoxical increase in bi le acid synthesis in spite of the accumulation of bile acids in the se rum and liver during obstructive jaundice in rats. (C) 1996 Academic P ress, Inc.