Bile acid synthesis and biliary hydrophobicity during obstructive jaundice in rats

Hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme for bile acid synthesis, is regulated by bile acid returning to the liver. In the bile duct-ligated rats, however, cholesterol 7alpha-hydroxylase activity is known to increase in spite of the elevated serum bile acids. The aim of this study was to investigate the relationship between the bile acid synthesis and biliary hydrophobicity to solve the paradoxical phenomenon. Male Wister rats (250-350 g) were divided into two groups, bile duct-ligated group and sham-operated group. Rats were sacrificed on the Days 1, 2, 4, 7, and 14 after the operation. Cholesterol 7alpha-hydroxylase activity, biliary bile acid composition, and biliary hydrophobicity were analyzed. Hepatic and serum total bile acid concentrations and serum 7alpha-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 days after the bile duct ligation. Activities of hepatic cholesterol 7alpha-hydroxylase increased to 3.2-fold of the preoperative value on Day 2, remained significantly high until Day 7, and then decreased to the basal value on Day 14. The serum 7alpha-hydroxycholesterol level essentially behaved in a similar fashion to that of hepatic cholesterol 7alpha-hydroxylase activity with a significant (P < 0.01) positive correlation. 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 decrease in the proportion of cholic acid. Biliary bile acid became less hydrophobic and hepatic cholesterol 7alpha-hydroxylase activity significantly correlated with the hydrophobicity of biliary bile acids (n = 55, r = 0.54, P < 0.01). There were no significant correlations between the activity of cholesterol 7alpha-hydroxylase and total bile acid concentrations in serum, liver, or bile. The increased cholesterol 7alpha-hydroxylase activity is accompanied by the decreased biliary hydrophobicity, which may be a rationale for the paradoxical increase in bile acid synthesis in spite of the accumulation of bile acids in the serum and liver during obstructive jaundice in rats.