Effects of cholic acid, 7β-hydroxy- and 12β-hydroxy-isocholic acid on bile flow, lipid secretion and bile acid synthesis in the rat

Abstract

The effects of three epimeric trihydroxy-cholanoic acids, cholic acid (C), 7β-hydroxy-(7β) and 12β-hydroxy-(12β) isocholic acids on bile flow, lipid secretion, bile synthesis and bile micellar properties were studied in the rat with a bile fistula. The bile salts were infused intraduodenally starting 72 hours after cannulation when endogeneous bile salt synthesis had plateaued after the bile salt pool was drained. The bile salts were infused at two levels 2 and 4 μmol min⁻¹ kg⁻¹. All three bile salts were absorbed and secreted almost quantitatively into the bile. Cholic acid was secreted in the conjugated form, 7β conjugated to -60% and 12|3 completely in the unconjugated form. The bile salts did not undergo any significant biotransformations during the one passage from the intestine through the liver. Bile flow increased from the preinfusion level for all three bile salts infused in the order 7β> 12β>C. The bile flow increased linearly with bile salt secretion more for 7β than for C and 12β. Infusion of C increased the secretion into bile of phospholipid (PL) and cholesterol (CH) over the preinfusion values. Infusion of 7β as well as 12β resulted in a parallel decrease in the secretion of PL as well as CH compared to the preinfusion values. The infusion of C and 7β at the two levels used decreased the secretion of newly synthesized bile salt below the control level. After infusion of 12β the rate of secretion of newly synthesized bile salt doubled.

The content of mixed bile salt micelles in the bile secreted after infusion of the high critical micellar concentration (CMC) 7β and 12β was low compared to that seen after C. These biles also showed a limited capacity to dissolve PL in mixed micellar solution.

Key Words:

• bile fistula
• bile lipids
• bile salt micelles
• equilibrium dialysis
• ursocholic acid