The bile flow and biliary excretion of ursocholate in the rat

Several studies reported that ursodeoxycholate (but not its conjugates), when administered intravenously, increased the biliary bicarbonate concentration in the rat (1–3). At the same time, a complete dissociation between bile flow and the bile salt excretion rate was produced in the second hr of infusion (2). In order to examine whether this property was due to the 7β-hydroxy group in its molecular structure, the choleretic property of ursocholate (3α, 7β, 12α-trihydroxy-5β-cholanoic acid) was investigated in male Wistar rats. Immediately after the start of iv infusion of ursocholate at a rate of 1.2 μmole/min/100 g b. wt., both the bile flow and bile salt excretion rate began to increase. However, unlike with ursodeoxycholate, the bile salt excretion rate continued to be high in the second and third hr of infusion, while the bile flow rate gradually increased. Furthermore, the bicarbonate concentration in the bile fell slightly 10 min after the start of ursocholate infusion. Although the concentration tended to return to the baseline value before the bile salt infusion in the later period of observation, no significant increase in bicarbonate concentration was observed during the whole observation period. These properties were quite similar to those of cholate rather than those of ursodeoxycholate. However, a cholate infusion at the same rate of 1.2 μmole/min/100 g b.wt. caused a cholestasis as early as 20 to 30 min after the start of an infusion. These results suggest that the previously reported properties of ursodeoxycholate (that it causes a complete dissociation between the bile flow and bile salt excretion rate in the second hr and that it increases the biliary bicarbonate concentration) were not due to the 7β-hydroxy group in its steroidal structure, and that the choleretic property of ursocholate is similar to its 7α-hydroxy epimar, cholate. However, the much lower cytotoxicity of ursocholate compared to cholate appears to be due to the 7β-hydroxy group that ursocholate has.