Abstrakt: |
To further clarify the relationship between physical-chemical characteristics of bile acids and biliary lipid secretion, we investigated the effect of ursocholic acid, the 7β-hydroxyepimer of cholic acid, on bile lipid secretion and composition. The study included (a) acute duodenal infusion (1 g/h for 5 h) of ursocholic acid contrasted with a less hydrophilic bile acid, ursodeoxycholic acid, in 3 T-tube patients and (b) short-term oral administration (2 wk) of ursocholic acid (10–15 mg/kg · day) to 10 gallstone patients. Following acute infusion, ursocholic acid, similarly to ursodeoxycholic acid, accounted for >80% of the biliary bile acids. However, ursocholic acid induced (per micromole of secreted bile acid) a significantly lower (p < 0.01) secretion of cholesterol (0.013 μmol) and phospholipids (0.054 μmol) than that induced by ursodeoxycholic acid (0.034 μmol of cholesterol and 0.138 μmol of phospholipids). Biliary alkaline phosphatase activity during ursocholic acid administration was significantly lower (p < 0.01) than during ursodeoxycholic acid administration. After short-term oral administration, ursocholic acid, undetectable before treatment, constituted 20.50% ± 8.60% of the biliary bile acids. The percentage of deoxycholic acid increased from 32.35% ± 18.79% to 47.53% ± 16.19% (p < 0.05). Mean saturation index decreased from a pretreatment value of 1.23 ± 0.22 to 0.99 ± 0.17 (p < 0.05), but only in 4 of 10 subjects did bile become undersaturated. It is concluded that ursocholic acid, due to its higher hydrophilicity, stimulates a lower cholesterol and phospholipid output than ursodeoxycholic acid. Consequently, despite the low enrichment of the biliary bile acids with ursocholic acid, oral administration of ursocholic acid induces a reduction of bile cholesterol saturation. |