The ursodeoxycholate dose-dependent formation of ursodeoxycholate-glucuronide in the rat and the choleretic potencies

The reason for the discrepancy between bile flow and biliary bile acid excretion during ursodeoxycholate infusion in rats is unknown. We found that ursodeoxycholate-glucuronide is formed during ursodeoxycholate infusion at higher doses. Ursodeoxycholate infusion (1 to 3 mumol/min/100 gm body weight) for 90 min caused marked hypercholeresis, and the previously reported discrepancy between bile flow and biliary bile acid excretion was observed when bile acid concentrations were measured by regular enzymatic methods. However, the appearance of ursodeoxycholate-glucuronide was observed on thin-layer chromatography analysis and up to 30% of the ursodeoxycholate in bile was found to be glucuronidated when determined by the enzymatic method after beta-glucuronidase treatment. The choleretic activity of ursodeoxycholate-glucuronide (25.2 microliters/mumol) was about 3 times higher than that of ursodeoxycholate (8.9 microliters/mumol) when infused at 0.25 mumol/min/100 gm body weight and ursodeoxycholate-glucuronide also stimulated higher biliary bicarbonate excretion than ursodeoxycholate. These results indicate that the discrepancy between bile flow and biliary bile acid excretion caused by high-dose infusion of ursodeoxycholate into rats can be explained by glucuronide conjugation of ursodeoxycholate that cannot be detected by the regular enzymatic method. The glucuronidation of ursodeoxycholate might also be important in the ursodeoxycholate-induced increase in biliary bicarbonate excretion.