Glucuronidation of bile acids by their high-dose infusion into rats

Abstract

We previously reported that high-dose infusion of ursodeoxycholate into rats caused its extensive glucuronidation. In this study, the glucuronidation of various bile acids after high-dose infusion into rats was examined and the effects of coinfusion of bile acids on the glucuronidation of a trace dose of [14C]deoxycholate were also studied. Sixty minutes after infusion of 14C-bile acids at a rate of 1 mumol/min/100 gm, the glucuronidation of the labeled bile acid in the bile was 31%, 15%, 8% and 3% for deoxycholate, ursodeoxycholate, chenodeoxycholate and cholate, respectively. The infusion of a trace dose of [14C] deoxycholate resulted in only 2% glucuronidation, and coinfusion of taurochenodeoxycholate or tauroursodeoxycholate at a rate of 1 mumol/min/100 gm did not change the percentage of glucuronidation of [14C]deoxycholate. However, coinfusion of chenodeoxycholate, ursodeoxycholate or cholate at the same rate markedly increased the percentage of the [14C]deoxycholate-glycuronide in the bile (35%, 18% and 36%, respectively). Thus glucuronidation of bile acids by high-dose infusion into rats occurs predominantly with deoxycholate and is not specific for ursodeoxycholate, and glucuronidation depends on the unconjugated bile acid load, which might be regulated by the capacity of amidation by the liver.