Validity of using 2,4-3H-labeled bile acids to study bile acid kinetics in man.

Abstract

Abstract [2,2′,4,4′- 3 H]Chenodeoxycholic acid was administered simultaneously with [24- 14 C]chenodeoxycholic acid to 2 healthy subjects, and the 3H14C ratio in bile samples was measured daily for 6 days. This ratio remained identical to that administered, indicating stability of the label. Approximately 12 per cent of administered 3 H entered body water and 5 to 10 per cent was excreted in the urine as 3 H 2 O in 6 days. In similar studies with [2,2′,4,4′- 3 H]cholic acid and[24- 14 C]cholic acid in 3 subjects, biliary cholic acid and deoxycholic acid were isolated chromatographically and the 3H14C ratio of each bile acid was determined. For cholic acid, about 10 per cent of administered 3 H was lost the first day; after that, the 3H14C ratio remained constant. In deoxycholic acid, the 3H14C ratio was 30 to 40 per cent lower than in that administered. Approximately 25 per cent of administered 3 H entered body water, and 8 per cent of the administered dose was excreted in the urine as 3 H 2 O in 6 days. On anaerobic incubation of [2,4- 3 H]cholic and [ 2,4- 3 H ] chenodeoxycholic acids with fresh feces, 20 to 35 per cent of the label was released as 3 H 2 O. Seven out of 24 strains of bacteria tested were capable of releasing 3 H as 3 H 2 O when incubated anaerobically with [2,4- 3 H]cholic acid, but the fraction of 3 H released was much less than that during fecal incubation. Determination of bile acid kinetics in healthy subjects is valid with [2,2′,4,4′- 3 H]chenodeoxycholic acid and has an error of 3 H]cholic acid. However, the 2,2′,4,4′- 3 H label appears unsatisfactory for tracing the complete metabolic fate of the steroid moiety of bile acids in healthy man because 3 H is removed by bacteria during intestinal passage after the labeled bile acids leave the exchangeable bile acid pool.