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

Nicholas F La Russo, Neville E. Hoffman, Alan F. Hofmann

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

[2,2′,4,4′-3H]Chenodeoxycholic acid was administered simultaneously with [24-14C]chenodeoxycholic acid to 2 healthy subjects, and the 3H 14C 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 3H entered body water and 5 to 10 per cent was excreted in the urine as 3H2O in 6 days. In similar studies with [2,2′,4,4′-3H]cholic acid and[24-14C]cholic acid in 3 subjects, biliary cholic acid and deoxycholic acid were isolated chromatographically and the 3H 14C ratio of each bile acid was determined. For cholic acid, about 10 per cent of administered 3H was lost the first day; after that, the 3H 14C ratio remained constant. In deoxycholic acid, the 3H 14C ratio was 30 to 40 per cent lower than in that administered. Approximately 25 per cent of administered 3H entered body water, and 8 per cent of the administered dose was excreted in the urine as 3H2O in 6 days. On anaerobic incubation of [2,4-3H]cholic and [ 2,4-3H ] chenodeoxycholic acids with fresh feces, 20 to 35 per cent of the label was released as 3H2O. Seven out of 24 strains of bacteria tested were capable of releasing 3H as 3H2O when incubated anaerobically with [2,4-3H]cholic acid, but the fraction of 3H released was much less than that during fecal incubation. Determination of bile acid kinetics in healthy subjects is valid with [2,2′,4,4′-3H]chenodeoxycholic acid and has an error of < 10 per cent with [2,2′,4,4′-3H]cholic acid. However, the 2,2′,4,4′-3H label appears unsatisfactory for tracing the complete metabolic fate of the steroid moiety of bile acids in healthy man because 3H is removed by bacteria during intestinal passage after the labeled bile acids leave the exchangeable bile acid pool.

Original languageEnglish (US)
Pages (from-to)759-765
Number of pages7
JournalThe Journal of Laboratory and Clinical Medicine
Volume84
Issue number5
StatePublished - 1974

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Cholic Acid
Bile Acids and Salts
Chenodeoxycholic Acid
Kinetics
Labels
Deoxycholic Acid
Body Water
Bacteria
Healthy Volunteers
Urine
Water
Feces
Bile
Steroids

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Validity of using 2,4-3H-labeled bile acids to study bile acid kinetics in man. / La Russo, Nicholas F; Hoffman, Neville E.; Hofmann, Alan F.

In: The Journal of Laboratory and Clinical Medicine, Vol. 84, No. 5, 1974, p. 759-765.

Research output: Contribution to journalArticle

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abstract = "[2,2′,4,4′-3H]Chenodeoxycholic acid was administered simultaneously with [24-14C]chenodeoxycholic acid to 2 healthy subjects, and the 3H 14C 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 3H entered body water and 5 to 10 per cent was excreted in the urine as 3H2O in 6 days. In similar studies with [2,2′,4,4′-3H]cholic acid and[24-14C]cholic acid in 3 subjects, biliary cholic acid and deoxycholic acid were isolated chromatographically and the 3H 14C ratio of each bile acid was determined. For cholic acid, about 10 per cent of administered 3H was lost the first day; after that, the 3H 14C ratio remained constant. In deoxycholic acid, the 3H 14C ratio was 30 to 40 per cent lower than in that administered. Approximately 25 per cent of administered 3H entered body water, and 8 per cent of the administered dose was excreted in the urine as 3H2O in 6 days. On anaerobic incubation of [2,4-3H]cholic and [ 2,4-3H ] chenodeoxycholic acids with fresh feces, 20 to 35 per cent of the label was released as 3H2O. Seven out of 24 strains of bacteria tested were capable of releasing 3H as 3H2O when incubated anaerobically with [2,4-3H]cholic acid, but the fraction of 3H released was much less than that during fecal incubation. Determination of bile acid kinetics in healthy subjects is valid with [2,2′,4,4′-3H]chenodeoxycholic acid and has an error of < 10 per cent with [2,2′,4,4′-3H]cholic acid. However, the 2,2′,4,4′-3H label appears unsatisfactory for tracing the complete metabolic fate of the steroid moiety of bile acids in healthy man because 3H is removed by bacteria during intestinal passage after the labeled bile acids leave the exchangeable bile acid pool.",
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N2 - [2,2′,4,4′-3H]Chenodeoxycholic acid was administered simultaneously with [24-14C]chenodeoxycholic acid to 2 healthy subjects, and the 3H 14C 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 3H entered body water and 5 to 10 per cent was excreted in the urine as 3H2O in 6 days. In similar studies with [2,2′,4,4′-3H]cholic acid and[24-14C]cholic acid in 3 subjects, biliary cholic acid and deoxycholic acid were isolated chromatographically and the 3H 14C ratio of each bile acid was determined. For cholic acid, about 10 per cent of administered 3H was lost the first day; after that, the 3H 14C ratio remained constant. In deoxycholic acid, the 3H 14C ratio was 30 to 40 per cent lower than in that administered. Approximately 25 per cent of administered 3H entered body water, and 8 per cent of the administered dose was excreted in the urine as 3H2O in 6 days. On anaerobic incubation of [2,4-3H]cholic and [ 2,4-3H ] chenodeoxycholic acids with fresh feces, 20 to 35 per cent of the label was released as 3H2O. Seven out of 24 strains of bacteria tested were capable of releasing 3H as 3H2O when incubated anaerobically with [2,4-3H]cholic acid, but the fraction of 3H released was much less than that during fecal incubation. Determination of bile acid kinetics in healthy subjects is valid with [2,2′,4,4′-3H]chenodeoxycholic acid and has an error of < 10 per cent with [2,2′,4,4′-3H]cholic acid. However, the 2,2′,4,4′-3H label appears unsatisfactory for tracing the complete metabolic fate of the steroid moiety of bile acids in healthy man because 3H is removed by bacteria during intestinal passage after the labeled bile acids leave the exchangeable bile acid pool.

AB - [2,2′,4,4′-3H]Chenodeoxycholic acid was administered simultaneously with [24-14C]chenodeoxycholic acid to 2 healthy subjects, and the 3H 14C 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 3H entered body water and 5 to 10 per cent was excreted in the urine as 3H2O in 6 days. In similar studies with [2,2′,4,4′-3H]cholic acid and[24-14C]cholic acid in 3 subjects, biliary cholic acid and deoxycholic acid were isolated chromatographically and the 3H 14C ratio of each bile acid was determined. For cholic acid, about 10 per cent of administered 3H was lost the first day; after that, the 3H 14C ratio remained constant. In deoxycholic acid, the 3H 14C ratio was 30 to 40 per cent lower than in that administered. Approximately 25 per cent of administered 3H entered body water, and 8 per cent of the administered dose was excreted in the urine as 3H2O in 6 days. On anaerobic incubation of [2,4-3H]cholic and [ 2,4-3H ] chenodeoxycholic acids with fresh feces, 20 to 35 per cent of the label was released as 3H2O. Seven out of 24 strains of bacteria tested were capable of releasing 3H as 3H2O when incubated anaerobically with [2,4-3H]cholic acid, but the fraction of 3H released was much less than that during fecal incubation. Determination of bile acid kinetics in healthy subjects is valid with [2,2′,4,4′-3H]chenodeoxycholic acid and has an error of < 10 per cent with [2,2′,4,4′-3H]cholic acid. However, the 2,2′,4,4′-3H label appears unsatisfactory for tracing the complete metabolic fate of the steroid moiety of bile acids in healthy man because 3H is removed by bacteria during intestinal passage after the labeled bile acids leave the exchangeable bile acid pool.

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