Transport of chenodeoxycholic acid and its 3-α- and 7-α-sulfates by isolated perfused rat liver

Ulrich Gärtner, Tobias Goeser, Adolf Stiehl, Richard Raedsch, Allan W. Wolkoff

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

In patients with cholestasis, levels of sulfated bile acids rise. Sulfate esters of chenodeoxycholic acid are the most abundant of these bile acid sulfates. These compounds are taken up by the liver and excreted into bile, although their plasma clearance and biliary excretion are reduced compared with that of unsulfated bile acids. It is not clear whether this is due to differences in intrinsic hepatic uptake or biliary excretion. In the present study, single-pass transport kinetics of chenodeoxycholic acid 3-α-sulfate, chenodeoxycholic acid 7-α-sulfate and unsulfated chenodeoxycholic acid were quantified in isolated perfused rat liver. Influx of the 7-α- and 3-α-sulfated derivatives was 57% and 20% that of chenodeoxycholic acid, respectively. These three compounds bound to albumin equally well, indicating that this was not a factor in their differential uptake. Although single-pass extraction of each of these compounds differed, biliary excretion of material taken up by the liver was identical. There was no difference in bile flow or biliary excretion rate, regardless of which bile acid sulfate was tested. These results indicate that the low plasma elimination of sulfated bile acids previously observed by others can be explained by low hepatic influx. The diminished transport into liver resulting from sulfation could lead to enhanced elimination of bile acids by the kidney.

Original languageEnglish (US)
Pages (from-to)738-742
Number of pages5
JournalHepatology
Volume12
Issue number4
StatePublished - Oct 1990

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Chenodeoxycholic Acid
Sulfates
Bile Acids and Salts
Liver
Bile
Cholestasis
Albumins
Esters
Hepatobiliary Elimination
Kidney

ASJC Scopus subject areas

  • Hepatology

Cite this

Transport of chenodeoxycholic acid and its 3-α- and 7-α-sulfates by isolated perfused rat liver. / Gärtner, Ulrich; Goeser, Tobias; Stiehl, Adolf; Raedsch, Richard; Wolkoff, Allan W.

In: Hepatology, Vol. 12, No. 4, 10.1990, p. 738-742.

Research output: Contribution to journalArticle

Gärtner, U, Goeser, T, Stiehl, A, Raedsch, R & Wolkoff, AW 1990, 'Transport of chenodeoxycholic acid and its 3-α- and 7-α-sulfates by isolated perfused rat liver', Hepatology, vol. 12, no. 4, pp. 738-742.
Gärtner, Ulrich ; Goeser, Tobias ; Stiehl, Adolf ; Raedsch, Richard ; Wolkoff, Allan W. / Transport of chenodeoxycholic acid and its 3-α- and 7-α-sulfates by isolated perfused rat liver. In: Hepatology. 1990 ; Vol. 12, No. 4. pp. 738-742.
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AB - In patients with cholestasis, levels of sulfated bile acids rise. Sulfate esters of chenodeoxycholic acid are the most abundant of these bile acid sulfates. These compounds are taken up by the liver and excreted into bile, although their plasma clearance and biliary excretion are reduced compared with that of unsulfated bile acids. It is not clear whether this is due to differences in intrinsic hepatic uptake or biliary excretion. In the present study, single-pass transport kinetics of chenodeoxycholic acid 3-α-sulfate, chenodeoxycholic acid 7-α-sulfate and unsulfated chenodeoxycholic acid were quantified in isolated perfused rat liver. Influx of the 7-α- and 3-α-sulfated derivatives was 57% and 20% that of chenodeoxycholic acid, respectively. These three compounds bound to albumin equally well, indicating that this was not a factor in their differential uptake. Although single-pass extraction of each of these compounds differed, biliary excretion of material taken up by the liver was identical. There was no difference in bile flow or biliary excretion rate, regardless of which bile acid sulfate was tested. These results indicate that the low plasma elimination of sulfated bile acids previously observed by others can be explained by low hepatic influx. The diminished transport into liver resulting from sulfation could lead to enhanced elimination of bile acids by the kidney.

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