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Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion
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  1. T Sudhop,
  2. Y Sahin,
  3. B Lindenthal,
  4. C Hahn,
  5. C Lüers,
  6. H K Berthold,
  7. K von Bergmann
  1. Department of Clinical Pharmacology, University of Bonn, Germany
  1. Correspondence to:
    Dr K von Bergmann, Department of Clinical Pharmacology, Sigmund-Freud-Str 25, 53105 Bonn, Germany;
    vonbergmann{at}uni-bonn.de

Abstract

Background: Recently identified ABCG5/8 transporters are responsible in part for the different absorption rates of campesterol, sitosterol, and cholesterol. These transporters are also expressed in the liver and might regulate biliary sterol secretion.

Aims: This study was therefore conducted to determine the biliary secretion rates and hepatic clearances of campesterol, sitosterol, and cholesterol.

Subjects: Six healthy, male volunteers.

Methods: Deuterium labelled sitosterol and campesterol, and unlabelled sitostanol were constantly infused together with a liquid formula using a duodenal perfusion technique. Biliary secretion and hepatic clearance rates were calculated from hourly bile and plasma samples.

Results: Plasma concentrations of cholesterol, campesterol, and sitosterol averaged 167.5 (50) mg/dl (SD), 0.50 (0.22) mg/dl, and 0.30 (0.10) mg/dl, respectively. Sitosterol showed a significantly higher biliary secretion rate (1.23 (0.87) mg/h) than campesterol (0.76 (0.54) mg/h, p=0.0321), but both plant sterols had significantly lower biliary secretion rates compared with cholesterol (47.7 (17.5) mg/h; p=0.001 for both). Hepatic clearance of cholesterol (0.31 (0.18) dl/h) was significantly lower compared with campesterol (2.11 (2.51) dl/h) and sitosterol (4.97 (4.70) dl/h; p=0.028 for both), and the clearance of campesterol was significant lower compared with sitosterol (p=0.028).

Conclusion: The observed inverse relation between hepatic clearance and known intestinal absorption of cholesterol, campesterol, and sitosterol supports the hypothesis that the ABCG5/8 transporters regulating intestinal sterol absorption might also be involved in biliary sterol excretion.

  • plant sterols
  • cholesterol
  • campesterol
  • sitosterol
  • biliary excretion
  • hepatic clearance
  • ABCG5/8

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