The Enterohepatic Circulation of Sulfated and Nonsulfated Bile Acids

Abstract

Bile acids are synthesized in the liver from cholesterol and after conjugation with taurine or glycine are excreted into bile. After release in the intestine, the greater part of the bile acids is reabsorbed and returns to the liver via the portal blood stream. In this way bile acids are conserved in an enterohepatic circulation. One of the components of the bile acid pool in man is lithocholate (3αhydroxy-5β-cholanoic acid). This secondary bile acid posesses cholestatic properties which have been well established in experimental animals. Intravenous administration of lithocholate and its taurine or glycine conjugate to rats or hamsters causes a dose-dependent reduction in bile flow (Javitt 1966; Kakis and Yousef 1978; King and Schoenfield 1971). Little is known about the significance of lithocholic acid in the pathogenesis of cholestasis in man. It has been claimed that the human liver is protected from lithocholic acid hepatotoxicity by efficient sulfation of the 3 αhydroxy group, which increases the bile acids’ polarity (Cowen et al. 1975; Marks et al. 1981). Sulfated bile acids are poorly absorbed from the intestine (De Witt and Lack 1980; Low-Beer et al. 1969) and their renal clearance is relatively high (Makino et al. 1975). The hypothesis that sulfation per se might be a protecting factor against hepatotoxic bile acids will be discussed in this chapter.

This work was supported by grant 13-53-44 from the Dutch Health Organization (TNO)