Bile acid sulfonate and 7-alkylated bile acid analogs:: Effect on intestinal absorption of taurocholate and cholesterol 7α-hydroxylase activity in cultured rat hepatocytes

• Published in: Steroids Vol. 65; no. 1; pp. 24 - 28
• Main Authors: Kim, Hyun-Guell, Une, Mizuho, Hino, Akinobu, Wada, Hiroko, Yoshii, Michiko, Kuramoto, Taiju, Fujimura, Kingo
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 2000; Elsevier; Elsevier Science
• Subjects: Bile acid analogs; Bile acids; Biochemistry & Molecular Biology; Biological and medical sciences; Cholesterol 7α-hydroxylase; Cultured hepatocytes; Endocrinology & Metabolism; Fundamental and applied biological sciences. Psychology; Intestinal absorption; Life Sciences & Biomedicine; Liver. Bile. Biliary tracts; Science & Technology; Vertebrates: digestive system; Cholesterol 7α-hydroxylase; Bile acids; Intestinal absorption; Bile acid analogs; Cultured hepatocytes; cultured hepatocytes; cholesterol 7 alpha-hydroxylase; URSODEOXYCHOLIC ACID; MESSENGER-RNA; METABOLISM; bile acids; HAMSTERS; bile acid analogs; intestinal absorption; CHENODEOXYCHOLIC ACID; SALTS; Rat; Digestive system; Enzyme; Liver; Rodentia; Gut; In vitro; Vertebrata; Mammalia; Absorption; Enzymatic activity; Hepatocyte; Bile acid; Analog; Oxidoreductases; Cholesterol 7α-monooxygenase
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/S0039-128X(99)00075-6

The effects of sulfonate analogs of cholic (C), chenodeoxycholic (CDC), and ursodeoxycholic acid (UDC) and three 7-alkylated CDCs—7-methyl-, 7-ethyl-, and 7-propyl-CDCs—on taurocholate absorption from rat terminal ileum in situ and on cholesterol 7α-hydroxylase activity in primary culture of the rat liver were investigated. The sulfonate analogs of two dihydroxy bile acids CDC and UDC, but not C, significantly decreased the absorption of taurocholate. Taurine conjugates of 7-alkylated CDC slightly decreased the taurocholate absorption, and tauro-7-propyl-CDC significantly suppressed the absorption. Although the sulfonate analogs of C and CDC reduced cholesterol 7α-hydroxylase activity by 40% and 60% compared to control, UDC-sulfonate analog did not affect enzymatic activity. These results were consistent with those of the lead compounds, C, CDC, and UDC. The introduction of methyl group at C-7 position of CDC attenuated the reduction in cholesterol 7α-hydroxylase activity by CDC. However, elongation of the alkyl group resulted in an inhibitory effect. The present study revealed the following: 1) bile acid sulfonates act on cholesterol and bile acid metabolism in a similar manner as taurine conjugated bile acids; and 2) the biologic properties of CDC could be altered by the introduction of alkyl group at C-7 position.