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

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 s itu and on cholesterol 7 alpha-hydroxylase activity in primary culture of t he rat liver were investigated. The sulfonate analogs of two dihydroxy bile acids CDC and UDC, but not C, significantly decreased the absorption of ta urochalate. Taurine conjugates of 7-alkylated CDC slightly decreased the ta urocholate absorption, and tauro-7-propyl-CDC significantly suppressed the absorption. Although the sulfonate analogs of C and CDC reduced cholesterol 7 alpha-hydroxylase activity by 40% and 60% compared to control, UDC-sulfo nate analog did not affect enzymatic activity. These results were consisten t with those of the lead compounds, C, CDC, and UDC. The introduction of me thyl group at C-7 position of CDC attenuated the reduction in cholesterol 7 alpha-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 s imilar manner as taurine conjugated bile acids; and 2) the biologic propert ies of CDC could be altered by the introduction of alkyl group at C-7 posit ion. (C) 2000 Elsevier Science Inc. All rights reserved.