Hypocholesterolemic Effect of Bile Acid Sulfonate Analogs in Hamsters.

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  • KIM Hyun-Guell
    Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine and Department of Biochemistry
  • UNE Mizuho
    Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine and Department of Biochemistry
  • KURAMOTO Taiju
    Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine and Department of Biochemistry
  • NOSHIRO Mitsuhide
    Hiroshima University School of Dentistry
  • FUJIMURA Kingo
    Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine and Department of Biochemistry

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説明

We studied the effects of bile acid sulfonate analogs, namely, 3α,7α,12α-trihydroxy-5β-cholane-24-sulfonate (C-sul), 3α,7α-dihydroxy-5β-cholane-24-sulfonate (CDC-sul), and 3α,7β-dihydroxy-5β-cholane-24-sulfonate (UDC-sul), on serum and liver cholesterol levels, cholesterol 7α-hydroxylase activity, and biliary bile acid composition in hamsters fed cholesterol. Of the three analogs studied, UDC-sul slightly but significantly decreased free, esterified, and total cholesterol concentrations in the serum. UDC-sul and CDC-sul reduced liver total cholesterol levels by 25% and 18%, respectively, particularly in the esterified cholesterol fraction. Analysis of biliary bile acids showed the presence of the administered analogs, indicating that sulfonate analogs efficiently participate in enterohepatic cycling. The proportion of cholic acid was increased in all groups fed sulfonate analogs, but the ratio of glycine to taurine conjugated bile acids (G/T) was elevated only in UDC-sul feeding hamsters. There was no significant change in cholesterol 7α-hydroxylase activity in hamsters fed C-sul or CDC-sul, while UDC-sul slightly stimulated the enzyme activity compared to the control. The UDC-sul induced decrease in serum and liver cholesterol concentrations may be secondary to enhanced bile acid synthesis. This is supported by the increased cholesterol 7α-hydroxylase activity and elevated G/T ratio in biliary bile acids observed following UDC-sul administration.

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