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  • Title: Influence of bezafibrate on hepatic cholesterol metabolism in gallstone patients: reduced activity of cholesterol 7 alpha-hydroxylase.
    Author: Ståhlberg D, Reihnér E, Rudling M, Berglund L, Einarsson K, Angelin B.
    Journal: Hepatology; 1995 Apr; 21(4):1025-30. PubMed ID: 7705775.
    Abstract:
    Bezafibrate is a hypolipidemic fibric acid derivative known to induce cholesterol supersaturation of bile. To characterize its effects on hepatic cholesterol metabolism, 31 normolipidemic, normal-weight patients with gallstones undergoing cholecystectomy were studied. Eleven patients (5 men) were randomized to treatment with bezafibrate, 200 mg three times daily for 4 weeks before operation; the remaining 20 patients (5 men) served as nontreatment controls. At operation, a liver biopsy specimen was obtained under standardized conditions and several important parameters of cholesterol metabolism were assayed. Bezafibrate treatment lowered total plasma cholesterol and triglycerides 30% and 37%, respectively. The hepatic cholesterol 7 alpha-hydroxylase activity was reduced by approximately 60% in the bezafibrate treated patients compared with the controls, whereas the acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity was similar in the two groups. The total 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity was increased twofold in the treated patients, whereas the active enzyme remained about the same as in the controls. The low-density lipoprotein (LDL) receptor binding activity was unaffected by the treatment. Bezafibrate treatment significantly reduces cholesterol 7 alpha-hydroxylase activity, and it is suggested that this may play an important role for the development of supersaturated bile during such therapy.
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