Fibrates modify the expression of key factors involved in bile-acid synthesis and biliary-lipid secretion in gallstone patients
| Autor: | Núria Roglans, Ferran Novell, Marta Alegret, Manuel Vázquez-Carrera, Rosa M. Sánchez, Daniel Zambón, Emilio Ros, Juan C. Laguna |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Down-Regulation Gallstones Fibrate Biology Cholesterol 7 alpha-hydroxylase Bile Acids and Salts Fenofibrate Downregulation and upregulation Internal medicine medicine Humans Gemfibrozil Pharmacology (medical) Secretion Cholesterol 7-alpha-Hydroxylase skin and connective tissue diseases Hypolipidemic Agents Pharmacology Bezafibrate Reverse Transcriptase Polymerase Chain Reaction Cholesterol LDL General Medicine Middle Aged Lipid Metabolism medicine.disease Endocrinology Female lipids (amino acids peptides and proteins) sense organs medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 59:855-861 |
| ISSN: | 1432-1041 0031-6970 |
| DOI: | 10.1007/s00228-003-0704-1 |
| Popis: | Fibrate treatment induces adverse changes in biliary-lipid and bile-acid composition. Since the molecular mechanisms underlying these changes are still unclear, we have investigated the effect of fibrate treatment on key factors involved in bile-acid synthesis, biliary-lipid secretion and cholesterol metabolism in gallstone patients.Patients with uncomplicated gallstones and a serum level of low-density lipoprotein (LDL) cholesterol130 mg/dl were randomly assigned to open-label treatment with bezafibrate, fenofibrate, gemfibrozil, or placebo for 8 weeks before elective cholecystectomy. A liver specimen was obtained at operation, and the mRNA relative levels for cholesterol 7alpha-hydroxylase (CYP7A1), hepatocyte nuclear factor-4 (HNF-4), ATP-binding cassette transporters MDR3, ABCG5, and ABCG8, human homologue scavenger receptor BI, sterol response element binding protein-2 (SREBP-2), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and LDL receptor were determined by means of reverse-transcriptase polymerase chain reaction.Bezafibrate, fenofibrate and gemfibrozil significantly reduced CYP7A1 mRNA levels. The three fibrates tested raised the mRNA levels of ABCG5 and SREBP-2, but only bezafibrate induced significant changes. Although MDR-3 mRNA levels were slightly increased by the three fibrates, no significant differences were obtained.These results show for the first time that fibrate administration to humans downregulates CYP7A1. Although ABCG5 and SREBP-2 mRNA levels were slightly increased by all treatment groups, only bezafibrate induced significant changes. |
| Databáze: | OpenAIRE |
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