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Effects of pravastatin and bezafibrate on biliary lipid excretion and hepatic expression of Abcg5 and Abcg8 in the rat.

Abstract：

BACKGROUND AND AIM:Multidrug resistance associated gene product 2 (Mdr2) is believed to have a significant role in biliary cholesterol and phospholipid secretions. Both pravastatin and bezafibrate resulted in Mdr2 induction, but increased cholesterol secretion was observed only in pravastatin treatment. To explore the mechanism, the hepatic expression of genes that are responsible for the metabolism of the lipids was studied. METHODS:Rats were divided into three experimental groups: (i) the control group; (ii) the bezafibrate group, which was fed a diet containing 0.45% bezafibrate for 5 days; and (iii) the pravastatin group, which was fed a diet containing 0.1% pravastatin for 5 days. Serum, hepatic and biliary lipids were measured by colorimetric assays and hepatic mRNA related to lipid metabolism was studied by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:In the bezafibrate group biliary phospholipid secretion was increased although cholesterol secretion was not increased. In the pravastatin group, biliary cholesterol and phospholipid secretions were significantly increased. The biliary cholesterol/phospholipid ratio was decreased in the bezafibrate group, but the ratio did not change in the pravastatin group. Hepatic Mdr2, Abcg5 and Abcg8 mRNA expression was remarkably increased in the pravastatin group in comparison with the control group (184%, 264% and 247% of control value, respectively). In the bezafibrate group the hepatic gene expression of Mdr2 was increased (157% of control value), but there were no significant changes in hepatic Abcg5 and Abcg8 mRNA expression compared with the control group. CONCLUSIONS:Compared with Mdr2, Abcg5 and Abcg8 seem to be more essential transporters for biliary secretion of cholesterol. Pravastatin upregulated Abcg5/Abcg8 while bezafibrate did not, which appears to explain the different effects of these compounds on biliary lipid secretion.

journal_name

J Gastroenterol Hepatol

journal_title

Journal of gastroenterology and hepatology

authors

Kamisako T,Ogawa H

doi

10.1111/j.1440-1746.2004.03377.x

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

879-83

issue

eissn

0815-9319

issn

1440-1746

pii

JGH3377

journal_volume

pub_type

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Effects of pravastatin and bezafibrate on biliary lipid excretion and hepatic expression of Abcg5 and Abcg8 in the rat.