Effects of bezafibrate on hepatic cholesterol metabolism
The influence of bezafibrate treatment on hepatic cholesterol metabolism was studied in rats and in humans. The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cho...
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| Veröffentlicht in: | European journal of clinical pharmacology 1991, Vol.40 (1), p.S33-S36 |
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| container_title | European journal of clinical pharmacology |
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| creator | STAHLBERG, D REIHNER, E EWERTH, S EINARSSON, K ANGELIN, B |
| description | The influence of bezafibrate treatment on hepatic cholesterol metabolism was studied in rats and in humans. The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cholesterol acyltransferase (ACAT)] were suppressed by bezafibrate treatment in rats, but only the ACAT activity was significantly decreased when the activity was related to total liver weight. In humans, HMG-CoA reductase activity was increased about twice in the treated normolipidemic gallstone patients. In contrast, the concentration of lathosterol in serum decreased, indicating depression of the cholesterol synthesis. The increase in HMG-CoA reductase activity may be a compensatory effect of an inhibition of some other enzymes in the synthesis of cholesterol, as in vitro study on liver microsomes excluded a direct inhibitory effect of bezafibrate on HMG-CoA reductase. The ACAT activity was not significantly changed, and the cholesterol 7 alpha-hydroxylase activity was decreased by 55-60% compared with controls. The LDL-receptor-binding activity was unaffected by bezafibrate treatment. |
| doi_str_mv | 10.1007/bf01409405 |
| format | Article |
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The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cholesterol acyltransferase (ACAT)] were suppressed by bezafibrate treatment in rats, but only the ACAT activity was significantly decreased when the activity was related to total liver weight. In humans, HMG-CoA reductase activity was increased about twice in the treated normolipidemic gallstone patients. In contrast, the concentration of lathosterol in serum decreased, indicating depression of the cholesterol synthesis. The increase in HMG-CoA reductase activity may be a compensatory effect of an inhibition of some other enzymes in the synthesis of cholesterol, as in vitro study on liver microsomes excluded a direct inhibitory effect of bezafibrate on HMG-CoA reductase. The ACAT activity was not significantly changed, and the cholesterol 7 alpha-hydroxylase activity was decreased by 55-60% compared with controls. The LDL-receptor-binding activity was unaffected by bezafibrate treatment.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/bf01409405</identifier><identifier>PMID: 2044640</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Animals ; Bezafibrate - pharmacology ; Bile - metabolism ; Biological and medical sciences ; Cholesterol - metabolism ; General and cellular metabolism. Vitamins ; Humans ; Lipid Metabolism ; Liver - drug effects ; Liver - metabolism ; Medical sciences ; Pharmacology. 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The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cholesterol acyltransferase (ACAT)] were suppressed by bezafibrate treatment in rats, but only the ACAT activity was significantly decreased when the activity was related to total liver weight. In humans, HMG-CoA reductase activity was increased about twice in the treated normolipidemic gallstone patients. In contrast, the concentration of lathosterol in serum decreased, indicating depression of the cholesterol synthesis. The increase in HMG-CoA reductase activity may be a compensatory effect of an inhibition of some other enzymes in the synthesis of cholesterol, as in vitro study on liver microsomes excluded a direct inhibitory effect of bezafibrate on HMG-CoA reductase. The ACAT activity was not significantly changed, and the cholesterol 7 alpha-hydroxylase activity was decreased by 55-60% compared with controls. The LDL-receptor-binding activity was unaffected by bezafibrate treatment.</description><subject>Animals</subject><subject>Bezafibrate - pharmacology</subject><subject>Bile - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cholesterol - metabolism</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Humans</subject><subject>Lipid Metabolism</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Medical sciences</subject><subject>Pharmacology. 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Vitamins</topic><topic>Humans</topic><topic>Lipid Metabolism</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>STAHLBERG, D</creatorcontrib><creatorcontrib>REIHNER, E</creatorcontrib><creatorcontrib>EWERTH, S</creatorcontrib><creatorcontrib>EINARSSON, K</creatorcontrib><creatorcontrib>ANGELIN, B</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>STAHLBERG, D</au><au>REIHNER, E</au><au>EWERTH, S</au><au>EINARSSON, K</au><au>ANGELIN, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of bezafibrate on hepatic cholesterol metabolism</atitle><jtitle>European journal of clinical pharmacology</jtitle><addtitle>Eur J Clin Pharmacol</addtitle><date>1991</date><risdate>1991</risdate><volume>40</volume><issue>1</issue><spage>S33</spage><epage>S36</epage><pages>S33-S36</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>The influence of bezafibrate treatment on hepatic cholesterol metabolism was studied in rats and in humans. The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cholesterol acyltransferase (ACAT)] were suppressed by bezafibrate treatment in rats, but only the ACAT activity was significantly decreased when the activity was related to total liver weight. In humans, HMG-CoA reductase activity was increased about twice in the treated normolipidemic gallstone patients. In contrast, the concentration of lathosterol in serum decreased, indicating depression of the cholesterol synthesis. The increase in HMG-CoA reductase activity may be a compensatory effect of an inhibition of some other enzymes in the synthesis of cholesterol, as in vitro study on liver microsomes excluded a direct inhibitory effect of bezafibrate on HMG-CoA reductase. The ACAT activity was not significantly changed, and the cholesterol 7 alpha-hydroxylase activity was decreased by 55-60% compared with controls. The LDL-receptor-binding activity was unaffected by bezafibrate treatment.</abstract><cop>Heidelberg</cop><cop>Berlin</cop><pub>Springer</pub><pmid>2044640</pmid><doi>10.1007/bf01409405</doi></addata></record> |
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| ispartof | European journal of clinical pharmacology, 1991, Vol.40 (1), p.S33-S36 |
| issn | 0031-6970 1432-1041 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Bezafibrate - pharmacology Bile - metabolism Biological and medical sciences Cholesterol - metabolism General and cellular metabolism. Vitamins Humans Lipid Metabolism Liver - drug effects Liver - metabolism Medical sciences Pharmacology. Drug treatments |
| title | Effects of bezafibrate on hepatic cholesterol metabolism |
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