Different effect of simvastatin and atorvastatin on key enzymes involved in VLDL synthesis and catabolism in high fat/cholesterol fed rabbits

The effects of atorvastatin (3 mg kg−1) and simvastatin (3 mg kg−1) on hepatic enzyme activities involved in very low density lipoprotein metabolism were studied in coconut oil/cholesterol fed rabbits. Plasma cholesterol and triglyceride levels increased 19 and 4 fold, respectively, after 7 weeks of...

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Bibliographic Details
Published in:British journal of pharmacology 1999-07, Vol.127 (6), p.1479-1485
Main Authors: Verd, Joan C, Peris, Cristina, Alegret, Marta, Díaz, Cristina, Hernández, Gonzalo, Vázquez, Manuel, Adzet, Tomás, Laguna, Juan C, Sánchez, Rosa M
Format: Article
Language:English
Subjects:
Acyl Coenzyme A - drug effects
Acyl Coenzyme A - metabolism
Animals
Anticholesteremic Agents - pharmacology
Atorvastatin
Atorvastatin Calcium
Biological and medical sciences
Cholesterol, Dietary - pharmacology
Choline-Phosphate Cytidylyltransferase - drug effects
Choline-Phosphate Cytidylyltransferase - metabolism
CTP:phosphocholine cytidylyl transferase
Enzymes - drug effects
Enzymes - metabolism
General and cellular metabolism. Vitamins
Heptanoic Acids - pharmacology
high fat/cholesterol fed rabbits
Lipids - blood
lipoprotein lipase
Lipoprotein Lipase - drug effects
Lipoprotein Lipase - metabolism
Lipoproteins, VLDL - drug effects
Lipoproteins, VLDL - metabolism
Liver - drug effects
Liver - metabolism
Male
Medical sciences
Pharmacology. Drug treatments
Phospholipids - metabolism
Pyrroles - pharmacology
Rabbits
simvastatin
Simvastatin - pharmacology
Sterol O-Acyltransferase - drug effects
Sterol O-Acyltransferase - metabolism
Triglycerides - metabolism
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Summary:The effects of atorvastatin (3 mg kg−1) and simvastatin (3 mg kg−1) on hepatic enzyme activities involved in very low density lipoprotein metabolism were studied in coconut oil/cholesterol fed rabbits. Plasma cholesterol and triglyceride levels increased 19 and 4 fold, respectively, after 7 weeks of feeding. Treatment with statins during the last 4 weeks of feeding abolished the progression of hypercholesterolaemia and reduced plasma triglyceride levels. 3‐Hydroxy‐3‐methyl‐glutaryl Coenzyme A reductase, acyl‐coenzyme A:cholesterol acyltransferase, phosphatidate phosphohydrolase and diacylglycerol acyltransferase activities were not affected by drug treatment. Accordingly, hepatic free cholesterol, cholesteryl ester and triglyceride content were not modified. Simvastatin treatment caused an increase (72%) in lipoprotein lipase activity without affecting hepatic lipase activity. Atorvastatin caused a reduction in hepatic phospholipid content and a compensatory increase in CTP:phosphocholine cytidylyl transferase activity. The results presented in this study suggest that, besides the inhibitory effect on 3‐hydroxy‐3‐methyl‐glutaryl Coenzyme A reductase, simvastatin and atorvastatin may have additional effects that contribute to their triglyceride‐lowering ability. British Journal of Pharmacology (1999) 127, 1479–1485; doi:10.1038/sj.bjp.0702668
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0702668