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Different effect of simvastatin and atorvastatin on key enzymes involved in VLDL synthesis and catabolism in high fat/cholesterol fed rabbits
Author(s) -
Verd Joan C,
Peris Cristina,
Alegret Marta,
Díaz Cristina,
Hernández Gonzalo,
Vázquez Manuel,
Adzet Tomás,
Laguna Juan C,
Sánchez Rosa M
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702668
Subject(s) - simvastatin , atorvastatin , endocrinology , medicine , sterol o acyltransferase , triglyceride , chemistry , cholesterol , very low density lipoprotein , cholesteryl ester , reductase , lipoprotein lipase , hmg coa reductase , lovastatin , lipoprotein , biochemistry , biology , enzyme
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