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 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, acylcoenzyme 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.
Verd
J C
JC
Unidad de Farmacología y Farmacognosia, Dept. Farmacología y Química Terapéutica, Facultad de Farmacia, Núcleo Universitario de Pedralbes, Barcelona, Spain.
Peris
C
C
Alegret
M
M
Díaz
C
C
Hernández
G
G
Vázquez
M
M
Adzet
T
T
Laguna
J C
JC
Sánchez
R M
RM
D000214:Acyl Coenzyme A / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D019916:Choline-Phosphate Cytidylyltransferase / Q000187:drug effects / Q000378:metabolism; D004798:Enzymes / Q000187:drug effects* / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000187:drug effects / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology*; D002785:Sterol O-Acyltransferase / Q000187:drug effects / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D000214:Acyl Coenzyme A; D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D004798:Enzymes; D006538:Heptanoic Acids; D008055:Lipids; D008079:Lipoproteins, VLDL; D010743:Phospholipids; D011758:Pyrroles; D014280:Triglycerides; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D000069059:Atorvastatin; D019821:Simvastatin; D002785:Sterol O-Acyltransferase; D019916:Choline-Phosphate Cytidylyltransferase; D008071:Lipoprotein Lipase