EFFECT OF HYPOLIPIDEMIC DRUGS ON KEY ENZYME-ACTIVITIES RELATED TO LIPID-METABOLISM IN NORMOLIPIDEMIC RABBITS

The effect of atorvastatin (3 mg kg(-1) day(-1)), simvastatin (3 mg kg (-1) day(-1)) and bezafibrate (100 mg kg(-1) day(-1)) administered for 4 weeks to male New Zealand white rabbits on enzyme activities relate d to lipid metabolism has been studied. Only the statins reduced plasm a cholesterol values, while none of the drugs modified plasma triglyce ride or high density lipoprotein (HDL)-cholesterol concentrations, nor the activity of enzymes such as hepatic diacylglycerol acyltransferas e, Lipoprotein lipase or hepatic lipase, directly involved in triglyce ride metabolism. Both statins elicited similar increases in the hepati c microsomal 3-hydroxy-3-methyl-glutaryl Coenzyme A (CoA) reductase ac tivity (147 and 109% induction for simvastatin and atorvastatin, respe ctively), and none of the drugs assayed modified hepatic acyl-coenzyme A:cholesterol acyltransferase activity significantly. Only bezafibrat e induced a significant 57% reduction in the activity of hepatic micro somal cholesterol 7 alpha-hydroxylase. Regarding the rate limiting enz yme of phosphatidylcholine biosynthesis, CTP:phosphocholine cytidylyl transferase, atorvastatin and bezafibrate behaved similarly, decreasin g the enzyme activity in the liver by 45% and 54%, respectively; simva statin induced no modification of this activity. The reduction of CTP: phosphocholine cytidylyl transferase activity is not caused by a direc t inhibition of the enzyme by bezafibrate and atorvastatin. Further, t he inhibitory effect of atorvastatin appears to be unrelated to the in hibition of 3-hydroxy-3-methyl-glutaryl CoA reductase elicited in vivo . (C) 1998 Elsevier Science B.V.