Effect of probucol on blood cholesterol and basal and lovastatin-induced 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in mice.
The drug probucol is known to reduce levels of blood cholesterol and to have antioxidant effects on lipoproteins that may alter their metabolism. While studying probucol feeding in mice, we observed that the drug lowered total hepatic, but not gut, 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase activities during the diurnal cycle. Hepatic fatty acyl:cholesterol acyl transferase activity and cholesterol content were not measurably affected by probucol. Probucol also abolished the induction of HMG CoA reductase activity that resulted from feeding of lovastatin, when activity was measured in microsomes washed free of drugs. These effects are consistent with previous reports that probucol increases fractional clearance of lipoprotein cholesterol by the liver. The findings raise the possibility that some patients with hypercholesterolemia may benefit from combined therapy with lovastatin plus probucol.
Gebhard
R L
RL
Department of Medicine, Veterans Administration Medical Center, Minneapolis, MN 55417.
Prigge
W F
WF
Andreini
J P
JP
Freeman
M L
ML
D000818:Animals; D002784:Cholesterol / Q000097:blood*; D004790:Enzyme Induction; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis*; D007413:Intestinal Mucosa / Q000201:enzymology; D008148:Lovastatin / Q000494:pharmacology*; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D011341:Probucol / Q000494:pharmacology*; D011973:Receptors, LDL / Q000187:drug effects; D002785:Sterol O-Acyltransferase / Q000032:analysis
D011973:Receptors, LDL; D002784:Cholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D002785:Sterol O-Acyltransferase; D011341:Probucol