Influence of probucol on early experimental atherogenesis in hypercholesterolemic rats.
A possible cellular action for probucol in early atherogenesis was investigated. In diet-induced hypercholesterolemic rats, probucol reduced aortic accumulation of cholesterol without ameliorating monocyte attachment to the arterial endothelium. Under the imposed conditions, circulating cholesterol levels were not significantly altered by probucol. 125I-labeled acetyl LDL uptake and degradation studies with mouse peritoneal macrophages revealed that probucol had an inhibitory effect on the scavenger receptor pathway. The data suggested that the observed beneficial effects of probucol were not related to an early cholesterol-induced injury phase which might involve calcium. Instead, probucol probably through its free radical scavenging property, intervened at a subsequent cellular level to restrict lipid accumulation.
Biochemistry Department, University of Tasmania, Australia.
R
R
Shankar
J D
JD
Sallis
H
H
Stanton
R
R
Thomson
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D006937:Hypercholesterolemia / Q000150:complications*; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000166:cytology*; D010636:Phenols / Q000494:pharmacology*; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008077:Lipoproteins, LDL; D010636:Phenols; D002784:Cholesterol; D011341:Probucol