Atherosclerotic lesion development in hypercholesterolemic Japanese quail following probucol treatment: a biochemical and morphologic evaluation.
Probucol, a cholesterol-lowering agent which possesses antioxidant properties, was evaluated in hypercholesterolemic Japanese quail in order to assess the significance of antioxidant therapy on the development of atherosclerosis. Forty quail were fed a 0.5% cholesterol diet containing 0, 100, 200 or 500 mg kg-1 probucol for 2 months. At necropsy, plasma total and lipoprotein cholesterol and lipoprotein distribution were unchanged despite plasma probucol levels of 50 to 59 micrograms ml-1. The cholesteryl ester content of the liver and blood vasculature (brachiocephalic artery and aortic arch combined) was reduced by 33% and 62%, respectively, in animals given 500 mg kg-1 probucol. The vascular free cholesterol content was also reduced by 43 to 60% over the probucol dose range. Morphometric analysis of the brachiocephalic artery revealed that probucol reduced the incidence of lesions containing esterase-positive cells from 62% in untreated animals to 26% and 13% in animals administered 200 and 500 mg kg-1 probucol, respectively. No difference in mean wall thickness or area of the bracheocephalic artery was noted between the groups. Thus, we conclude that probucol can blunt the cholesteryl ester and macrophage enrichment of atherosclerotic lesions and this activity appears to be mediated by the compound's antioxidant properties since the changes noted were seen in the absence of alterations in plasma total and lipoprotein cholesterol levels.
Bocan
T M
TM
Department of Atherosclerosis Research, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48105.
Mazur
M J
MJ
Mueller
S B
SB
Charlton
G
G
Kieft
K A
KA
Krause
B R
BR
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003370:Coturnix / Q000378:metabolism*; D004036:Diet, Atherogenic; D006651:Histocytochemistry; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D011341:Probucol / Q000097:blood / Q000627:therapeutic use*
D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D008074:Lipoproteins; D002784:Cholesterol; D011341:Probucol