Antiatherosclerotic effects of antioxidants are lesion-specific when evaluated in hypercholesterolemic New Zealand white rabbits.
Oxidative modification of LDL may represent an initiating event in the formation of monocyte-macrophage foam cells, a major cell present in fatty streaks and atherosclerotic fibrous plaques. Therefore, we studied the effect of such antioxidants as probucol (500 mg/kg) and vitamins E and C (500 mg/kg each) on the regression of induced iliac-femoral lesions and progression of naturally occurring thoracic aortic fatty streak lesions in hypercholesterolemic New Zealand White rabbits. Following an initial 9-week lesion induction phase, both therapies were evaluated for 8 weeks. Probucol lowered plasma cholesterol 47% while vitamins E and C had no effect on plasma cholesterol. Probucol decreased the cholesteryl ester (CE) content of the thoracic aorta by 31% without changing the thoracic aortic lesion coverage. Vitamins E and C decreased thoracic aortic CE content by 40% and lesion coverage by 46%. Neither probucol nor vitamins E and C altered the CE content, lesion size, or macrophage/lesion ratio of the iliac-femoral artery. Thus, we conclude that the effects of antioxidants are specific to the stage of atherosclerotic lesion development. Antioxidant therapy alters the progression and cholesteryl ester enrichment of diet-induced thoracic aortic fatty streaks but has no effect on the progression and/or regression of more complicated injury-induced iliac-femoral lesions.
Bocan
T M
TM
Department of Pharmacology, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Mueller
S B
SB
Brown
E Q
EQ
Uhlendorf
P D
PD
Mazur
M J
MJ
Newton
R S
RS
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001011:Aorta / Q000737:chemistry / Q000473:pathology; D001161:Arteriosclerosis / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D001205:Ascorbic Acid / Q000627:therapeutic use; D001808:Blood Vessels / Q000737:chemistry / Q000473:pathology; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D002788:Cholesterol Esters / Q000032:analysis / Q000097:blood; D005263:Femoral Artery / Q000737:chemistry / Q000473:pathology; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications*; D008055:Lipids / Q000032:analysis / Q000097:blood; D008074:Lipoproteins / Q000032:analysis / Q000097:blood; D008297:Male; D011341:Probucol / Q000627:therapeutic use; D011817:Rabbits; D014810:Vitamin E / Q000627:therapeutic use
D000975:Antioxidants; D002788:Cholesterol Esters; D008055:Lipids; D008074:Lipoproteins; D014810:Vitamin E; D002784:Cholesterol; D011341:Probucol; D001205:Ascorbic Acid