[Prevention of atherosclerosis using an antioxidant].
The question of whether probucol is able to prevent the progression of atheromatous formation in the aorta of homozygous WHHL rabbits, an animal model for familial hypercholesterolemia, was investigated in vivo. Most foam cells in early stages of atherosclerotic lesions have been proved to be derived from monocyte originated macrophages. Epidemiological studies have shown that elevated LDL is one of the major risk factors for atherosclerosis. Native LDL, however, does not transform macrophages into foam cells in vitro. Recently oxidized LDL has been suggested to play an important role in atherogenesis by facilitating the accumulation of lipids in macrophages in vitro. Probucol, originally developed as an antioxidant, prevents this oxidative modification of LDL in vitro. Moreover, there are some clinical reports that probucol causes a regression of cutaneous and tendon xanthomas in homozygous FH patients. We have performed three studies to investigate the effects of probucol on aortic atherosclerosis in WHHL rabbits. In the study 1, WHHL rabbits aged 2 months were fed 1 g/day of probucol and killed 6 months later. Aortic atherosclerosis developed in the control group of rabbits. However, probucol-treated rabbits showed few lesions. The percentage of the surface area of the total thoracic aorta with visible plaque in control vs. treated group was 54.2% vs. 7.0%, respectively. In study 2, we investigated the long term effect of probucol on WHHL rabbits. The administration was started at 2 months and was continued for 16 months. The degree of lesions was significantly suppressed in rabbits of probucol treatment group, although the aortic lesions progressed in both groups of rabbits compared with the result of study 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishii
K
K
Department of Geriatric Medicine, Faculty of Medicine, Kyoto University.
Kita
T
T
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001018:Aortic Diseases / Q000378:metabolism / Q000517:prevention & control; D001161:Arteriosclerosis / Q000378:metabolism / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010636:Phenols / Q000627:therapeutic use*; D011341:Probucol / Q000627:therapeutic use*; D011817:Rabbits
D000975:Antioxidants; D008078:Cholesterol, LDL; D010636:Phenols; D011341:Probucol