title: Probucol and atherosclerosis in the Watanabe heritable hyperlipidemic rabbit--long-term antiatherogenic effect and effects on established plaques.
abstract: We performed two studies to investigate the effect of probucol on atherogenesis in vivo in the Watanabe heritable hyperlipidemic (WHHL) rabbit. In the first study (Study A), probucol was administered to 2-month-old WHHL rabbits, to evaluate its long-term effect. When killed at about 1.5 years of age, the percentage area of aorta covered with atherosclerotic plaque in probucol-treated rabbits was markedly less than that seen in non-treated rabbits (23.0 +/- 11.4% vs. 87.7 +/- 8.1%, M +/- S.D., P less than 0.001). In the second study (study B), administration of probucol was commenced with 8-month-old WHHL rabbits to investigate whether the drug was effective for limiting atherosclerosis in rabbits in which plaques had already developed. When killed after 6 months of treatment, the percentage area of aorta covered with plaque was 38.1 +/- 12.1% in treated rabbits and 82.7 +/- 22.6% in non-treated rabbits (P less than 0.02). Microscopic observations of lesions also supported the effect of probucol. Probucol treatment resulted in a change not only in the size but also the composition of lesions. Thus, probucol was effective in preventing atherosclerosis in long-term studies at both early and late stages.
authors.affiliation: Department of Geriatric Medicine, Faculty of Medicine, Kyoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagano
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: M
authors.initials: M
authors.lastname: Cho
authors.forename: Y
authors.initials: Y
authors.lastname: Ueda
authors.forename: T
authors.initials: T
authors.lastname: Kita
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D011341:Probucol / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors
chemical_list: D008055:Lipids; D002784:Cholesterol; D011341:Probucol