Probucol treatment attenuates the aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits.
We examined the effect of probucol on the aortic atherosclerosis already developed in Watanabe heritable hyperlipidemic (WHHL) rabbits at the initiation of treatment. In WHHL rabbits treated with probucol for 5 months from 8 months old, the lesion area in the aorta was significantly (P < 0.05) reduced when compared with that in untreated animals as well as animals at age 8 months. In contrast, plasma cholesterol levels in the probucol-treated group and untreated group during the experiment were not significantly different. LDL prepared from rabbits receiving probucol for 5 months showed resistance to oxidation by copper ions. Plasma CETP activity was significantly (P < 0.05) increased by probucol treatment. An immunohistochemical study showed that macrophages were abundant in the atherosclerotic lesions of untreated rabbits whereas smooth muscle cells were predominant in lesions of probucol-treated rabbits. These results suggest that the atherosclerotic lesion in WHHL rabbits can regress when treated by probucol and that the attenuation of atherosclerosis in this animal involves effects of probucol other than a decrease in plasma cholesterol, for example anti-oxidant activity.
Oshima
R
R
Exploratory Research Laboratories II, Daiichi Pharmaceutical, Tokyo, Japan.
Ikeda
T
T
Watanabe
K
K
Itakura
H
H
Sugiyama
N
N
D000199:Actins / Q000032:analysis / Q000187:drug effects; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology; D001013:Aorta, Thoracic / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D001018:Aortic Diseases / Q000188:drug therapy; D001161:Arteriosclerosis / Q000150:complications / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000097:blood / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake / Q000187:drug effects; D006023:Glycoproteins; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D009130:Muscle, Smooth / Q000737:chemistry / Q000187:drug effects; D010084:Oxidation-Reduction; D011341:Probucol / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011817:Rabbits; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D017539:Tunica Intima / Q000737:chemistry / Q000166:cytology / Q000187:drug effects
D000199:Actins; D000924:Anticholesteremic Agents; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D006023:Glycoproteins; D002784:Cholesterol; D011341:Probucol