Suppressive effects of cacao liquor polyphenols (CLP) on LDL oxidation and the development of atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic rabbits.
We investigated the properties of cacao liquor polyphenols (CLP), which have an antioxidative effect on low-density lipoprotein (LDL) and an anti-atherosclerotic effect in the spontaneous familial hypercholesterolemic model, the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit. After 6 months of dietary administration of CLP at 1% (w/w) to the KHC rabbits, a higher total cholesterol concentration was observed in the treatment group compared to the control group. However, no other effects were noted in lipid profiles in plasma or lipoproteins. The plasma concentration of thiobarbituric acid reactive substances (TBARS), which is a lipid-peroxidation index, was significantly decreased 1 month after the start of CLP administration compared to that of the control group. The antioxidative effect of CLP on LDL was observed from 2 to 4 months of administration. The area of atherosclerotic lesions in the aorta in the CLP group (32.01+/-1.58%) was significantly smaller than that in the control group (47.05+/-3.29%), and the tissue cholesterol and TBARS concentrations were lower in the CLP group than in the control group. The anti-atherosclerotic effect of CLP was confirmed both rheologically and histopathologically. An in vitro study using KHC rabbit-derived LDL revealed that CLP significantly prolonged the lag time of LDL oxidation that was induced by a lipophilic azo-radical initiator, 2,2'-azobis(4-methoxy)-2,4-dimethylvaleronitrile (V-70), or Cu(2+) from a low concentration of 0.1 microg/mL. The antioxidative effect of CLP was superior to those of the well-known antioxidative substances, vitamin C, vitamin E and probucol. Therefore, CLP suppressed the generation of atherosclerosis, and its antioxidative effect appeared to have an important role in its anti-atherosclerotic activity.
Kurosawa
Tohru
T
Toxicology Laboratory, Pharmaceutical Development Department, Meiji Seika Kaisha Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. toru_kurosawa@meiji.co.jp
Itoh
Fumi
F
Nozaki
Aiko
A
Nakano
Yoshihisa
Y
Katsuda
Shin-ichiro
S
Osakabe
Naomi
N
Tsubone
Hirokazu
H
Kondo
Kazuo
K
Itakura
Hiroshige
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000503:physiopathology*; D002099:Cacao / Q000737:chemistry*; D008078:Cholesterol, LDL / Q000737:chemistry* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000150:complications*; D008297:Male; D010084:Oxidation-Reduction; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols; D011817:Rabbits
D000975:Antioxidants; D008078:Cholesterol, LDL; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols