Antioxidant effects of 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran and alpha-tocopherol in hyperlipidemic mice as evaluated by hydroxyoctadecadienoic acid and 7-hydroxycholesterol.
It has been hypothesized that oxidative modification of low density lipoprotein plays a key role in the pathogenesis of atherosclerosis. In order to elucidate the role of lipid oxidation and its inhibition in vivo, apolipoprotein E and alpha-tocopherol (alphaT) transfer protein double knockout (ApoE(-/-)alpha-TTP(-/-)) and apolipoprotein E knockout (ApoE(-/-)) mice fed with a vitamin E-depleted diet and a diet containing 0.002 wt.% alphaT, respectively, were used with or without the treatment of a synthetic antioxidant 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran (BO-653, 0.2 wt.%). The lipid oxidation markers of total hydroxylinoleic acid (tHODE), 8-iso-prostaglandin F(2alpha), and 7-hydroxycholesterol (t7-OHCh) in the blood, liver, and brain were inclusively measured with or without an excessive cholesterol-feeding (Ch-diet). The tHODE levels were elevated by Ch-diet in the plasma and brain of ApoE(-/-)alpha-TTP(-/-) mice and in the liver of ApoE(-/-) mice without BO-653. The levels of t7-OHCh in the liver were also increased due to the Ch-diet, and the ratio of t7-OHCh to the parent compound cholesterol was reduced to the control levels by BO-653. In summary, it was demonstrated by biomarkers, tHODE and t7-OHCh, that the added BO-653 in their diets exerted antioxidative effects in vivo under the condition of reduced vitamin E.
Yoshida
Yasukazu
Y
Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan. yoshida-ya@aist.go.jp
Hayakawa
Mieko
M
Itoh
Nanako
N
Habuchi
Yoko
Y
Inoue
Ruriko
R
Chen
Zhi-Hua
ZH
Cao
Jiaofei
J
Cynshi
Osamu
O
Jishage
Kou-Ichi
K
Niki
Etsuo
E
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001572:Benzofurans / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000378:metabolism*; D006888:Hydroxycholesterols / Q000378:metabolism*; D006949:Hyperlipidemias; D000960:Hypolipidemic Agents / Q000494:pharmacology; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024502:alpha-Tocopherol / Q000494:pharmacology*
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D001057:Apolipoproteins E; D001572:Benzofurans; D002352:Carrier Proteins; D005231:Fatty Acids, Unsaturated; D006888:Hydroxycholesterols; D000960:Hypolipidemic Agents; C017763:alpha-tocopherol transfer protein; C495366:hydroxyoctadecadienoic acid; D024502:alpha-Tocopherol