Antiatherogenic effects of the antioxidant BO-653 in three different animal models.
Antioxidants have been proposed to have antiatherogenic potential by their inhibition of low density lipoprotein (LDL) oxidation. Here, we report an antioxidant, BO-653 (2,3-dihydro-5-hydroxy-2, 2-dipentyl-4,6-di-tert-butylbenzofuran), designed to exhibit antioxidative potency comparable to that of alpha-tocopherol, but yet possess a high degree of lipophilicity comparable to that of probucol. BO-653 exhibits a high affinity for LDL and is well distributed in aortic vessels in vivo. In atherosclerosis models of rabbits and mice, BO-653 has been shown to be able to suppress the formation of atherosclerotic lesions without untoward side effects. Specifically, there was no reduction of high density lipoprotein levels. This antioxidant provides additional evidence in support of the oxidized-LDL hypothesis, and itself is a promising candidate antioxidant for clinical use.
Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan.
O
O
Cynshi
Y
Y
Kawabe
T
T
Suzuki
Y
Y
Takashima
H
H
Kaise
M
M
Nakamura
Y
Y
Ohba
Y
Y
Kato
K
K
Tamura
A
A
Hayasaka
A
A
Higashida
H
H
Sakaguchi
M
M
Takeya
K
K
Takahashi
K
K
Inoue
N
N
Noguchi
E
E
Niki
T
T
Kodama
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001572:Benzofurans / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D011817:Rabbits; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D000975:Antioxidants; D001572:Benzofurans; D004041:Dietary Fats; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL