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 α...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-08, Vol.95 (17), p.10123-10128
Main Authors: Cynshi, Osamu, Kawabe, Yoshiki, Suzuki, Tsukasa, Takashima, Yoshiaki, Kaise, Hiroshi, Nakamura, Minako, Ohba, Yasuhiro, Kato, Yoshiaki, Tamura, Kunio, Hayasaka, Akira, Higashida, Atsuko, Sakaguchi, Hisashi, Takeya, Motohiro, Takahashi, Kiyoshi, Inoue, Kenji, Noguchi, Noriko, Niki, Etsuo, Kodama, Tatsuhiko
Format: Article
Language:English
Subjects:
Animal models
Animals
Antioxidants
Antioxidants - pharmacology
Arteriosclerosis - metabolism
Arteriosclerosis - pathology
Arteriosclerosis - prevention & control
Atherosclerosis
Benzofurans - pharmacology
Biological Sciences
Chemiluminescence
Cholesterols
Dietary Fats - administration & dosage
Disease Models, Animal
Drug Evaluation, Preclinical
Female
HDL lipoproteins
In Vitro Techniques
Lesions
Lipids
Lipoproteins
Lipoproteins, HDL - blood
Lipoproteins, LDL - blood
Male
Medical research
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Knockout
Oxidation
Oxidation-Reduction
Rabbits
Receptors, LDL - genetics
Receptors, LDL - metabolism
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Summary: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 α -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 lesion 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.17.10123