Antiatherogenic effects of the antioxidant BO-653 in three different animal models

  • Osamu Cynshi
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Yoshiki Kawabe
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Tsukasa Suzuki
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Yoshiaki Takashima
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Hiroshi Kaise
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Minako Nakamura
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Yasuhiro Ohba
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Yoshiaki Kato
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Kunio Tamura
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Akira Hayasaka
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Atsuko Higashida
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Hisashi Sakaguchi
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Motohiro Takeya
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Kiyoshi Takahashi
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Kenji Inoue
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Noriko Noguchi
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Etsuo Niki
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan
  • Tatsuhiko Kodama
    Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba-shi, Shizuoka 412, Japan; The Second Department of Biochemistry, Kumamoto University Medical School, 2-2-1 Honjo, Kumamoto 860, Japan; Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113, Japan; and Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153, Japan

抄録

<jats:p> 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- <jats:italic>tert-</jats:italic> 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 <jats:italic>in vivo</jats:italic> . 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. </jats:p>

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