In Vitro Inhibitory Effects of the Optical Isomers and Metabolites of Fluvastatin on Copper Ion-Induced LDL Oxidation

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概要

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• Fluvastatin is a synthetic hypolipidemic drug which inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. We compared in vitro the antioxidative effects of two enantiomers (3R, 5S and 3S, 5R) of fluvastatin, which is clinically used as a racemic mixture, on copper ion-induced oxidation of human low-density lipoprotein (LDL). Although 3R, 5S-enantiomer of fluvastatin has 30-fold stronger inhibitory activity on HMG-CoA reductase than its optical counterpart, the antioxidative effects of these enantiomers on copper ion-induced LDL oxidation were similar. The antioxidative effects of the metabolites of fluvastatin (M2,M3,M4 and M7) on the copper ion-induced LDL oxidation were also investigated. All the metabolites tested showed an inhbitory effect on this system. Among them, the effects of M2 and M3,which have a phenolic hydroxyl group in each indole moiety, were strong and their potencies were 30-50 times greater than that of fluvastatin. We couclude that not only 3R, 5S-enantiomer of fluvastatin but also its optical counterpart and the metabolites also have a potential to show the anti-atherosclerotic effect through their antioxidative activities on lipid peroxidation.

• 公益社団法人日本薬学会の論文
• 1999-09-15

著者

• 斎藤 徹

  Faculty Of Pharmaceutical Sciences Kanazawa University

• Tanaka K

  Department Of Molecular Engineering Graduate School Of Engineering Kyoto University

• Suzuki T

  Drug Discovery Research Laboratory Sanwa Kagaku Kenkyusho Co. Ltd.

• Narita H

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Tanaka Ken-ichiro

  Faculty Of Pharmaceutical Sciences Okayama University

• 鈴木 徳治

  千葉大 薬

• Suzuki T

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

• Saito T

  Research And Development Headquarters Hokurikit Seiyaku Co. Ltd.

• Saito Takako

  Research And Development Laboratories Maruho Co. Ltd.

• ODAWARA Akio

  Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd.

• Suzuki Toshikazu

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Tanaka Katsuyuki

  Dept. Biol. Sci. Fac. Sci. Hiroshima Univ.

• Narita Hiroshi

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Narita Hiroshi

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd

• TANAKA Keiko

  Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd.

• YASUHARA Mikiko

  Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd.

• SUZUMURA Kuniharu

  Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd.

• Odawara A

  Tanabe Seiyaku Co. Ltd. Saitama Jpn

• Odawara Akio

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Tanaka K

  Dept. Biol. Sci. Fac. Sci. Hiroshima Univ.

• Suzuki T

  Research Unit Of Pharmaceutics College Of Pharmacy Nihon University

• Sugihara T

  Faculty Of Pharmaceutical Sciences Tokushima Bunri University

• Saito T

  Research And Development Laboratories Maruho Co. Ltd.

• Yasuhara M

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Suzumura Kuniharu

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Suzumura Kuniharu

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd

• Narita Hiroshi

  Discovery Research Laboratories Tanabe Seiyaku Co. Ltd.

• Suzumura Kuniharu

  Faculty Of Pharmaceutical Sciences Chiba University

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