Fluvastatin, an HMG-CoA Reductase Inhibitor, Protects LDL from Oxidative Modification in Hypercholesterolemic Rabbits

スポンサーリンク

概要

• 論文の詳細を見る

• The antioxidative effect of fluvastatin sodium (fluvastatin) on low-density lipoprotein (LDL) was evaluated in vivo and in vitro. Since ex vivo measurement of the LDL oxidizability is reported to reflect the response of the atherosclerotic process, LDL isolated from rabbits fed a high cholesterol diet for 4 weeks with or without fluvastatin, pravastatin or α-tocopherol administration was oxidized by copper ions to estimate conjugated diene formation. Fluvastatin but not pravastatin significantly prolonged the lag time of LDL oxidized by copper ions ex vivo without affecting plasma cholesterol levels at a dose of 3 mg/kg after four weeks of treatment. α-Tocopherol-treated rabbits showed dramatically elongated LDL oxidation lag time at a dose of 150 mg/kg. In order to assess the mechanism, the content of α-tocopherol, a major endogenous antioxidant in LDL was measured, and we found that only LDL isolated from α-tocopherol-treated rabbits contained a significantly larger amount of α-to-copherol than that from high cholesterol control rabbits. To elucidate the mechanism further, the effect of fluvastatin on conjugated diene formation during copper-induced LDL oxidation in vitro was studied. Fluvastatin not only prolonged lag time, but also suppressed the rate of LDL oxidation, both in a dose dependent manner above 1μM, while pravastatin showed no effect. These results suggest the direct antioxidative effect of fluvastatin on LDL oxidation in vivo. Since oxidation of LDL is an important step in the initiation and progression of atherosclerosis, fluvastatin may reduce the risk of this condition not only by lowering plasma cholesterol but also by protecting LDL from oxidation.

• 公益社団法人日本薬学会の論文
• 2000-05-01

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.

• TAKAHASHI Masakatsu

  Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• AOKI Shoichi

  Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• Aoki Shoichi

  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.

• Takahashi Masakatsu

  Discovery Research Laboratory Tanabe Seiyaku 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

関連論文

• Pharmacological Activity of Chemically Modified Subfragment from Human Serum IgG. XIV. Inhibitory Effect of Carboxamide-Methylated Light Chain (G_1L) on Tyrosine Phosphorylation and Tumor Necrosis Factor-α Production from Murine Macrophages Stimulated by
• Induction of Unresponsiveness of Antigen-Specific T Lymphocytes by Oral Administration of Cedar Pollen Extract in Mice
• Studies on Pharmacological Activation of Human Immunoglobulin G by Chemical Modification and Active Subfragments. XIII. Effect of Carboxamidemethylated Fc Fragment (CM-Fc) on Type II Collagen-Induced Arthritis in DBA/1J Mice
• Abnormal Accumulation of Copper-Metallothionein in the Liver and Kidney of Long-Evans Rats with a Cinnamon-Like Coat Color (LEC Rats)
• Serum Hepatocyte Growth Factor Activity and Hepatocyte Proliferation in Long-Evans with a Cinnamon-Like Coat Color Rats with Hepatic Lesions
• Studies on Thermophile Products. VI. Activation of Mouse Peritoneal Macrophages by Bis(2-hydroxyethyl) Trisulfide
• Studies on Pharmacological Activation of Human Serum Immunoglobulin G by Chemical Modification and Active Subfragments. IX. Anti-inflammatory Activity of Completely Alkylated Heavy Chain (C.Fr.I-H)
• Preparation of Biologically Active and Site Specifically Radioiodinated Recombinant Human Insulin-like Growth Factor-I
• Inhibitory Effects of Bis(2-aminohexyl)disulfide and Its Analogues on Polymorphonuclear Leukocyte Functions in Vitro
• ISOLATION OF A NEW ANTITUMOR SUBSTANCE FROM BACILLUS STEAROTHERMOPHILUS
• Purines. LXIX. Direct N(1)-Oxidation of 7-Benzyladenine and Stepwise Syntheses of Its N(1)- and N(3)-Oxides
• Purines. LXVII. An Alternative Synthesis of Adenine 7-Oxide : N-Oxidation of the Adenine Ring Utilizing Blocking/Deblocking at the 1-Position
• Purines. LXVI. Adenine 7-Oxide : Its Synthesis, Chemical Properties, and X-ray Molecular Structure
• Purines. LII. Synthesis and Biological Evaluation of 8-Methylguanine 7-Oxide and Its 9-Arylmethyl Derivatives
• Purines. LI. Synthesis and Biological Activity of Hypoxanthine 7-N-Oxide and Related Compounds
• Purines. L. Synthesis and Antileukemic Activity of the Antibiotic Guanine 7-Oxide and Its 9-Substituted Derivatives
• 2-(3-Pyridyl)thiazolidine-4-carboxamide Derivatives. II. Structure-Activity Relationships and Active Configuration of 2-(3-Pyridyl)thiazolidine-4-carboxamides as Platelet-Activating Factor Receptor Antagonists
• 2-(3-Pyridyl)thiazolidine-4-carboxamides. 1. Novel Orally Active Antagonists of Platelet-Activating Factor (PAF)
• Purines. LX. Dimroth Rearrangement and Concomitant Hydrolytic Deamination of 7-Alkyl-1-methyladenines
• Involvement of a Cytochrome P4502D Subfamily in Human Liver Microsomal Bunitrolol 4-Hydroxylation
• Synthesis and Biological Activity of the Metabolites of N-[2-(1-Azabicyclo[3.3.0]octan-5-yl)ethyl]-2-nitroaniline Fumarate (SK-946)
• Synthesis of (1-Azabicyclo[3.3.0]octanyl)methyl-Substituted Aromatic Heterocycles and Their Muscarinic Activity
• Synthesis and Thromboxane A_2 Antagonistic Activity of [[1-Aryl(or Benzyl)-1-(benzenesulfonamide)methyl]phenyl]alkanoic Acid Derivatives
• Laxative and Anti-diarrheal Activity of Polycarbophil in Mice and Rats
• An Improved Synthesis of Butyl 4-[(4-Amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (AU-224)
• Synthesis and Gastrointestinal Prokinetic Activity of Novel Benzamide Derivatives with Amphoteric Side Chains
• Calcium Polycarbophil, a Water Absorbing Polymer, Increases Bowel Movement and Prevents Sennoside-Induced Diarrhea in Dogs
• Purines. XLI. : An Alternative Synthesis and the Chemical Behavior of 7,9-Dialkyladeninium Salts
• Purines. XXXVIII. A General Synthesis of 7,9-Dialkyladeninium Salts from 9-Alkyladenines by Regioselective Alkylation : Utilization of an N^6-Alkoxy Group as a Control Synthon
• Purines. XXX. : Ring Fission of 3,7-Dialkyladenines by Alkaline Hydrolysis
• Purines. XXVIII. Preparation of Some 3,7-Dialkyladenines from 3-Alkyladenines by Alkylation : A Subordinate Formation of 3,9-Dialkyladenines
• Purines. XXI. Synthesis of Adenine 1-Oxides Carrying an Allylic Side Chain at the 9-Position
• Decalcification of Calcium Polycarbophil in Rats
• Structure-Activity Relationship(SAR)Studies on Oxazolidinone Antibacterial Agents.1. Conversion of 5-Substituent on Oxazolidinone
• Cytotoxicity of Organochlorine Pesticides and Lipid Peroxidation in Isolated Rat Hepatocytes
• Cytotoxicity of Organochlorine Pesticides and Lipid Peroxidation in Rat Hepatocytes (Proceedings of the 22nd Symposium on Toxicology and Environmental Health)
• Cytotoxicity of Paraquat and Phospholipid Peroxidation in Rat Hepatocytes (Proceedings of the 21st Symposium on Toxicology and Environmental Health)
• Cytotoxicity of Halogenated Hydrocarbons and Cellular Phospholipid Peroxidation in Isolated Rat Hepatocytes (Proceedings of the 20th Symposium on Toxicology and Environmental Health)
• Characterization of the Neurochemical Effects of N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946) as a Cognition Activator
• P-3 海綿由来アデニン環含有ジテルペノイドの合成研究 : (±)-Agelasimine-Aおよび(±)-Agelasimine-Bの合成(ポスター発表の部)
• Purines. LXV. Preparatory study for the syntheses of the marine sponge purines agelasimines-A and -B: Synthesis and acetylation of their N(7)-benzyl analogues
• Purines. LXIV. Syntheses of 9-Methyl-2-azaadenine 1-Oxide, Its O-Methyl Derivative, and 1-Substituted 5-Azidoimidazole-4-carboxamides
• Purines. LXIII. Syntheses of Azepinomycin, an Antitumor Antibiotic from Streptomyces Species, and Its 3-β-D-Ribofuranodise and Their 8-Imino Analogues
• Purines. LXI. An Attempted Synthesis of 2'-Deoxy-7-methyladenosine : Glycosidic Hydrolyses of the N^6-Methoxy Derivative and 2'-Deoxy N^x-methyladenosines
• Purines. LIX. An Alternative Synthesis of 7-Alkyl-1-methyladenines by Regioselective Alkylation, Fission, and Reclosure of the Adenine Ring
• Purines. LVIII. A Synthesis of 7-Alkyl-1-methyladenines from Adenosine by Regioselective Alkylation : Uilization of a 1-Methoxy Group as a Control Synthon
• Purines. LVII. Regioselective Alkylation of N^6,9-Disubstituted 8-Oxoadenines : Syntheses of the Sea Anemone Purine Caissarone and Some Positional Isomers and Analogues
• Purines. LIV. Intramolecular Cyclization of 9-Ethyl-1-(2-hydroxyethyl)adenine Caused by Nucleophiles : Formation of N^6,1-Ethanoadenine Derivatives
• Purines. LIII. Deamination of 1-(ω-Hydroxyalkyl)adenine Derivatives by Nucleophiles
• Purines. XLIX. Synthesis and Proton Nuclear Magnetic Resonance Study of 3,7-Dialkylxanthines and 1,3,7-Trialkylxanthines
• Purines. XLVIII. Syntheses and Proton Nuclear Magnetic Resonance Study of 2-Deuterioadenines Substituted or Unsubstituted at the 9-Position and of Their N-Oxygenated Derivatives
• Purines. XLVI. Preparation of 1-Ethyladenine from Adenosine
• Immunoliposome-Mediated Gene Transfer into Cultured Myotubes
• Examination of Local Anti-inflammatory Activities of New Steroids, Hemisuccinyl Methyl Glycolates
• Application of Sweet Potato Fiber to Skin Wound in Rat
• Gastroprokinetic Effect of a New Benzamide Derivative Itopride and Its Action Mechanisms in Conscious Dogs
• Synthesis of 5-(Alkylamino)-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamides : Key Intermediates for the Synthesis of 3-Alkyl-9-β-D-ribofuranosylpurine Derivatives
• Purines. XXXII. : Synthesis and Ring Fission of 3,9-Dialkyladenines
• Purines. XXV. Fission and Reclosure of the Adenine Ring by the Use of Modified Benzyloxy Groups at the 1-Position
• Purines. XXII. Methylation of 1-, 3-, 7-, 9-, and N^6-Methyladenines Bearing a Methoxyl Group at the N^6-Position : A Synthesis of 7,9-Dimethyladenine
• Purines. XX. Synthesis of 1-Substituted 5-Aminoimidazole-4-carboxamidines and Related Compounds
• Modification by Fluoride, Bromide, Iodide, Thiocyanate and Nitrite Anions of Reaction of a Myeloperoxidase-H_2O_2-Cl^- System with Nucleosides
• Effects of Fluvastatin and Its Major Metabolites on Low-Density Lipoprotein Oxidation and Cholesterol Esterification in Macrophages
• Fluvastatin, an HMG-CoA Reductase Inhibitor, Protects LDL from Oxidative Modification in Hypercholesterolemic Rabbits
• In Vitro Inhibitory Effects of the Optical Isomers and Metabolites of Fluvastatin on Copper Ion-Induced LDL Oxidation
• An in Vitro Study of the Hydroxyl Radical Scavengin Property of Fluvastatin, and HMG-CoA Reductase Inhibitor
• 2-(3-Pyridyl)thiazolidine-4-carboxamide Derivatives. III. Synthesis of Metabolites and Metabolism of 2-(3-Pyridyl)thiazolidine-4-carboxamides YM461 and YM264 as Platelet-Activating Factor (PAF) Receptor Antagonists
• Purines. XLVII. Dimroth Rearrangement versus Hydrolytic Deamination of 1-Ethyladenine
• Synthesis of [[(Benzenesulfonamido)alkyl]phenyl]alkanoic Acid Derivatives Containing Pyridyl or Imidazolyl Groups and Their Thromboxane A_2 Receptor Antagonistic and Thromboxane A_2 Synthase Inhibitory Activities
• Synthesis of the Selective 5-Hydroxytryptamine 4 (5-HT_4) Receptor Agonist (+)-(S)-2-Chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1,2,4-oxadiazol-3-yl]aniline
• Intramolecular Oxymercuration with Mercuric Triflate
• Mercuric Triflate-TMU Catalyzed Hydration of Terminal Alkyne to give Methyl Ketone under Mild Conditions
• Effects of N-[2-(1-Azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline Fumarate (SK-946), a Novel Cognition Activator, on Learning and Memory in Rodent Models
• Novel 5-Hydroxytryptamine 4 (5-HT_4) Receptor Agonists. Synthesis and Gastroprokinetic Activity of 4-Amino-N-[2-(1-aminocycloalkan-1-yl)ethyl]-5-chloro-2-methoxybenzamides
• Purines. XXXVII. : Synthesis and Reduction of 3,9-Diallkyladenine Salts Deuterated at the 2-Position : Their Use in the Proton Nuclear Magnetic Resonance Study of Isotopically Unmodified Species
• Purines.XXXIX. : The Crystal Structure of 9-Benzyl-N^6-methoxyadenine
• Purines. XXXI. : An X-Ray Crystallographic Structure Analysis of 3-Methyladenosine p-Toluenesulfonate
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. Synthesis and Structure-Activity Relationships of 9-Methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one Derivatives
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. IV. Synthesis and Pharmacological Evaluation of the Oxidation Products of (-)-(R)-5-[(1-Methyl-1H-indol-3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole Hydrochloride (YM060 : Ramosetron)
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. III. Pharmacological Evaluations and Molecular Modeling Studies of Optically Active 4,5,6,7-Tetrahydro-1H-benzimidazole Derivatives
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. II. Synthesis and Structure-Activity Relationships of 4,5,6,7-Tetrahydro-1H-benzimidazole Derivatives
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. I. Synthesis and Structure-Activity Relationships of Conformationally Restricted Fused Imidazole Derivatives
• Purines. XLIV. : A Kinetic Study of the Dimroth Rearrangement of the Marine Sponge Purine 1,9-Dimethyl-8-oxoadenine and Related Compounds
• Purines. XLIII. : A Total Synthesis of the Marine Sponge Base 6-Imino-1,9-dimethyl-8-oxopurine
• 53 桿菌tRNA構成成分,7-Methyladenosineの合成と加水分解(口頭発表の部)
• Purines. XLII. : Synthesis and Glycosidic Hydrolysis of 7-Alkyladenosines Leading to an Alternative Synthesis of 7-Alkyladenines
• Purines. XL. : Preparation of 9-(ω-Carboxyalkyl)-3-methyladenines
• Purines. XXXVI. : Fission and Reclosure of the Adenine Ring in 3,9-Disubstituted Adenines : Effects of Substituents
• Purines. XXXIV. : 3-Methyladenosine and 3-Methyl-2'-deoxyadenosine : Their Synthesis, Glycosidic Hydrolysis, and Ring Fission
• A General and Convenient Synthesis of 7-Alkyladenines from Adenine by Regioselective Alkylation Utilizing Blocking/Deblocking at the 3-Position
• Purines. XXVII. : Hydrolytic Deamination versus Dimroth Rearrangement in the 9-Substituted Adenine Ring : Effect of an ω-Hydroxyalkyl Group at the 1-Position
• Purines. XXVI. The Dimroth Rearrangement of 9-Substituted 1-Methyladenines : Accelerating Effect of a β-D-Ribofuranosyl Group at the 9-Position
• Purines. XXIV. Methylation of N^6-Alkoxyadenines and N^6-Methyladenine
• Purines. XXIII. Synthesis of N^6-Alkoxy-1,3-dialkyladeninium Salts and an Attempt to Synthesize 1,3-Dimethyladenine
• Purines. XIII. Ring Opening of 3-Alkyladenines with Carbobenzoxy Chloride : Transformation into 8-Hydroxylated Adenines
• Purines. X. A Convenient Method for Synthesis of 2', 3'-O-Isopropylidene-adenosine 1-Oxide
• Purines. XVIII. Kinetic Studies of the Dimroth Rearrangement of 1-Alkoxy-9-methyladenines and 1-Benzyloxyadenosine : Effect of 1-Benzyloxy and 9-β-D-Ribofuranosyl Groups on the Rates of the Ring-opening and the Reclosure
• Effect of a Novel Non-steroidal Anti-inflammatory Drug (M-5011) on Cytokine Levels in Rats With Monosodium Urate Crystal-Induced Pleurisy
• Purines. XI. The Synthesis of N-Alkoxyadenosines and Their 2', 3'-O-Isopropylidene Derivatives
• Cytotoxicity of Chlorinated Hydrocarbons and Lipid Peroxidation in Isolated Rat Hepatocytes (Proceedings of the 19th Symposium on Toxicology and Environmental Health)

もっと見る 閉じる

スポンサーリンク