HYPOLIPIDEMIC EFFECT AND ENHANCEMENT OF PEROXISOMAL β-OXIDATION IN THE LIVER OF RATS BY SODIUM-(E)-3-(4-(3-PYRIDYLMETHYL) PHENYL)-2-METHYL PROPENOATE (OKY-1581), A POTENT INHIBITOR OF TxA_2 SYNTHETASE
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概要
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The effects of sodium-(E)-3-(4-(3-pyridylmethyl) phenyl)-2-methyl propenoate (OKY-1581) and (E)-3-(4-(imidazolylmethyl)phenyl)-2-propenoic acid (OKY-046), potent inhibitors to thromboxane A_2 synthetase, on peroxisomal β-oxidation and on lipid levels of liver and serum in the rat were studied. When the animals were administered with OKY-1581 at the dose levels of 100 and 500 mg/kg body weight for 2 weeks, the activity of peroxisomal β-oxidation increased 2.2-and 6.3-fold respectively. Catalase activity increased 1.3-fold, whereas D-amino acid oxidase (DAAO) and urate oxidase activities did not change. Carnitine acetyltransferase and carnitine palmitoyltransferase activities also increased 2.2- - 4.1-fold and 2.7- - 4.2-fold respectively. These changes of the enzymes related to lipid metabolism were also confirmed by the results of a cell fractionation study. Moreover, the induction of peroxisome proliferation-associated polypeptide having a molecular weight of 80000,which is a bifunctional enzyme in the peroxisomal β-oxidation system was also observed electrophoretically in the light mitochondrial fraction of the liver of OKY-1581-treated rat. The contents of triglyceride and cholesterol in the serum decreased. These results indicated that the action of OKY-1581 in enhancing hepatic peroxisomaloxidation is similar to that of a potent hypolipidemic peroxisome proliferator such as clofibrate. On the other hand, differing from OKY-1581,OKY-046 at the dose level of 500 mg/kg for 2 weeks showed no effect on serum and liver lipid levels and on the activities of the peroxisomal enzymes, including a cyanide-insensitive fatty acyl-CoA oxidizing system and carnitine acetyl transferase.
- 公益社団法人日本薬学会の論文
著者
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WATANABE Takafumi
Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Science
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SUGA Tetsuya
Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Scien
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Watanabe T
Department Of Clinical Biochemistry Tokyo College Of Pharmacy:laboratory Of Molecular Biology Azabu
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Suga T
Dept. Clin. Biochem. Sch. Pharm. Sci. Tokyo College Of Pharmacy
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Suga Tetsuya
Department Of Clinical Biochemistry Faculty Of Pharmaceutical Science Tokyo University Of Pharmacy A
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Suga Tetsuya
Department Of Clinical Biochemistry Tokyo College Of Pharmacy:laboratory Of Molecular Biology Azabu
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Suga T
Department Of Clinical Biochemistry School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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Fujitani H
Azabu Univ. Sagamihara‐shi Jpn
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Fujitani H
Azabu Univ. Sagamihara Jpn
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Fujitani Hideo
Laboratory Of Molecular Biology Azabu University School Of Veterinary Medicine
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MITSUKAWA MIWAKO
Department of Clinical Biochemistry, Tokyo College of Pharmacy
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UTSUGI MAKOTO
Department of Clinical Biochemistry, Tokyo College of Pharmacy
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Utsugi Makoto
Department Of Clinical Biochemistry Tokyo College Of Pharmacy
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Watanabe Takafumi
Department Of Aerospace Engineering Osaka Prefecture University
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Mitsukawa Miwako
Department Of Clinical Biochemistry Tokyo College Of Pharmacy:department Of Development Morishita Ph
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Watanabe Takafumi
Department Of Clinical Biochemistry Tokyo College Of Pharmacy:laboratory Of Molecular Biology Azabu
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