Effects of Pretreatment of Hep G2 Cells with β-Naphthoflavone on Cytotoxicity of Propranolol and its Active Metabolite 4-Hydroxypropranolol

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概要

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• Cytotoxicities of propranolol (PL) and its active metabolite, 4-hydroxypropranolol (4-OH-PL), were examined in a human hepatoma cell line, Hep G2. Hep G2 cells were cultured in the presence of β-naphthoflavone (BNF, 25 or 50μM), lansoprazole (LPZ, 25 or 50μM) or 0.5% dimethylsulfoxide (vehicle) for 48hr. The cells were harvested, and microsomal and cytosolic fractions were prepared by differential centrifugation methods. Various enzyme activities were determined as follows : microsomal 7-ethoxyresorufin (ER) O-deethylation as a CYP1A1 index, microsomal phenacetin (PN) O-deethylation as a CYP1A2 index, microsomal and cytosolic P-nitrophenyl acetate (NPA) hydrolysis as a carboxylesterase index and cytosolic 4-OH-PL sulfation as a sulfotransferase index. The pretreatment of Hep G2 cells with LPZ or BNF increased microsomal ER O-deethylase activities, and the potency of BNF was much higher than that of LPZ. Cytosolic 4-OH-PL sulfation was also elevated by the pretreatment with BNF but not with LPZ. Microsomal PN O-deethylase activity was not detectable in either the control or BNF-pretreated group under the conditions used. Microsomal and cytosolic NPA hydrolase activities were similar between the control and the BNF-pretreated groups. Cytotoxicities of PL and 4-OH-PL were attenuated in BNF-pretreated Hep G2 cells compared to non-pretreated Hep G2 cells. These results suggest that increased activities of microsomal CYP1Al and cytosolic sulfotransferases by pretreatment with BNF may contribute to the attenuating the cytotoxicity of PL and 4-OH-PL in Hep G2 cells, at least in part.

• 公益社団法人日本薬学会の論文
• 2003-08-01

著者

• WATABE Tadashi

  Department of Molecular Toxicology, Nihon Pharmaceutical University

• NARIMATSU Shizuo

  Laboratories of Health Chemistry,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,

• NAITO Shinsaku

  Research and Development Center, Otsuka Pharmaceutical Factory, Inc.

• Nishimura M

  Research And Development Center Otsuka Pharmaceutical Factory Inc.

• Nishimura Masuhiro

  Department Of Drug Metabolism Division Of Pharmacology Drug Safety And Metabolism Otsuka Pharmaceuti

• Nishimura Masuhiro

  Division Of Pharmacology Drug Safety And Metabolism Otsuka Pharmaceutical Factory Inc.

• Fukumoto Manabu

  Department Of Pathology Institute Of Development Aging And Cancer Tohoku University

• Furukawa M

  Laboratories Of Health Chemistry Faculty Of Pharmaceutical Sciences Okayama University

• Fukuoka Masako

  岡山大学 薬学部 衛生代謝解析学

• OGURA KENICHIRO

  Department of Drug Metabolism and Molecular Toxicology, Tokyo University of Pharmacy and Life Scienc

• Watabe Tadashi

  Department Of Drug Metabolism And Molecular Toxicology Tokyo University Of Pharmacy And Life Science

• UEDA Nobuhiko

  Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc.

• NAITO Shinsaku

  Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc.

• Fukuoka Masako

  Laboratories Of Health Chemistry Faculty Of Pharmaceutical Sciences Okayama University

• Fukumoto Manabu

  Dept. Pathol. Idac. Tohoku Univ.

• Fukumoto M

  First Department Of Pathology School Of Medicine Kyoto University

• Miyano Junko

  Laboratories of Health Chemistry, Faculty of Pharmaceutical Sciences, Okayama University

• Motoyama Harumi

  Laboratories of Health Chemistry, Faculty of Pharmaceutical Sciences, Okayama University

• Yamamoto Shigeo

  Biomolecular Science, Faculty of Pharmaceutical Sciences, Okayama University

• Narimatsu Shizuo

  Laboratories Health Chemistry Faculty Of Pharmaceutical Sciences Okayama University

• Miyano Junko

  Laboratories Of Health Chemistry Faculty Of Pharmaceutical Sciences Okayama University

• Ueda Nobuhiko

  Division Of Pharmacology Drug Safety And Metabolism Otsuka Pharmaceutical Factory Inc.

• Naito S

  Otsuka Pharmaceutical Factory Inc. Tokushima Jpn

• Naito Shinsaku

  Division Of Pharmacology Drug Safety And Metabolism Otsuka Pharmaceutical Factory Inc.

• Ogura Kenichiro

  Department Of Drug Metabolism And Molecular Toxicology School Of Pharmacy Tokyo University Of Pharma

• Ogura Kenichiro

  Department Of Drug Metabolism And Molecular Toxicology School Of Pharmacy Tokyo University Of Pharma

• Ueda Nobuhiko

  Division Of Pharmacology Drug Safety And Metabolism Otsuka Pharmaceutical Factory

• Yamamoto Shigeo

  Biomolecular Science Faculty Of Pharmaceutical Sciences Okayama University

• Motoyama Harumi

  Ina Research Inc.

• Watabe Tadashi

  Department Of Drug Metabolism And Molecular Toxicology School Of Pharmacy Tokyo University Of Pharma

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