Metabolism of 2,2ʼ,3,4,4ʼ,5,6ʼ-Heptachlorobiphenyl (CB182) by Rat, Guinea Pig and Human Liver Microsomes

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  • Ohta Chiho
    Faculty of Nutritional Sciences, Nakamura Gakuen University
  • Fujii Yukiko
    Daiichi College of Pharmaceutical Sciences
  • Haraguchi Koichi
    Daiichi College of Pharmaceutical Sciences
  • Kato Yoshihisa
    Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University
  • Kimura Osamu
    Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido
  • Endo Tetsuya
    Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido
  • Koga Nobuyuki
    Faculty of Nutritional Sciences, Nakamura Gakuen University

Bibliographic Information

Other Title
  • 2,2ʼ,3,4,4ʼ,5,6ʼ-七塩素化ビフェニル（CB182）のラット，モルモットおよびヒト肝ミクロゾームによる代謝
  • 2,2',3,4,4',5,6'-七塩素化ビフェニル(CB182)のラット,モルモットおよびヒト肝ミクロゾームによる代謝
  • 2,2',3,4,4',5,6'-ナナ エンソカ ビフェニル(CB182)ノ ラット,モルモット オヨビ ヒト カン ミクロゾーム ニ ヨル タイシャ

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Abstract

The in vitro metabolism of 2,2ʼ,3,4,4ʼ,5,6ʼ-heptachlorobiphenyl (CB182) by rat, guinea pig and human liver microsomes was compared and the effects of cytochrome P450 (CYP) inducers, phenobarbital (PB) and 3-methylcholanthrene (MC), on CB182 metabolism were examined. Only one metabolite was produced by rat, guinea pig and human liver microsomes and the order of the activity was rat (PB-treated)＞＞ guinea pig (PB-treated)＞ guinea pig (untreated, MC-treated)＞ human ＞ rat (untreated). Pretreatment of PB resulted in the remarkable increase of the metabolite in rats (1,370 pmol/hr/mg protein) and a slight increase in guinea pigs (27 pmol/hr/mg protein). In contrast, MC treatment to rats and guinea pigs decreased M-1. By comparison of GC-MS data of the methylated M-1 with a synthesized authentic sample, M-1 was determined to be 3ʼ-hydroxy (OH)-CB182. These results suggest that 3ʼ-OH-CB182 is a major metabolite formed by PB-inducible CYP2B enzymes in both animals and rat CYP2B enzymes possess much higher activity to hydroxylate CB182 than guinea pig and human CYP2B enzymes.

Journal

  • 福岡醫學雜誌

    福岡醫學雜誌 108 (3), 51-57, 2017-03-25

    Fukuoka Medical Association

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