ダイオキシン低用量暴露母体の肝薬物代謝第二相酵素活性の変動とポリメトキシフラボノイドのin vitro阻害効果

害には，児の成長ホルモンの低下62) や母親のプ

ロラクチンの低下による低育児63) が重要である

1)

が，冒頭にも述べたように，児の甲状腺ホルモン

レベルの低下も一因とされており19)20)，出生後は

児における影響が主と思われるが，胎児期におい

ては母体における甲状腺ホルモンレベル減少に伴

2)

う児での甲状腺ホルモン減少が関与していると考

えられている64)．本研究により in vitro でノビレ

チン及びタンゲレチンが母体肝臓 S9 における

TCDD 誘導性の rUGT1A7 の SN-38 抱合活性を

3)

低下させることが示された．これらの食事由来ポ

リメトキシフラボノイドの摂取が in vivo におい

てもダイオキシン誘導性 UGT1A7 阻害するか否

かは今後の課題である．ノビレチンやタンゲレチ

ンの摂取が，UGT1A7 の適度な阻害を通じた甲状

4)

腺ホルモンの過剰な抱合の抑制，ならびに児にお

ける発育障害の抑制につながることが期待される．

比較的低用量の TCDD（1 m g/kg，p.o.）を妊娠

ラット GD15 に暴露することより GD20 の母体肝

5)

臓において，4-MU，p-NP および SN-38 のグル

クロン酸抱合活性が有意に上昇したことから，

rUGT1A6 および rUGT1A7 の誘導が起こったと

推察された．

ノビレチン及びタンゲレチンは in vitro でダイ

オキシンで誘導された SN-38 抱合活性を有意に

6)

阻害した．

SN-38 抱合活性を rUGT1A7 が触媒する T4 抱

合活性測定の代替と考え，これらのポリメトキシ

フラボノイドが甲状腺ホルモンの過剰な抱合を抑

制し得る食事由来成分として期待された．

これらの食餌由来ポリメトキシフラボノイドの

（ 74 ）

7)

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服部友紀子，武田知起，田浦順樹，黒木広明，石

井祐次，山田英之：ダイオキシン母体曝露によ

る発達児の甲状腺ホルモンへの影響．福岡医誌．

106：127-134，2015．

(Received for publication March 17, 2023)

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