薬物の胎子毒性に関する薬理学的研究　ＶＩＩ　　サリチル酸の胎子毒性に対する発熱物質の増強作用

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タイトル別名
  • Studies on the pharmacological bases of fetal toxicity of drugs (VII).
  • ヤクブツ ノ タイシ ドクセイ ニ カンスル ヤクリガクテキ ケンキュウ 7
  • サリチル酸の胎仔毒性に対する発熱物質の増強作用

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We reported previously that the acute and fetal toxicities of aspirin (ASA) were enhanced by bacterial endotoxin (LPS). In order to clarify the mechanism of the enhancement by LPS, the effects of LPS on the toxicities of salicylic acid (SA), the main metabolite of ASA, were investigated in rats. The following results were obtained: 1) The acute toxicity of SA was significantly potentiated by LPS in male rats. The LD50 of SA with LPS was about one third of that of SA alone. 2) The increase of maternal body weight was inhibited significantly after administration of SA (383 mg/kg, p.o.) with LPS (20 μg/kg, i.v.), but not after administration of SA alone. 3) The fetal toxicity of SA including fetal death, resorption, growth retardation and skeletal variations was slightly observed in the dam receiving a single dose of SA on the 15th day of pregnancy, but it was markedly increased by LPS (20 μg/kg, i.v.). 4) The half-life period of SA in plasma was increased significantly by the coadministration of LPS in male rats after administration of ASA or SA. All of these phenomena in the rats given SA closely resembled the phenomena previously reported in the rats given ASA. These results suggest that SA might play a main role in the acute and fetal toxicities of ASA, and one of the mechanism of the enhancement effect by LPS on ASA-induced fetal toxicity might be related to the increase of SA concentration in the fetus.

収録刊行物

  • 日本薬理学雑誌

    日本薬理学雑誌 84 (5), 411-416, 1984

    公益社団法人 日本薬理学会

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