ラットのジメチルニトロサミン誘発急性肝障害に対するプロスタグランジンＥ１・α‐シクロデキストリン包接化合物（ＰＧＥ１・ＣＤ）の抑制効果

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  • Inhibitory effects of prostaglandin E1.ALPHA.-cyclodextrin (PGE1CD) on dimethylnitrosamine-induced acute liver damage in rats.
  • ラット ノ ジメチルニトロサミン ユウハツ キュウセイ カン ショウガイ ニ

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The effects of PGE1CD on dimethylnitrosamine (DMN)-induced acute liver damage with intravascular coagulation in rats were biochemically and histopathologically investigated. PGE1·CD was administered i.v. from 30 min before to 24 hr after DMN-intoxication (pretreatment) and from 30 min after or from 4 hr after to 24 hr after DMN-intoxication (post-treatment). Pretreatment with PGE1·CD (0.2-2 μg/kg/min) dose-dependently suppressed the decrease of platelet counts and the elevation of blood biochemical parameters (PT, HP T, GOT, GPT, LDH, LAP, T-Bil) caused by DMN-intoxication. PGE1·CD (0.51 μg/kg/min and over) significantly suppressed the DMN-induced histopathological changes (occurrence of hemorrhage and necrosis). Post-treatment with PGE1·CD (2 μg/kg/min) also suppressed the liver damage. Furthermore, pretreatment with PGE1·CD (2 μg/kg/min) not only suppressed the disruption of hepatocytes, but also prevented the damages of sinusoidal endothelial cells and lysosomal membrane, and it reduced the increase of lipid peroxidation. PGE1·CD (1 μg/kg/min and over) significantly suppressed the decrease of hepatic tissue blood flow caused by DMN-intoxication. These results demonstrate that PGE1·CD has therapeutically efficacy against DMN-induced acute liver damage in rats; Therefore, it will be clinically useful for the treatment of severe hepatitis such as fulminant hepatitis with intravascular coagulation in the sinusoid.

収録刊行物

  • 日本薬理学雑誌

    日本薬理学雑誌 105 (4), 221-229, 1995

    公益社団法人 日本薬理学会

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