胆汁うっ滞および肝障害におけるリガンディンとBSPの肝内動態について
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概要
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It is generally accepted that ligandin has an important role in intracellular transport of many kinds of chemicals involving organic anions, bilirubin, steroid hormones and drugs metabolized in the liver. In this report, we investigated the changes in amounts of ligandin and their BSP-binding activity using cholestatic and liver-injured rats. Cholestasis was induced in rats by administration of alpha naphthylthioisocyante (ANIT) or by common bile duct ligation. Liver injury was induced by injection of D-galactosamine (i.p.) . Cholestasis and liver injury were confirmed by measuring serum bilirubin, total cholesterol, alkaline phosphatase and GPT. These values were markedly increased after 24 hrs of ANIT treatment and ligation. Amounts of ligandin were found to be increased after 24 hrs. of ANIT administration and 48 hrs. of ligation. On the other hand, after 48 hrs of the ANIT and 24 hrs. of the ligation, ligandin increased 17% and 28% of the control value, respectively. Amounts of BSP bound to ligandin isolated from ANIT-treated and ligated liver cytosol were drastically decreased. The specific activities of BSP binding to ligandin prepared from ANIT-treated and ligated rats were almost half those of the control. Since liver cytosol fractions from ANIT-treated and ligated rats contained the same amounts of protein and BSP, it was considered that the low specific activity under cholestasis was due to the decrease of binding capacity of liganding by increasing organic anions in the cytosol. In the case of liver injury by D-galactosomine, the specific activity of BSP-binding was normal, even though the amounts of protein and BSP in the cytosol were markedly decreased. This result suggested that liver cells from galactosamine-treated rats were affected on protein synthesis, including liganding and/or plasma membrane, but not on characteristics of BSP-binding of ligandin.
- 学校法人 昭和大学・昭和医学会の論文
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