ウサギにおけるリトコール酸およびその硫酸抱合体の肝毒性

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The hepatotoxic effects of lithocholylglycine (LCG) and sulfolithocholylglycine (SLCG) were investigated in male rabbits intravenously injected for 7 days with 2 and 20 mg/kg of LCG and SLCG, respectively. GPT, GOT, ALP and leucine aminopeptidase (LAP) activities were measured on days 2,4 and 7 after the start of the treatments and on day 7 the liver was studied microscopically and the bile acid composition in plasma, urine and gallbladder bile were determined. In the 20 mg/kg LCG group, GPT activities were markedly elevated, in one rabbit (No. 8), GOT, ALP and LAP activities were also elevated. Histopathologically, focal necrosis of liver cells, portal infiltration of round cells, hypertrophy of ductular cells, proliferation of bile ducts and an increase in connective tissue around bile ducts were found. Plasma concentrations of lithocholic acid (LC) and sulfated LC were increased, as was urinary excretion of sulfated LC. In rabbit No. 8,the increase of sulfated LC in plasma and urine was marked and the sulfate-percentage of LC was more than 95%. Moreover, urinary excretion of deoxycholic-, cholic- and chenodeoxycholic acid was markedly higher than in other animals. No clear changes of bile acid concentration and composition in gallbladder bile were detected. In the 2 mg/kg LCG group and in the SLCG groups, no hepatotoxic changes were noted biochemically or histopathologically, and no changes in the bile acid pattern were observed.
公益社団法人日本薬学会の論文
1980-08-25

ウサギにおけるリトコール酸およびその硫酸抱合体の肝毒性

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