Comparative effects of deoxycholate and 7-methyl-deoxycholate in the hamster.

HEPATOLOGY(1987)

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摘要
The metabolism and effect on biliary lipids of a new bile acid analog, 7-methyl-deoxycholic acid, were studied and compared with those of deoxycholic acid in the hamster. 14C-Labeled 7-methyl-deoxycholic acid and deoxycholic acid were administered intravenously or intraduodenally to bile fistula hamsters at 1.0 or 4.0 mumoles per min X kg, and hepatic bile was analyzed for radioactive metabolites and biliary lipid outputs. Deoxycholic acid and 7-methyl-deoxycholic acid were efficiently absorbed from the intestine, extracted by the liver and excreted into bile as taurine and glycine conjugates. Twenty per cent of deoxycholic acid was 7 alpha-hydroxylated to cholic acid while 7-methyl-deoxycholic acid did not undergo hydroxylation. During deoxycholic acid infusion, the biliary secretion of phospholipid did not increase, and the bile became more lithogenic. In contrast, 7-methyl-deoxycholic acid stimulated phospholipid secretion, and bile became less lithogenic. Although pathologic changes in the liver were inconstant and mostly mild, both bile acids were toxic in the hamster; hemolysis and death due to respiratory distress were observed.
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