Comparative effects of deoxycholate and 7‐methyl‐deoxycholate in the hamster

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 ham...

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Veröffentlicht in:Hepatology (Baltimore, Md.) Md.), 1987-03, Vol.7 (2), p.229-234
Hauptverfasser: Kuroki, Syoji, Mosbach, Erwin H., Stenger, Richard J., Cohen, Bertram I., McSherry, Charles K.
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Sprache:eng
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Zusammenfassung: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 μmoles per min·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 7α‐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.
ISSN:0270-9139
1527-3350
DOI:10.1002/hep.1840070205