Metabolism and cholestatic effect of 3α-hydroxy-7ζ-methyl-5β-cholanoic acid
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3α-Hydroxy-7ζ-methyl-5β-cholanoic acid (7ζ-methyl-LA) was infused intravenously into bile fistula hamsters to investigate its metabolism and effect on the bile flow as compared with lithocholic acid. Following infusion of the labeled bile acids, bile was collected quantitatively to allow measurement of bile flow and bile acid composition. More than 80% of radioactivity was recovered in bile within 4 hr. 7ζ-Methyl-LA and lithocholic acid in bile were present as the taurine and glycine conjugates; no free bile acids were detected. 7ζ-Methyl-LA was neither hydroxylated nor metabolized to any measurable extent, though lithocholic acid was 7α-hydroxylated to chenodeoxycholic acid (30–45%).
At the infusion rate at which lithocholic acid induced a severe cholestasis (264 nmol/min), 7ζ-methyl-LA did not decrease the bile flow. In fact, the infusion of 7ζ-methyl-LA produced a mild choleresis under conditions where endogenous bile acid excretion was not changed appreciably compared to control infusions with albumin.
It is concluded that 7ζ-methyl-LA is not metabolized in the hamster but is conjugated with taurine and glycine, and that the introduction of a methyl group at the 7-position of lithocholic acid appears to alleviate the cholestatic effect of lithocholic acid in the hamster.
KeywordsBile Acid Taurine Cholestasis Cholic Acid Bile Flow
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