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Relationship between serum and biliary bile acids as an indicator of chenodeoxycholic and ursodeoxycholic acid-induced hepatotoxicity in the rhesus monkey

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Abstract

The relationship between serum and biliary concentrations of bile acids was studied in 20 rhesus monkeys which developed hepatotoxicity after six months of treatment with 40 and 120 mg/kg/day doses of chenodeoxycholic (cheno) and ursodeoxycholic (urso) acids, respectively. During the treatment, lithocholate—all of which was unsulfated—increased several-fold both in serum and in bile. There was a significant correlation between serum and biliary concentrations of lithocholate. Similarly close correlations existed between the serum and biliary concentrations of the conjugates of cheno and urso which increased during treatment with the respective bile acids. The serum levels of cholate and deoxycholate remained normal, although their concentrations in bile decreased considerably during treatment with cheno and urso, respectively. Further studies have to establish whether serum determinations of lithocholate can also be used in man to study the role of this bile acid in the liver function abnormalities which develop in some patients treated with cheno or urso and/or whether measurement of serum cheno and urso could be useful for the monitoring of patient compliance with the respective bile acid treatment.

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The study was supported in part by grant AM-19689 from the National Institutes of Health. Dr. Fromm is recipient of Research Career Development Award AM-00290 from the National Bazzoli is a Research Fellow in Gastroenterology sponsored by the National Council of Research, Rome, Italy, and by NATO.

The skillful technical assistance of Prafulla Amin and Susan Ceryak is gratefully acknowledged.

A preliminary report of this work was published in abstract form inGastroenterology (78:1301, 1980).

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Bazzoli, F., Roda, A., Fromm, H. et al. Relationship between serum and biliary bile acids as an indicator of chenodeoxycholic and ursodeoxycholic acid-induced hepatotoxicity in the rhesus monkey. Digest Dis Sci 27, 417–424 (1982). https://doi.org/10.1007/BF01295650

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  • DOI: https://doi.org/10.1007/BF01295650

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