Abstract |
The metabolism of intravenously infused bile salts, tauroursodeoxycholate, tauro-beta-muricholate and their corresponding unconjugated forms in the liver was investigated in bile salt-depleted bile fistula rats. The biliary bile salt composition was determined by gas chromatography-mass spectrometry using chemical positive ionization and electron-impact methods. For an infusion rate of 2 micromol/min/kg, all bile salts were efficiently secreted in bile, inducing similar choleresis. Only tauroconjugated bile salts were recovered; no glucuronide or glyco derivatives were detected. The infusion of free ursodeoxycholate led to the appearance of a metabolite identified as a Delta22 derivative (12%). A similar biotransformation rate (11%) was observed following free beta-muricholate infusion. In contrast, no metabolite was observed after infusion of the tauroconjugated form of ursodeoxycholate and beta-muricholate. The unsaturation process probably depends on the availability of the carboxyl group for the starting step of the beta-oxidation mechanism. In conclusion, the current in vivo study demonstrates a hepatic origin for Delta22 bile salts. It also shows that free bile salts were sensitive to Delta22 formation while conjugation with taurine totally prevented the side-chain oxidation of the two 7beta-hydroxylated bile salts.
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Authors | Mustapha Guitaoui, Michel Parquet, Claude Aubert, Anne-Marie Montet, Jean-Claude Montet |
Journal | Fundamental & clinical pharmacology
(Fundam Clin Pharmacol)
Vol. 18
Issue 4
Pg. 457-64
(Aug 2004)
ISSN: 0767-3981 [Print] England |
PMID | 15312152
(Publication Type: Journal Article)
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Chemical References |
- Bile Acids and Salts
- Taurine
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Topics |
- Animals
- Bile Acids and Salts
(deficiency, metabolism)
- Biliary Fistula
(metabolism)
- Biotransformation
- Gas Chromatography-Mass Spectrometry
- Liver
(drug effects, metabolism)
- Male
- Rats
- Rats, Sprague-Dawley
- Taurine
(pharmacology)
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