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Bile acid conjugation in the chimpanzee: effective sulfation of lithocholic acid

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Abstract

To characterize the hepatic biotransformation in the chimpanzee of the primary bile acid chenodeoxycholic acid (chenic) and its major bacterial metabolite lithocholic acid (lithocholic) a mixture of tracer amounts of14C-lithocholic and3H-chenic was injected intravenously into two animals with a bile fistula; the chemical form of radioactivity appearing in bile was inferred using thin layer chromatography. About 80% of chenic, and 70% of lithocholic was recovered in 90 min. Chenic was completely conjugated in bile, appearing predominantly as chenyltaurine (52%) and chenylglycine (37%). An unidentified conjugate (about 11%) was also found. Lithocholic was excreted completely as taurine and glycine conjugates, but the majority (63%) of conjugates was sulfated. Sulfation increased progressively with time, and lithocholylglycine was sulfated more than lithocholyltaurine. We conclude that the chimpanzee is similar to man in that the secondary bile acid lithocholic is efficiently sulfated. The chimpanzee thus differs from the baboon and rhesus monkey which sulfate lithocholic poorly. However, the chimpanzee differs from man and is similar to the baboon and rhesus monkey in showing preferential conjugation of bile acids with taurine. The results imply that hepatotoxicity caused by chenic, which is well documented in the rhesus monkey and baboon and has been related to defective lithocholic sulfation, should not occur in the chimpanzee.

Zusammenfassung

Um im Schimpansen die hepatische Biotransformation der primären Gallensäure Chenodeoxycholsäure und deren wichtigstem bakteriellen Metaboliten, Lithocholsäure zu charakterisieren, wurde ein Gemisch aus Spurenmengen von14C-Lithocholsäure und3H-Chenodeoxycholsäure intravenös in zwei Tiere mit Gallenfistel injiziert. Die chemische Form der Radioaktivität, die in der Galle erschien, wurde dünnschichtchromatographisch ermittelt. Etwa 80% der Chenodeoxycholsäure und 70% der Lithocholsäure wurden innerhalb von 90 min ausgeschieden. Die Chenodeoxycholsäure war vollständig konjugiert und erschien vorwiegend als Chenyltaurin (52%) und Chenylglycin (37%). 11% erschienen in einer Form, die bisher nicht identifiziert wurde. Lithocholsäure wurde vollständig als Taurin- und Glycinkonjugat in die Galle eliminiert; der größte Teil (63%) war zusätzlich sulfatiert. Die Sulfatierung nahm stetig mit der Zeit zu und Lithocholylglycine wurde stärker sulfatiert als Lithocholyltaurin.

Wir schließen aus diesen Befunden, daß der Schimpanse mit dem Menschen vergleichbar ist, indem er Lithocholsäure effektiv sulfatiert. Dadurch unterscheidet sich der Schimpanse vom Rhesusaffe und Baboon, die die Lithocholsäure nur in geringem Maße sulfatieren. Jedoch unterscheidet sich der Schimpanse auch vom Menschen und ähnelt dem Rhesusaffen und dem Baboon, indem er Gallensäure vorwiegend mit Taurin konjugiert. Die Ergebnisse lassen den Schluß zu, daß die Hepatotoxizität, die im Rhesusaffe und Baboon durch Chenodeoxycholat hervorgerufen wird, und auf eine geringe Sulfatierung der Lithocholsäure zurückgeführt wird, beim Schimpansen nicht bestehen sollte.

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Author notes

  1. A. F. Hofmann

    Present address: U.S. Senior Scientist Awardee Alexander von Humboldt Foundation, Department of Medicine, University of California at San Diego, USA

Authors and Affiliations

  1. Institut für Toxikologie, Gesellschaft für Strahlen- und Umweltforschung, D-8042, Neuherberg, Federal Republic of Germany

    M. Schwenk & H. Greim

  2. Gastroenterology Unit, Mayo Clinic and Mayo Foundation, 55901, Rochester, Minnesota, USA

    G. L. Carlson & J. A. Carter

  3. Institute of Comparative and Human Toxicology, Albany Medical College, 47 New Scotland Avenue, 12208, Albany, N.Y., USA

    F. Coulston

Authors
  1. M. Schwenk
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  2. A. F. Hofmann
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  3. G. L. Carlson
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  4. J. A. Carter
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  5. F. Coulston
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  6. H. Greim
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The work was supported by GSF, as well as Mayo Foundation, Alexander von Humboldt Foundation and Grant AM 16770

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Schwenk, M., Hofmann, A.F., Carlson, G.L. et al. Bile acid conjugation in the chimpanzee: effective sulfation of lithocholic acid. Arch Toxicol 40, 109–118 (1978). https://doi.org/10.1007/BF01891965

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