1. Academic Validation
  2. Metabolism of obeticholic acid in brown bullhead (Ameiurus nebulosus)

Metabolism of obeticholic acid in brown bullhead (Ameiurus nebulosus)

  • Environ Sci Pollut Res Int. 2019 Jul;26(20):20316-20324. doi: 10.1007/s11356-019-05398-2.
Samuel Mach 1 2 Alexandr Jegorov 3 Zdeněk Šimek 4
Affiliations

Affiliations

  • 1 Teva Czech Industries s.r.o., Ostravská 29, 747 70, Opava, Czech Republic. samuel.mach@tevapharm.cz.
  • 2 RECETOX, Masaryk University Brno, Kamenice 126/3, 625 00, Brno, Czech Republic. samuel.mach@tevapharm.cz.
  • 3 Teva Czech Industries s.r.o., Ostravská 29, 747 70, Opava, Czech Republic.
  • 4 RECETOX, Masaryk University Brno, Kamenice 126/3, 625 00, Brno, Czech Republic.
Abstract

Analysis of brown bullhead (Ameiurus nebulosus) bile by ultra performance liquid chromatography high-resolution mass spectrometry (UPLC/HRMS) revealed a series of bile acids similar to those found in humans. Accordingly, we chose this fish as a model organism to examine the metabolism of obeticholic acid, a bile acid used to treat a number of human liver diseases and the one that has the potential to occur as an environmental contaminant. The taurine and glycine conjugates of obeticholic acid and keto-obeticholic acid were identified, as well as the D-cysteinolic acid conjugate of obeticholic acid, likely a metabolite specific to fish. In addition, metabolites of obeticholic acid (sulphate and glucuronide) and several hydroxy-obeticholic acid derivatives were found, representing typical pathways of primary and secondary steroid metabolism. Brown bullhead exposed to obeticholic acid at a dose of 100 mg/kg gave no overt signs of distress or toxicity.

Keywords

Ameiurus nebulosus; Fish; Metabolites; Obeticholic acid; UPLC/HRMS.

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