Trihydroxycholanoyl-taurine in brains of rodents with hepatic encephalopathy.

Autor: Schnelle ANW; Department of Chemistry and Biochemistry, Baylor University, Waco, Texas, 76798, USA., Richardson LT; Department of Chemistry and Biochemistry, Baylor University, Waco, Texas, 76798, USA., Pettit ME; Department of Chemistry and Biochemistry, Baylor University, Waco, Texas, 76798, USA.; BioTherapeutics Analytical Development, Janssen Research and Development, LLC, 200 Great Valley Parkway, Malvern, Pennsylvania, 19355, USA., DeMorrow S; Research Services, Central Texas Veterans Health Care System, Temple, Texas, 76504, USA.; Pharmacology and Toxicology Division, College of Pharmacy, University of Texas at Austin, Austin, Texas, 78712, USA.; Department of Internal Medicine, Dell Medical School, University of Texas at Austin, Austin, Texas, 78712, USA., Solouki T; Department of Chemistry and Biochemistry, Baylor University, Waco, Texas, 76798, USA.
Jazyk: angličtina
Zdroj: Journal of mass spectrometry : JMS [J Mass Spectrom] 2021 Jun; Vol. 56 (6), pp. e4729.
DOI: 10.1002/jms.4729
Abstrakt: Hepatic encephalopathy (HE), a neurological disease resulting from liver failure, is difficult to manage and its causes are unclear. Bile acids have been postulated to be involved in the provenance and progression of various diseases including HE. Hence, the characterization of bile acid profiles in the brains of subjects with and without liver failure can provide important clues for the potential treatment of HE. Nanoflow ultra-performance liquid chromatography electrospray ionization ion mobility mass spectrometry (UPLC-ESI-IM-MS) is a highly sensitive method for detection of specific molecules, such as bile acids in brain samples, at biologically relevant concentrations. We used UPLC-ESI-IM-MS to characterize bile acid profiles in brain samples from seven "healthy" control rodents and 22 "diseased" rodents with liver failure (i.e., induced HE). An isomer of trihydroxycholanoyl-taurine was detected in brain tissue samples from both rats and mice with induced HE; however, this isomer was not detected in the brains of healthy rats and mice. Our findings were confirmed by comparing IM arrival times (AT), exact mass measurements (m/z), and mass spectral fragmentation patterns of the experimentally observed suspected species to standards of trihydroxycholanoyl-taurine isomers. Moreover, In Silico Fractionation was employed to provide an additional analytical dimension to verify bile acid identifications.
(© 2021 John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)
Databáze: MEDLINE
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