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UHPLC-MS-Based lipidomic and metabonomic investigation of the metabolic phenotypes of wild type and hepatic CYP reductase null (HRN) mice

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Title: UHPLC-MS-Based lipidomic and metabonomic investigation of the metabolic phenotypes of wild type and hepatic CYP reductase null (HRN) mice
Authors: Gray, N
Gethings, LA
Plumb, RS
Wilson, ID
Item Type: Journal Article
Abstract: Hepatic cytochrome P450 reductase (EC 1.6.2.4, POR) deficient mice provide a useful means of investigating liver-related CYP450 drug metabolism. However, the organ-wide inactivation of CYP450s has wide ranging effects on liver physiology. Untargeted UHPLC-MS metabolic and lipid profiling of aqueous and organic solvent extracts has been employed to compare the metabolic phenotypes of livers obtained from either wild type (C57Bl6) or hepatic P450 reductase null (HRNTM) mice. The metabolic phenotyping of polar aqueous extracts revealed differences between wild type and HRNTM mice for bile acids with taurochendeoxycholic acid, and tauroursodeoxycholic acid increased in proportion in the latter and taurocholic acid reduced. Lipidomic profiling demonstrated that there were numerous differences in the lipidome, particularly relating to phospholipid synthesis with significant changes in the relative amounts of phosphatidylcholines (PC) and phosphatidylethanolamines (PE). These results illustrate the wide ranging disruptive effects on the normal hepatic phenotype that result from POR-deficiency in the the HRNTM animals.
Issue Date: 15-Jul-2020
Date of Acceptance: 14-Apr-2020
URI: http://hdl.handle.net/10044/1/79198
DOI: 10.1016/j.jpba.2020.113318
ISSN: 0731-7085
Publisher: Elsevier BV
Start Page: 1
End Page: 9
Journal / Book Title: Journal of Pharmaceutical and Biomedical Analysis
Volume: 186
Copyright Statement: © 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Analytical Chemistry
0301 Analytical Chemistry
1115 Pharmacology and Pharmaceutical Sciences
Publication Status: Published online
Article Number: 113318
Online Publication Date: 2020-04-18
Appears in Collections:Department of Surgery and Cancer
Faculty of Medicine