Journal article
UHPLC-MS-Based lipidomic and metabonomic investigation of the metabolic phenotypes of wild type and hepatic CYP Reductase Null (HRN) mice
Journal of Pharmaceutical and Biomedical Analysis, Vol.186, Art. 113318
2020
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.
Details
- Title
- UHPLC-MS-Based lipidomic and metabonomic investigation of the metabolic phenotypes of wild type and hepatic CYP Reductase Null (HRN) mice
- Authors/Creators
- N. Gray (Author/Creator) - Division of Computational and Systems Medicine, Dept. of Metabolism, Digestion and Reproduction, Imperial College, London, SW7 2AZ, UK; Australian National Phenome Centre, Health Futures Institute, Murdoch University, Perth, WA, Australia.L.A. Gethings (Author/Creator) - Waters (United States)R.S. Plumb (Author/Creator) - Waters (United States)I.D. Wilson (Author/Creator) - Imperial College London
- Publication Details
- Journal of Pharmaceutical and Biomedical Analysis, Vol.186, Art. 113318
- Publisher
- Elsevier
- Identifiers
- 991005544732207891
- Copyright
- © 2020 Elsevier B.V.
- Murdoch Affiliation
- Australian National Phenome Centre; Health Futures Institute
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Industry collaboration
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- Citation topics
- 2 Chemistry
- 2.211 Mass Spectrometry
- 2.211.990 Metabolomics
- Web Of Science research areas
- Chemistry, Analytical
- Pharmacology & Pharmacy
- ESI research areas
- Pharmacology & Toxicology