title: Intact Endogenous Metabolite Analysis of Mice Liver by Probe Electrospray Ionization/Triple Quadrupole Tandem Mass Spectrometry and Its Preliminary Application to in Vivo Real-Time Analysis.
abstract: Probe electrospray ionization (PESI) is a recently developed ionization technique that enables the direct detection of endogenous compounds like metabolites without sample preparation. In this study, we have demonstrated the first combination use of PESI with triple quadrupole tandem mass spectrometry (MS/MS), which was then applied to intact endogenous metabolite analysis of mice liver, achieving detection of 26 metabolites including amino acids, organic acids, and sugars. To investigate its practicality, metabolic profiles of control and CCl4-induced acute hepatic injury mouse model were measured by the developed method. Results showed clear separation of the two groups in score plots of principal component analysis and identified taurine as the primary contributor to group separation. The results were further validated by the established gas chromatography/MS/MS method, demonstrating the present method's usefulness. In addition, we preliminarily applied the method to real-time analysis of an intact liver of a living mouse. We successfully achieved monitoring of the real-time changes of two tricarboxylic acid cycle intermediates, α-ketoglutaric acid and fumaric acid, in the liver immediately after pyruvic acid injection via a cannulated tube to the portal vein. The present method achieved an intact analysis of metabolites in liver without sample preparation, and it also demonstrates future possibility to establish in vivo real-time metabolome analysis of living animals by PESI/MS/MS.
authors.affiliation: In Vivo Real-Time Omics Laboratory, Institute for Advanced Research, Nagoya University , Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.|Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Zaitsu
authors.affiliation: In Vivo Real-Time Omics Laboratory, Institute for Advanced Research, Nagoya University , Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.|Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-8673, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Shimadzu Corporation , 1 Nishinokyo-Kuwabaracho, Nakagyo-ku, Kyoto, 604-8511, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-8673, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ohara
authors.affiliation: Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-8673, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakagiri
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Kusano
authors.affiliation: Shimadzu Corporation , 1 Nishinokyo-Kuwabaracho, Nakagyo-ku, Kyoto, 604-8511, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: College of Life and Health Sciences, Chubu University , 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine , 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-8673, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuchihashi
authors.affiliation: Department of Legal Medicine & Bioethics, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishii
mesh_terms: D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D002241:Carbohydrates / Q000032:analysis*; D002251:Carbon Tetrachloride; D002264:Carboxylic Acids / Q000032:analysis*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation; D053719:Tandem Mass Spectrometry / Q000295:instrumentation; D013997:Time Factors
chemical_list: D000596:Amino Acids; D002241:Carbohydrates; D002264:Carboxylic Acids; D002251:Carbon Tetrachloride