title: Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress.
abstract: The study examined the global metabolic and some biochemical changes in rats with cholestasis induced by bile duct ligation (BDL). Serum samples were collected in male Wistar rats with BDL (n = 8) and sham surgery (n = 8) at day 3 after surgery for metabolomics analysis using a combination of reversed phase chromatography and hydrophilic interaction chromatography (HILIC) and quadrupole-time-of-flight mass spectrometry (Q-TOF MS). The serum levels of malondialdehyde (MDA), total antioxidative capacity (T-AOC), glutathione (GSH) and glutathione disulfide (GSSG), the activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) were measured to estimate the oxidative stress state. Key changes after BDL included increased levels of l-phenylalanine, l-glutamate, l-tyrosine, kynurenine, l-lactic acid, LysoPC(c) (14:0), glycine and succinic acid and decreased levels of l-valine, PC(b) (19:0/0:0), taurine, palmitic acid, l-isoleucine and citric acid metabolism products. And treatment with BDL significantly decreased the levels of GSH, T-AOC as well as SOD, GSH-Px activities, and upregulated MDA levels. The changes could be mapped to metabolism of amino acids and lipids, Krebs cycle and glycolysis, as well as increased oxidative stress and decreased antioxidant capability. Our study indicated that BDL induces major changes in the metabolism of all 3 major energy substances, as well as oxidative stress.
authors.affiliation: Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, China ; Department of Anesthesiology, 163th Hospital of PLA, Hunan 410003, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Jinqiang
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yu
keywords: HILIC-MS; RPLC-MS; metabolomics; obstructive jaundice; oxidative stress