Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress

  • Long Yue
    Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University Department of Anesthesiology, 163th Hospital of PLA
  • Dong Xin
    Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University
  • Yuan Yawei
    Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University
  • Huang Jinqiang
    Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University
  • Song Jiangang
    Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University
  • Sun Yumin
    Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University
  • Lu Zhijie
    Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University
  • Yang Liqun
    Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University
  • Yu Weifeng
    Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University

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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, LysoPCc (14:0), glycine and succinic acid and decreased levels of l-valine, PCb (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.

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