Identification of the Potential Metabolic Pathways Involved in the Hepatic Tumorigenesis of Rat Diethylnitrosamine-Induced Hepatocellular Carcinoma via 1H NMR-Based Metabolomic Analysis

The systemic investigation of the metabolic pathways associated with the hepatic tumorigenesis is important to discover novel biomarkers and identify the potential pathogenesis. Here, the 1H nuclear magnetic resonance- (1H NMR-) based metabolomic analysis was used to monitor the whole process of rat diethylnitrosamine-induced HCC. Intraperitoneal administration of diethylnitrosamine (DEN) was used to induce primary HCCs in male Sprague-Dawley rats. Magnetic resonance imaging (MRI) examinations were performed to follow the tumor formation and growth in the liver and HE OPLS-DA models and corresponding VIP plots analysis further identified ten metabolites associated with the abnormal metabolism. The aberrant glucose, lipid, and glutathione-glutamine-glutamate metabolism could be detected involving in the process of hepatic tumorigenesis, which provides an important evidence for the in-depth study of subsequent molecular mechanisms, especially the glutathione-glutamine-glutamate metabolism.