Metabolomic analysis of urethane-induced lung carcinogenesis in rats and the ameliorative effect of Qi-Yu-San-Long decoction†

Abstract

Lung carcinogenesis (LC) is a kind of disease, which threatens human health seriously. Metabolomic research on bio-fluids and tissues is crucial for elucidating the pathogenesis of LC and understanding the therapeutic mechanisms of medicines. In this study, we established a rat model for LC by induction with urethane. The anti-tumor effect of Qi-Yu-San-Long decoction (QYSLD) on LC was assessed through morphology changes, histopathological examination, and inflammation levels. Utilizing the metabolomics technique based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), we investigated the metabolic changes in the plasma and lungs of LC rats and explored the ameliorative effects of QYSLD on the molecular levels. Functional biomarkers associated with QYSLD in LC rats were identified and relatively quantified. The results manifested that, in contrast to the control group, the number of tumor nodules and inflammation levels in the LC model group increased significantly, indicating that the LC rat model was successfully built. After QYSLD treatment, the morphology and lesion degree of LC rats were greatly improved. A total of 23 differential metabolites between the control group and the urethane-induced LC group were screened through plasma and lung tissue metabolomics studies, of which 20 were considerably modulated after QYSLD treatment. Metabolic pathway analysis revealed that the pathogenesis of LC and the therapeutic effects of QYSLD primarily involved glycerophospholipid metabolism, ether lipid metabolism, sphingolipid metabolism, and arachidonic acid metabolism. Our findings provide a potential intracellular metabolite profile for urethane-induced LC and demonstrate that QYSLD exerts anti-tumor effects on LC by modulating multiple metabolic pathways.