LC/MS-based non-targeted metabolomics for the investigation of general toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J and DBA/2J mice

Although numerous studies have been performed for the toxicological mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the metabolic changes of TCDD toxicity is less well understood. In this study, liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/QTOFMS) was used for non-targeted metabolomics for understanding the different metabolic patterns associated with TCDD exposure in aryl hydrocarbon receptor (AhR) sensitive C57BL/6J (C6) and less sensitive DBA/2J (D2) mouse strains. The serum samples were analyzed and treated with metabolomic analysis in conjunction with multivariate data analysis. Metabolite identification was performed with interpreting high resolution MS data and MS/MS fragmentation, searching against databases and comparing with authentic compounds. Twelve differentiating metabolites (defined as a ≥1.5-fold change with a P ≤ 0.001) were highlighted in C6 mice versus control group, revealing lipid accumulation, fatty acid beta-oxidation, inflammation and alteration of amino acids as well as phase II drug-like metabolism. In contrast, only 2 differentiating metabolites were detected in D2 mouse model.