Mass spectrometry-based metabolomics investigation on selected liver cell and mouse models associated with triclosan exposure

Triclosan (TCS) is a synthetic chemical that is extensively used as an anti-bacterial agent in clinical and personal care products. The chemical has been detected in the environment ubiquitously. Environmental exposure to TCS may significantly increase the risk of various diseases. Recent studies have shown that TCS considerably accelerates the development of hepatocellular carcinoma (HCC). Exposure to TCS has been found to enhance liver fibrogenesis and tumorigenesis in mice. TCS exposure-related tumors were detected in mice liver. However, the detailed mechanism of liver toxicity is not well elucidated. Liquid chromatography-mass spectrometry (LC-MS) is a powerful technique for qualitative and quantitative analysis and has been widely employed for metabolomics research. This project will utilize our strong experience in mass spectrometry (MS) and metabolomics research to develop MS-based non-targeted and targeted metabolomics methods and apply for the investigation of the possible influence of triclosan exposure associated with liver disease. TCS exposures at various levels will be investigated in normal human liver cells (LO2) for understanding the toxicological effects, and in liver cancer cell lines (HepG2 and QGY-7703) for evaluating the promoting proliferative effects. The normal C57BL/6 mouse and diethylnitrosamine-induced mouse of HCC model will also be used for investigating the influence of TCS exposures. The difference among groups with or without TCS exposure will be investigated and compared. The change of endogenous metabolites will be analyzed by using LC-Orbitrap high resolution MS and triple quadrupole MS. Multivariate statistics will be used for data analysis. The altered endogenous metabolites induced by TCS will be identified. The metabolic pathways and network will be clarified at metabolism levels. Depending on the identification results of differential metabolites, selected metabolic flux analysis focusing on the interested metabolites in critical pathways (e.g., glycolysis, PPP and derived amino acids or polyamines) will be conducted by using isotope tracer with and without TCS exposure for confirming the identified biomarkers and metabolic pathways and for investigating biochemical mechanism of TCS toxicity. The results from this study may provide insight for the correlation between TCS exposure and the development of liver diseases, and benefit the better understanding of the influences induced by TCS exposure. The successful project completion may also provide valuable information for interpreting the biological effect and toxicological mechanism of TCS.