The potential of metabolomic approaches for investigating mode(s) of action of xenobiotics: Case study with carbon tetrachloride

Both experimental animals and humans exhibit complex cellular responses upon exposure to xenobiotics and may undergo similar types of metabolic changes leading to adverse outcomes. Exposure to xenobiotics results in perturbation of many cellular events (e.g. oxidative stress, lipid peroxidation, inflammation, genotoxicity, cytotoxicity, etc.), and during this process biochemicals (endogenous metabolites) of a given metabolic pathway are increased, decreased or unaffected. Metabolomics is an emerging medium to high-throughput technology that can automatically identify, quantify and characterize hundreds to thousands of low molecular weight biochemicals simultaneously, using targeted or global analytical approaches, yielding a metabolic fingerprint and understanding of biochemical pathway perturbations. Herein, we illustrate how metabolomics can be utilized to explore the mechanisms of action of xenobiotics which affect different ‘key events’ contributing to different mode(s) of action. The extensively studied hepatotoxicant carbon tetrachloride (CCl4) is specifically described.