An integrated metabonomic method for profiling of metabolic changes in carbon tetrachloride induced rat urine

Carbon tetrachloride (CCl4) is a well-known model compound for inducing chemical hepatic injury. This work characterizes the metabolism disorders of hepatotoxicity induced by CCl4 in a Wistar rat model with a single dosage of 1 ml/kg. A seven-day long continuous collection of urine was performed in male rats in this experiment. Blood biochemistry and histopathology were examined to identify specific changes of liver hepatotoxicity. At the same time, an integrated analytical approach based on liquid chromatography coupled with mass spectrometry (LC-MS) was developed to map the metabolic response in urine. The current metabonomic approach based on LC-MS indicated 23 endogenous metabolites as biomarkers in urine associated with the hepatotoxicity induced by CCl4. The underlying regulations Of CCl4-perturbed metabolic pathways were discussed according to the identified metabolites. The present study proves the great potential of LC-MS based metabonomics in mapping metabolic response for toxicology. (C) 2008 Elsevier Ireland Ltd. All rights reserved.