Abstract
Metabonomics, the global analysis of metabolites, have been widely used to identify endogenous metabolites that correlate with a specific physiological state of an organism. Therefore metabonomic profiling is thought to be a powerful tool for following systematic changes associated with metabolic reaction to xenobiotics. In this study, we observed the effects of typical CYP inducers on urinary metabonomic profiles to clarify the effects of CYP induction using mice. And we used two different diets, one was a regular diet for rats and mice and the other was the purified diet, for comparing the effects of chemicals. These diets were fed to C57BL/6JJcl mice before mating. Their offspring were kept on each diet. Dexamethasone (DEX) or 1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was dosed once daily for 3 days to mice at dosage of 100 or 0.3 mg/kg, respectively. Urine of each 8-week-old mouse was collected over a 24-h period. Phosphate buffer solution (pH 7.2) was added to the urine, and the 1H-NMR spectrum was acquired and submitted to Principal Component Analysis (PCA). The results of urinary metabolic profiling showed different classification of treatment in PCA scores plots indicating that there are metabolites variable between control and chemicals treated. PCA loading plots suggested that the level of urinary metabolites including taurine, glucose and trimethylamine were changed. In addition, difference of metabolic profile was observed between control and treated group. Variable levels of these endogenous biomolecules in urine might provide an indirect indicator of hepatic CYP induction in mice.
