NMR spectroscopic-based metabonomic investigation on the acute biochemical effects induced by Ce(NO3)3 in rats

An integrated metabonomic approach based on high-resolution 1H NMR spectroscopy has been applied to the investigation of the acute biochemical effects caused by Ce(NO3)3 in rats. Male Wistar rats were separated into 8 groups and each was treated with one of following compounds, mercury II chloride (HgCl2), 2-bromoethanamine hydrobromide (BEA), carbon tetrachloride (CCl4), α-naphthylisothiocyanate (ANIT), and three doses of Ce(NO3)3 (i.p. 2, 10 and 50 mg/kg body weight). Urine was collected over a 48-h time course, and serum and tissue samples (liver and kidney) were gained after exposure to Ce(NO3)3 for 48 h. Histopathology and plasma clinical chemistry were also performed for all the tissue and plasma samples. Urine and serum samples were analyzed by 600 MHz 1H NMR spectroscopy. All the 1H NMR spectra were data-processed and analyzed using principal components analysis or hierarchical clustering analysis to show the time- and dose-dependent biochemical variations induced by Ce(NO3)3. Metabolic profiles of urinary 1H NMR spectra from animals treated with Ce(NO3)3 exhibited an increase in trimethylamine N-oxide (TMAO), dimethylamine (DMA), dimethylglycine (DMG), taurine (Tau) and amino acids (valine, leucine and isoleucine), together with a decrease in citrate. The 1H NMR spectral analysis of serum presented the elevation of acetone, acetoacetate, lactate and creatinine levels. These findings indicated the impairment of fatty acid β-oxidation in liver mitochondria and renal lesions. This work illustrates the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by rare earths.