Comparison of metabolic profiles from serum from hepatotoxin-treated rats by nuclear-magnetic-resonance-spectroscopy-based metabonomic analysis.

Hepatotoxicities were induced in rats using alpha-naphthylisothiocyanate (ANIT), carbon tetrachloride (CCl(4)), and hydrazine (HYD). Male Wistar rats were treated with three typical hepatotoxins, and serum samples were collected after 48 h. Biochemical effects of these toxins on plasma composition were evaluated by high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy of serum. The biochemical effects of CCl(4) were characterized by an elevated level of 3-d-hydroxybutyrate (HB), acetoacetate (Aca), and creatinine (Cn) in serum, and ANIT led to increases in the amounts of low-density lipoprotein (LDL), alanine, acetate, glycoprotein, succinate, Cn, acetone, 3-d-hydroxybutyrate, and Aca. For the HYD-treated group, LDL, HB, acetate, and Cn were obviously increased in serum. The region delta 0.0-10.0 of each spectrum was segmented into 0.04 ppm. The area under the spectrum was calculated for each segmented region and expressed as an integral value. After removal of the water signal (delta 4.6-5.0) the remaining 235 intensity-related descriptors were used for the pattern recognition analysis. Principal component analysis was used to visualize the similarities and differentiations in biochemical profiles of serum from the rats treated with various hepatotoxins. This work showed the power of the combination of NMR and pattern recognition for the study of biochemical effects of xenobiotics.