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The primary objective of this study was to discover biomarkers which are correlated with hepatotoxicity induced by chemicals using 1 H NMR spectral data of urine. A procedure of nuclear magnetic resonance (NMR) urinalysis using pattern recognition was proposed for early screening of the hepatotoxicity of CCl 4 , acetaminophen (AAP), and D-galactosamine (GalN) in rats. The hepatotoxic compounds were expected to induce necrosis in hepatocytes. This was confirmed through blood biochemistry and histopathology. CCl 4 (1 ml/kg, po) or GalN (0.8 g/kg, ip) was single administered to Sprague-Dawley (S-D) rats and urine was collected every 24 h. Animals were sacrificed 24 h or 48 h post-dosing. AAP (2 g/kg, po) was administered for 2 days and then the animals were sacrificed 24 h after the last treatment. NMR spectroscopy revealed evidently different clustering between control groups and hepatotoxicant treatment groups in global metabolic profilings as indicated by partial least square (PLS)-discrimination analysis (DA). In targeted profilings, endogenous metabolites of allantoin, citrate, taurine, 2-oxoglutarate, acetate, lactate, phenylacetyl glycine, succinate, phenylacetate, 1-methylnicotinamide, hippurate, and benzoate were selected as putative biomarkers for hepatoxicity by CCl 4 , AAP, and GalN. Comparison of our rat 1 H NMR PLS-DA data with histopathological changes suggests that 1 H NMR urinalysis can be used to predict hepatotoxicity induced by CCl 4 , AAP, and GalN.

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