NMR-Based metabonomics combined with clinical biochemical analysis and histopathological examination was applied to investigate the toxicity effects of vanadyl sulfate with insulin-like activity in male Wistar rats. Male Wistar rats were administrated with VOSO₄ at doses of 15 and 45 mg/kg body weight by intragastric administration for 16 d. Urine and serum samples were collected and analyzed by ¹H NMR experiment. Multivariate analyses were employed to identify the characteristic metabolites for the toxicity effects of vanadyl sulfate. Then the metabolic networks of these characteristic metabolites were built up using TICL (a web Tool for automatic Interpretation of Compound List). The relationship between the characteristic metabolites and the main matebolic pathways perturbed were analyzed and discussed. The differences of metabolic profiles were examined among high-dose (45 mg/kg), low-dose (15 mg/kg) of VOSO₄ and control groups. Compared to the control group, increased levels of lactate, creatinine and taurine in serum and increased excretion of trymethylamine-N₂-oxide, creatinine, taurine and glycine in urine were found in both high- and low-dose groups which showed an obvious dose-dependent relationship. On the other hand, the concentration of acetate and succinate were decreased in both serum and urine samples of dosed groups. These results indicate that VOSO₄ have disturbed the carbohydrate metabolism, lipid metabolism and gut microflora and the high-dosage of VOSO₄ may cause liver and kidney injury.

Key words: nuclear magnetic resonance (NMR), metabonomics, toxicity, vanadyl sulfate, a web tool for automatic interpretation of compound list (TICL)