Objective to study the effects of Z24 on the metabonomic profile of rat plasma and its relationship with blood biochemical
indicators and
histopathology,explore the feasibility of metabonomics in the application of early
toxicity screening of drug candidate.Methods 20 femal Wistar rats were administrated orally with 0,60,130 and 200 mg/kg Z24 for 5 days respectively.After dosing, plasma was collected and its 1H nuclear magnetic resonance(NMR) spectra were acquired and all animals were taken blood biochemical analysis and liver histopathology examination.Results The plasma alanine aminotransferase(ALT),aspartate transaminase(AST),total bilirubin(Tbil) level of 200 mg/kg group rats were increased by 148.4%, 140% and 109.8% compared to controls respectively. There were clear necrosis foci in liver histopathology of 200 mg/kg and 130 mg/kg groups. And the plasma metabonomic approach could readily distinguish the Z24 dosed toxicity, with a good agreement between clinical chemistry, microscopically examination and partial-least-squares discriminant analysis(PLS-DA) data. And PLS-DA analysis suggested effects at low doses, which were not as evident by clinical chemistry or microscopic analysis.Conclusion The effect of Z24 on the rat plasma metabonomic profile is related with Z24 toxicology which supports the contention that the metabonomic approach represents a promising new technology for the development of a rapid throughput in vivo toxicity screening tool.