Metabonomics Study On The Usnic Acid And Erthromycin Estolate-induced Liver Toxicity By GC-MS

As a holistic research strategy, metabonomics has been applied to drug safety assessment, disease diagnosis, and some other research areas. Gas chromatography-mass spectrometry (GC-MS) technique is one of the commonly used analysis technics in metabonomics, which is characterized by high resolution and sensitivity, with a commercialized MS database for rapid identification of metabolites. In this study, a gas chromatography-mass spectrometry method combined with pattern recognition approaches was applied to profile the metabolic composition of biofluids from rat. And then, the possible toxicity mechanism of usnic acid and erythromycin estolate-induced liver injury was tentatively clarified.(1) A GC-MS-based integrated metabonomic approach was applied to investigate the mechanisms of usnic acid-induced liver injury by examining plasma and liver tissue extracts obtained from the rats repeatedly exposed to different doses of usnic acid. Serum biochemical analysis and histopathological examinations were simultaneously performed. The results showed that usnic acid exposure can lead to disturbances in energy metabolism, amino acid metabolism, lipid metabolism and nucleotide metabolism, which are attributable to usnic acid toxicological effects on the liver. And the degree of injury depends on the dose of usnic acid.(2) The same GC-MS-based metabonomics analysis technique was used to study the alterations of serum and liver metabolite profiles in rats after exposure to erythromycin estolate. In this investigation, according to the results of the pattern recognition analysis (PCA and PLS-DA), the differences between the metabolic phenotypes were better described. The hepatotoxic mechanism of erythromycin estolate was associated with the degradation of protein, fat, hexose and nucleic acid according to the results. And a dose-depend hepatotoxic result was also seen from the study.Moreover, our findings from the two studies support the fact that metabonomic analysis is more sensitive than conventional histopathology and serum biochemical analysis.