| In this study, a metabonomic method that based on gas chromatography-mass spectrometry (GC-MS) combine pattern recognition approach, as well as a genechip based toxicogenomic approach were used to clarfy the possible toxicity mechanisms of tetracycline hydrochloride-and erythromycin estolate-induced liver injury.(1) A GC-MS based metabonomic approach and a genechip based toxicogenomic approach were applied to investigate the mechanisms of tetracycline hydrochloride-induced liver injury, by analysing liver extracts obtained from the rats that exposed to different doses of tetracycline hydrochloride, as well as extracts obtained from the rat hepatocyte exposed to tetracycline hydrochloride. Serum biochemical analysis and histopathological examinations were also performed. And then integrative analysis of the data from metabonomic and toxicogenomic was performed, referring to biochemical and histopathological results as references. The results suggested that tetracycline hydrochloride exposed can lead to changes in p53 signaling pathway and cell cycle, as well as DNA injury in liver. Also disturbances happened in protein metabolism, fat metabolism and carbohydrate metabolism.(2) The same toxicogenomic approach above was applied to study liver extracts from rats those exposed to different doses of erythromycin estolate. We analyzed the microarray results, referring to metabonomic data, serum biochemical results and histopathological results which obtained from the same rats before. The results showed that erythromycin estolate-induced liver injury and dysfunction is likely not only due to the oxidative stress, but also due to the transporter-based cholestasis, and following cell cycle arrest and DNA damage in the livers.Moreover, our findings suggest that systems toxicology method, such as metabonomics and transcriptomics, combine serum biochemical and histopathological analysis is an effective approach to study drug-induced liver injury. |
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