Integrative Metabonomic Study On Tamoxifen-and Flutamide-induced Hepatotoxicity

In this study, an GC-MS based intergrated metabonomic method was used to analyze metabolite profiling in the serum and liver of rats and also in HepG2cell to investagate mechanism of tamoxifen-and flutamide-induced hepatotoxicity.(1) A metabonomic approach was used to investigate the mechanisms of tamoxifen-induced liver injury. In vivo, we analysised liver extracts and serum obtained from the Wistar rats that exposed to three doses of tamoxifen; In vitro, we also analysised metabolites in the HepG2cell exposed to different doses of tamoxifen. And then an integrative analysis of the data from metabonomic both in vivo and in vitro was performed, combines to biochemical results as refernces. The results suggested that tamoxifen can cause oxidative stress and a deleption of sugars and amino acids in the liver and HepG2cell, which can lead to an elevation of some fatty acids in the liver by absorbing lipid in peripheral. This is why tamoxifen can induced hepatotoxicity.(2) A metabonomic approach was also used to investigate the mechanisms of fiutamide-induced liver injury. In vivo, we analysised liver extracts and serum obtained from the Wistar rats that exposed to three doses of flutamide; In vitro, we also analysised metabolites in the HepG2cell exposed to different doses of flutamide. And then an integrative analysis of the data from metabonomic both in vivo and in vitro was performed, combines to biochemical results as refernces. The results suggested that flutamide can result in oxidative both in vivo and in vitro, which can make the red cell membrane decomposed and the level of bilirubin increased. This is why flutamide can induced icterohepatitis.