CYP2E1-mediated modulation of valproic acid-induced hepatocytotoxicity
作者： Manuela G Neuman , Neil H Shear , Pearl M Jacobson-Brown , Gady G Katz , Heather K Neilson
DOI: 10.1016/S0009-9120(01)00217-X
关键词: Chemistry 、 CYP2E1 、 Metabolite 、 Pharmacology 、 Apoptosis 、 Necrosis 、 Cytokine 、 Toxicity 、 Hep G2 、 Cytotoxicity
摘要: Abstract Objectives: To determine the cytotoxicity of valproic acid (VPA) and its metabolite, 4-ene-valproic (4-ene-VPA) in human hepatoblastoma cells (Hep G2), to study modulatory effect cytochrome P450 2E1 induction this model. Methods: Cells were exposed VPA or 4-ene-VPA presence either ethanol (EtOH), EtOH combined with disulphiram (DS). Some α-fluoro-VPA α-fluoro-4-ene-VPA absence CYP2E1 inducers. Apoptosis necrosis measured by analyzing 6000 per sample using transmission electron microscopy, while cytokine release apoptosis quantitated ELISA. Results: + increased cytotoxicity. significantly toxicity, DS reduced toxicity. Alpha-fluorinated analogues compared corresponding compounds. Neither nor α–fluorinated IL-6 TNF-α media. A significant increase was observed that further exposure. Conclusions: experience greater than those treated VPA. Cytochrome inducers enhance toxicity VPA-exposed cells, α-fluorination diminishes directly interfering β-oxidation metabolite.
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