Cytoprotective effect of vitamin E against D-galactosamine-induced cell death is more related to transcriptional than antioxidant regulatory properties in cultured human hepatocytes

The aim of the present study was to determine if the regulation of oxidative stress by vitamin E is related to its cytoprotective properties against D-GalN-induced cell death in cultured human hepatocytes. Liver samples were obtained from surgery of hepatic tumors. Vitamin E (50 M) was added 10 h after D-GalN (40 mM). D-GalN induced oxidative stress, apoptosis and necrosis in cultured human hepatocytes. This citotoxic effect of D-GalN was associated with a raise of inducible nitric oxide synthase (NOS-2), CYP3A4 and CYP3A5, but reduced PPAR-alpha, PXR and CPTI-A expression. Vitamin E reduced D-GalN-induced cell death without modification of intracellular oxidative stress. Vitamin E reduced NF-kB activation and NOS-2, but increased CYP3A4, CYP3A5, PPAR-alpha, PXR and CPT1-A expression in D-GalN-treated hepatocytes.