The goal of this study was to investigate the effect of resveratrol, an active ingredient found in grapes and other plant products, in ameliorating oxidative stress. Oxidative stress was induced by addition of Fe2+ and t-butyl hydroperoxide to the cultured PC12 cell medium. Resveratrol, vitamins C and/or E, were added to the cell culture medium during oxidative stress. The combination of resveratrol and vitamins C and/or E was more effective in protecting the cell than was any of these three antioxidants alone.

Oxidative stress in the central nervous system (CNS) may cause oxidation of lipoprotein particles. The oxidized lipoproteins may damage cellular and subcellular membranes, leading to tissue injury and cell death. Human low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) are oxidized by transition metal ions, such as Cu2+. Using PC 12 cells, we tested the cytotoxicity of oxidized LDL and VLDL. Cell death was increased in a dose-dependent manner. Antioxidants added to the incubation medium, such as vitamins E or C, or resveratrol showed some protection. Results indicated that oxidized lipoproteins may serve as an oxidative stressor, which may initiate the neuronal cell death leading to the manifestation of Alzheimer disease (AD).

Oxidative stress in the central nervous system may cause oxidation of lipoproteins. The oxidized lipoproteins may in turn damage cellular and subcellular membranes and other biomolecules, leading to tissue injury and cell death. Recently, we have demonstrated that oxidized LDL and VLDL induced cell death in a dose-dependent manner. The present study examined the possible signal transduction cascade leading to cell death by oxLDL and oxVLDL in PC12 cells. Using the electrophoretic mobility shift assay, we found that both oxLDL and oxVLDL activated the binding of NF-kappaB to the consensus sequence in the promoter region of the target genes, followed by apopototic cell death. Resveratrol protects the cells from both the activation of NF-kappa-B/ DNA binding activity and apoptotic cell death. Results indicated that oxidized lipoproteins may serve as an oxidative mediator and may activate apoptosis through a nuclear signalling pathway contributing to the pathology in Alzheimer's disease.

No abstract

Increased oxidative stress in the brain due to chronic ethanol consumption is known to result in a number of neurodegenerative changes. This study was designed to test whether dietary supplementation of grape polyphenols (GP) can offer protection to the neurodegenerative changes resulting from chronic ethanol consumption. Sprague-Dawley rats were fed a Leiber-DeCarli liquid diet with ethanol or isocaloric amount of maltose, and with or without GP for 2 months. Chronic ethanol caused significant decreases in synaptosomal Na,K-ATPase (20.5%) and dopamine uptake (22.8%) activities compared with pair-fed controls. Although GP alone did not alter activities of these membrane-bound proteins, GP supplementation was able to completely protect the decrease in synaptic protein function elicited by chronic ethanol consumption.