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  • Title: Dosage effects of resveratrol on ethanol-induced cell death in the human K562 cell line.
    Author: Chan WH, Chang YJ.
    Journal: Toxicol Lett; 2006 Feb 08; 161(1):1-9. PubMed ID: 16125344.
    Abstract:
    Previous studies have established that ethanol induces cell apoptosis and necrosis. However, the precise molecular mechanisms are currently unclear. Here, we show that higher concentrations of ethanol (250-400 mM) induced a shift from apoptotic to necrotic cell death in human K562 cells, and that resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties, inhibited or enhanced ethanol-induced apoptosis/necrosis depending on the treatment dosage. Using the cell permeable dye 2',7'-dichlorofluorescin diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation, we showed that ethanol treatment directly increased intracellular oxidative stress. This intracellular oxidative stress increased in response to high concentrations (100-200 microM) of resveratrol, but remained unchanged following treatment with low concentrations (10-25 microM) of resveratrol. Further studies showed that resveratrol could attenuate or enhance ethanol-induced intracellular oxidative stress generation-dependent on treatment dosage, and that this effect could be correlated with cell apoptosis or necrosis. Importantly, ethanol-induced changes in intracellular ATP levels were also correlated with resveratrol dosage. Taken together, these results indicate that the treatment dosage may determine the effect of resveratrol on ethanol-induced ROS generation, intracellular ATP levels, and cell apoptosis or necrosis. Thus our findings support the possibility that appropriate dosage of resveratrol aids in decreasing the toxic effect of ethanol.
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