Protective potential of trans-resveratrol against 4-hydroxynonenal induced damage in PC12 cells.

The role of 4-hydroxynonenal (4-HNE), a byproduct of membrane lipid peroxidation has been suggested in neurodegeneration. However, the underlying mechanisms are poorly understood. The investigations were carried out to study the preventive potential of trans-resveratrol against 4-HNE induced damage in PC12 cells. Trans-resveratrol, a natural compound obtained from grape skin and found in red wine, is reported to have wide pharmacological window. Cells pretreated with trans-resveratrol (5, 10 and 25 microM) for 24 h were exposed to 4-HNE (25 microM) for 2 h. Pre-treatment of trans-resveratrol was found to be significantly effective in countering the cytotoxic responses of 4-HNE. Significant reduction in reactive oxygen species generation, restoration of intracellular glutathione, and lipid peroxidation levels suggest the improved antioxidant defense system in the cells pretreated with trans-resveratrol. Further, 4-HNE induced alterations in the protein expression of mitochondria-mediated apoptosis markers (Bax, Bcl-2 and Caspase-3) were significantly restored by pre-treatment of trans-resveratrol suggesting the protective potential of trans-resveratrol in PC12 cells against 4-HNE induced oxidative damage. Together these data show the prophylactic potential of trans-resveratrol in oxidative stress mediated apoptotic neurodegeneration.