Ischemic insult induced apoptotic changes in PC12 cells: Protection by trans resveratrol

In this study, we determined the protective potential of trans resveratrol against oxygen-glucose deprivation (OGD) induced reactive oxygen species mediated apoptotic damages in PC12 cells. In vitro model of ischemic cerebral stroke was created by keeping cells in an OGD condition for 6 h followed by 24 h reoxygenation. Cells received biologically safe doses (5, 10, and 25 mu M) of trans resveratrol in the following schedules for 24 h prior to OGD; during 6 h of OGD; for 24 h post OGD and whole treatment group which starts from 24 h before OGD and lasted to 24 h post OGD. Anti-ischemic potential of trans resveratrol was assessed by measuring the regulation of lipid peroxidation, reactive oxygen species production, glutathione content, and expression (mRNA and protein) of apoptotic markers such as Bax, Bcl(2) and Caspase-3. Hypoxia inducible factor-1 alpha (HIF-1 alpha) was also assessed to correlate the changes with ischemic injuries. Significant (P<0.05) restoration in lipid peroxidation, reactive oxygen species, and glutathione content were observed following the treatment of trans resveratrol in cells receiving OGD and re-oxygenation. Changes induced by trans resveratrol could be correlated well with alterations in the expression of Bax, Bcl(2), Caspase-3 and HIF-1 alpha. These results indicate that trans resveratrol administration attenuates free radical formation and mitochondria mediated apoptosis perhaps by regulating the expressions of Bax, Bcl(2), and Caspase-3 in PC12 cells receiving OGD and re-oxygenation insult. (C) 2011 Elsevier B.V. All rights reserved.