Synaptosomal response to oxidative stress: Effect of vinpocetine

It has been suggested that reactive oxygen species (ROS) play a role in the neuronal damage occurring in ischemic injury and neurodegenerative disorde rs and that their neutralization by antioxidant drugs may delay or minimize neurodegeneration. In the present study we examine whether vinpocetine can act as an antioxidant and prevent the formation of ROS and lipid peroxidat ion in rat brain synaptosomes. After ascorbate/Fe2+ treatment a significant increase in oxygen consumption (about 5-fold) and thiobarbituric acid reac tive substances (TBARS) formation (about 7-fold) occurred as compared to co ntrol conditions. Vinpocetine inhibited the ascorbate/Fe2+ stimulated consu mption of oxygen and TBARS accumulation, an indicator of lipid peroxidation , in a concentration-dependent manner. The ROS formation was also prevented by vinpocetine. Oxidative stress increased significantly the fluorescence of the probes 2',7'-dichlorodihydrofluorescein (DCFH2-DA) (about 6-fold) an d dihydrorhodamine (DHR) 123 (about 10-fold), which is indicative of intras ynaptosomal ROS generation. Vinpocetine at 100 mu M concentration decreased the fluorescence of DCFH2-DA and DHR 123 by about 50% and 83%, respectivel y. We conclude that the antioxidant effect of vinpocetine might contribute to the protective role exerted by the drug in reducing neuronal damage in p athological situations.