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 disorders 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 peroxidation in rat brain synaptosomes. After ascorbate/Fe2+ treatment a significant increase in oxygen consumption (about 5-fold) and thiobarbituric acid reactive substances (TBARS) formation (about 7-fold) occurred as compared to control conditions. Vinpocetine inhibited the ascorbate/Fe2+ stimulated consumption 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) and dihydrorhodamine (DHR) 123 (about 10-fold), which is indicative of intrasynaptosomal ROS generation. Vinpocetine at 100 microM concentration decreased the fluorescence of DCFH2-DA and DHR 123 by about 50% and 83%, respectively. We conclude that the antioxidant effect of vinpocetine might contribute to the protective role exerted by the drug in reducing neuronal damage in pathological situations.
Santos
M S
MS
Department of Zoology and Faculty of Medicine, Center for Neurosciences of Coimbra, University of Coimbra, Portugal.
Duarte
A I
AI
Moreira
P I
PI
Oliveira
C R
CR
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014748:Vinca Alkaloids / Q000494:pharmacology*
D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D014748:Vinca Alkaloids; D002084:Butylated Hydroxytoluene; C013983:vinpocetine; D001205:Ascorbic Acid; D010100:Oxygen