title: Vinpocetine and α-tocopherol prevent the increase in DA and oxidative stress induced by 3-NPA in striatum isolated nerve endings.
abstract: Vinpocetine is a neuroprotective drug that exerts beneficial effects on neurological symptoms and cerebrovascular disease. 3-nitropropionic acid (3-NPA) is a toxin that irreversibly inhibits succinate dehydrogenase, the mitochondrial enzyme that acts in the electron transport chain at complex II. In previous studies in striatum-isolated nerve endings (synaptosomes), we found that vinpocetine decreased dopamine (DA) at expense of its main metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and that 3-NPA increased DA, reactive oxygen species (ROS), DA-quinone products formation, and decreased DOPAC. Therefore, in this study, the possible effect of vinpocetine on 3-NPA-induced increase in DA, ROS, lipid peroxidation, and DA-quinone products formation in striatum synaptosomes were investigated, and compared with the effects of the antioxidant α-tocopherol. Results show that the increase in DA induced by 3-NPA was inhibited by both 25 μM vinpocetine and 50 μM α-tocopherol. Vinpocetine, as α-tocopherol, also inhibited 3-NPA-induced increase in ROS (as judged by DCF fluorescence), lipid peroxidation (as judged by TBA-RS formation), and DA-quinone products formation (as judged by the nitroblue tetrazolium reduction method). As in addition to the inhibition of complex II exerted by 3-NPA, 3-NPA increases DA-oxidation products that in turn can inhibit other sites of the respiratory chain, the drop in DA produced by vinpocetine and α-tocopherol may importantly contribute to their protective action from oxidative damage, particularly in DA-rich structures.
authors.affiliation: Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México.
authors.forename: Nieves
authors.initials: N
authors.lastname: Herrera-Mundo
authors.forename: María
authors.initials: M
authors.lastname: Sitges
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects*; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D009411:Nerve Endings / Q000737:chemistry / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D014748:Vinca Alkaloids / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D000975:Antioxidants; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D014748:Vinca Alkaloids; C013983:vinpocetine; D024502:alpha-Tocopherol; C015392:3-nitropropionic acid; D004298:Dopamine