Protection of methamphetamine nigrostriatal toxicity by dietary selenium

Citation
Hc. Kim et al., Protection of methamphetamine nigrostriatal toxicity by dietary selenium, BRAIN RES, 851(1-2), 1999, pp. 76-86
Citations number
61
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
0006-8993 → ACNP
Volume
851
Issue
1-2
Year of publication
1999
Pages
76 - 86
Database
ISI
SICI code
0006-8993(199912)851:1-2<76:POMNTB>2.0.ZU;2-#
Abstract
Multiple dose administration of methamphetamine (MA) results in long-lastin g toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased p roduction of hydrogen peroxide or other reactive oxygen species in the dopa minergic system. The present study was designed to determine the protective effects of dietary antioxidant selenium on MA-induced neurotoxicity in the nigrostriatal dopaminergic system. Male C57BL/6J mice were fed either sele nium-deficient (<0.01 ppm Se) or selenium-replete (0.2 ppm Se) diets for 90 days. MA treatment decreased the dopamine (DA) levels in the striatum and substantia nigra (SN) of both Se-replete and Se-deficient animals. However, in Se-replete animals, this DA depletion was significantly attenuated in b oth the striatum and SN. A novel observation is that MA administration resu lted in increased activity of Cu,Zn-SOD in the brains of both Se-deficient and Se-replete animals. However, MA administration to Se-deficient animals exhibited a higher Cu,Zn-SOD activity in the nigrostriatal system than the control animals. Elevated malondialdehyde (MDA) levels in the striatum and SN were also observed in Se-deficient MA-treated animals. Se repletion sign ificantly increased the glutathione peroxidase (GPx) activity and the ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) in the MA-treated animals. In conclusion, we have shown that dietary Se attenuated methamphe tamine neurotoxicity and that this protection involves GPx-mediated antioxi dant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is no t yet clear. (C) 1999 Elsevier Science B.V. All rights reserved.