Protection of methamphetamine nigrostriatal toxicity by dietary selenium

Hyoung Chun Kim, Wang Kee Jhoo, Dong Young Choi, Doo Hyun Im, Eun Joo Shin, Jeong Hye Suh, Robert A. Floyd, Guoying Bing

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Multiple dose administration of methamphetamine (MA) results in long-lasting toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased production of hydrogen peroxide or other reactive oxygen species in the dopaminergic 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 selenium-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 both the striatum and SN. A novel observation is that MA administration resulted 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 significantly 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 methamphetamine neurotoxicity and that this protection involves GPx-mediated antioxidant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is not yet clear. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)76-86
Number of pages11
JournalBrain Research
Volume851
Issue number1-2
DOIs
StatePublished - Dec 18 1999

Keywords

  • Cu,Zn-superoxide dismutase
  • Dietary selenium
  • Dopamine
  • Glutathione peroxidase
  • Malondialdehyde
  • Methamphetamine-induced neurotoxicity
  • Oxidative stress
  • Ratio of reduced glutathione/oxidized glutathione

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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