Organoselenium (Sel-Plex diet) decreases amyloid burden and RNA and DNA oxidative damage in APP/PS1 mice

Mark A. Lovell, Shuling Xiong, Ganna Lyubartseva, William R. Markesbery

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

To evaluate potential antioxidant characteristics of organic selenium (Se), double knock-in transgenic mice expressing human mutations in the amyloid precursor protein (APP) and human presenilin-1 (PS1) were provided a Se-deficient diet, a Se-enriched diet (Sel-Plex), or a control diet from 4 to 9 months of age followed by a control diet until 12 months of age. Levels of DNA, RNA, and protein oxidation as well as lipid peroxidation markers were determined in all mice and amyloid β-peptide (Aβ) plaques were quantified. APP/PS1 mice provided Sel-Plex showed significantly (P < 0.05) lower levels of Aβ plaque deposition and significantly decreased levels of DNA and RNA oxidation. Sel-Plex-treated mice showed no significant differences in levels of lipid peroxidation or protein oxidation compared to APP/PS1 mice on a control diet. To determine if diminished oxidative damage was associated with increased antioxidant enzyme activities, brain glutathione peroxidase (GSH-Px), glutathione reductase, and glutathione transferase activities were measured. Sel-Plex-treated mice showed a modest but significant increase in GSH-Px activity compared to mice on a normal diet (P < 0.5). Overall, these data suggest that organic Se can reduce Aβ burden and minimize DNA and RNA oxidation and support a role for it as a potential therapeutic agent in neurologic disorders with increased oxidative stress.

Original languageEnglish
Pages (from-to)1527-1533
Number of pages7
JournalFree Radical Biology and Medicine
Volume46
Issue number11
DOIs
StatePublished - Jun 1 2009

Bibliographical note

Funding Information:
This work was supported by NIH Grants 5-P01-AG05119 and 5-P30-AG028383 and by grants from the Abercrombie Foundation and the Healey Family Foundation. The authors thank Ms. Paula Thomason for technical and editorial assistance and Alltech Biotechnology for providing the Sel-Plex diet.

Keywords

  • Alzheimer disease
  • Antioxidants
  • DNA oxidation
  • Free radicals
  • Organoselenium
  • RNA oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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