Organoselenium (Sel-Plex diet) decreases amyloid burden and RNA and DNA oxidative damage in APP/PS1 mice.
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 beta-peptide (Abeta) plaques were quantified. APP/PS1 mice provided Sel-Plex showed significantly (P<0.05) lower levels of Abeta 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 Abeta 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.
Lovell
Mark A
MA
Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA. malove2@email.uky.edu
Xiong
Shuling
S
Lyubartseva
Ganna
G
Markesbery
William R
WR
D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D004249:DNA Damage; D004789:Enzyme Activation; D005247:Feeding Behavior; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009422:Nervous System Diseases / Q000178:diet therapy; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D058225:Plaque, Amyloid / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D012313:RNA / Q000032:analysis
D016564:Amyloid beta-Protein Precursor; D016566:Organoselenium Compounds; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012313:RNA; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase