Role of deferoxamine on enzymatic stress markers in an animal model of Alzheimer's disease after chronic aluminum exposure.
The effect of the chelator deferoxamine (DFO) on the activity of enzymatic stress markers was assessed in amyloid beta peptide (AβPP) transgenic mice, an animal model of Alzheimer's disease, after oral aluminum (Al) exposure for 6 months. AβPP transgenic (Tg2576) and C57BL6/SJL wild-type mice of 5 months of age were fed a diet supplemented with Al lactate (1 mg of Al/g food). Four groups of Tg2576 and wild-type animals were used: control, Al only, DFO only, and Al plus DFO. Mice in the DFO-treated groups received also subcutaneous injections of 0.20 mmol/kg/d of this chelating agent twice a week until the end of the study at 11 months of age. The hippocampus, cerebellum, and cortex were removed and processed to examine a number of oxidative stress markers. Furthermore, the expression of Cu-Zn superoxide dismutase, glutathione reductase, and catalase was evaluated by quantitative reverse transcriptase polymerase chain reaction analysis. Aluminum levels in the hippocampus of Tg2576 mice were higher than those found in cerebellum and cortex, while the main oxidative effects were evidenced in the presence of DFO only. Oral Al exposure of AβPP transgenic mice would have some potential to promote pro-oxidant events, while DFO administration would not help in preventing these deleterious effects.
Esparza
José L
JL
Laboratory of Toxicology and Environmental Health, IISPV, School of Medicine Universitat Rovira i Virgili, Catalonia, Spain.
Garcia
Tania
T
Gómez
Mercedes
M
Nogués
M Rosa
MR
Giralt
Montserrat
M
Domingo
José L
JL
D000535:Aluminum / Q000008:administration & dosage / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002614:Chelating Agents / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013312:Stress, Physiological / Q000502:physiology*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002614:Chelating Agents; D000535:Aluminum; D003676:Deferoxamine