Role of Deferoxamine on Enzymatic Stress Markers in an Animal Model of Alzheimer’s Disease After Chronic Aluminum Exposure

Abstract

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.

Protective effect of apple (Ralls) polyphenol extract against aluminum-induced cognitive impairment and oxidative damage in rat

“…Aluminum (Al) is a well-known neurotoxic agent, which has been involved in neuro-disorders such as Alzheimer's disease (AD) and other serious neurodegenerative diseases (Esparza et al, 2011). Aluminum exacerbates brain oxidative damage (Nehru et al, 2007), causes inflammation and induces Ab deposition.…”

Progressive inflammatory pathology in the retina of aluminum-fed 5xFAD transgenic mice

“…Several laboratories have independently studied the effects of supplementing the diets of amyloid-overexpressing Tg-AD murine models (Tg-2576, APP/PS1, 5xFAD, etc.,) with aluminum (as chloride, lactate, maltolate or sulfate) and have evaluated the impact of ingested aluminum with pathological outcome [9–17]. The general consensus is that the presence of aluminum in the diets of Tg-AD murine models enhances AD-type neuropathology: (1) by up-regulating the abundance of pro-inflammatory microRNAs [3], (2) by progressively exacerbating the incidence of oxidative stress [9–12]; (3) by hastening the appearance of Aβ42 peptides, accelerating Aβ42 oligomerization, amyloidogenesis and senile plaque deposition [11–13]; and (4) by increasing apoptosis in brain cells that temporally correlate to deficits in memory, cognition and spatial learning [14–17], all of which are features characteristic of AD neuropathology [9–17]. In these experiments we studied the evolution of Aβ40 and Aβ42 peptides, and the AD-relevant pro-inflammatory biomarkers cyclooxygenase-2 (COX-2) and C-reactive protein (CRP) in the brain and retina of 5xFAD Tg-AD mice fed aluminum in their diet and age-matched controls.…”

Phytoconstituents Profile of Clitoria Ternatea by Gc-MS and Its Age-Related Anticholinergic Activity Against Aluminum and Restraint Stress

“…In the present investigation, in order to determine the agerelated neurodegeneration induced by both RS exposure and environmental neurotoxicant such as AlM were administered to the experimental animals of young and adult male wistar rats. Al has been reported to be involved in neurodisorders such as Alzheimer's disease 25,26,27 . Young and adult rats that were exposed to RS and AlM resulted in significant reduction of ACh and AChE activities in cerebellum.…”