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. 2014 Mar 11:10:6.
doi: 10.1186/1744-9081-10-6.

Hippocampal neuronal metal ion imbalance related oxidative stress in a rat model of chronic aluminum exposure and neuroprotection of meloxicam

Affiliations

Hippocampal neuronal metal ion imbalance related oxidative stress in a rat model of chronic aluminum exposure and neuroprotection of meloxicam

Lijuan Yu et al. Behav Brain Funct. .

Abstract

Neurodegenerative diseases remain a significant unresolved societal burden afflicting millions of people worldwide. Neurons in the brain are highly sensitive to oxidative stress, which can be induced by metal toxicity. In this paper, a chronic aluminum overload-induced model of neurodegeneration was used to investigate whether metal ions (Al, Fe, Mn, Cu and Zn)-related oxidative stress was involved in neurodegenerative mechanism and to identify the protective action of meloxicam against rat hippocampal neuronal injury. The metal ion contents, activity of superoxide dismutase (SOD), and content of malondialdehyde (MDA) were detected. The results showed that the spatial learning and memory (SLM) function was significantly impaired in chronic aluminum overload rats. Considerable karyopycnosis was observed in hippocampal neurons. The SOD activity was weakened and the MDA content increased both significantly. In the hippocampus, Al, Fe, Mn, Cu, and Zn contents increased by 184.1%, 186.1%, 884.2%, 199.4% and 149.2%, respectively. Meloxicam administration (without Al) had no effect compared with the control group, while meloxicam treatment with aluminum exposure significantly protected rats from SLM function impairment, neuron death, lower SOD activity, higher MDA content and brain metal ion imbalance. Our findings suggest that the cerebral metal ion imbalance-related oxidative stress is involved in mechanism of cerebral injury and neurodegeneration induced by chronic Al overload in rats, and that meloxicam protects neurons by reducing metal ion imbalance-related oxidative stress.

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Figures

Figure 1
Figure 1
Changes of neuronal pathomorphology in chronic aluminum overload rat hippocampus. a. Neuronal pathomorphology in chronic aluminum overload rat hippocampus (HE × 400). A: Control group; B: Meloxicam 3 mg kg−1 group; C: Meloxicam 1 mg kg−1 group; D: Model group; E: Al + Meloxicam 3 mg kg−1 group; F: Al + Meloxicam 1 mg kg−1 group. b. Group data showing the effect of meloxicam on the cell death rate. ##P < 0.01, vs. control group; **P < 0.01, vs. model group; aaP < 0.01, vs. Al + M-1 group; Al + M-3 group: Al + meloxicam 3 mg kg−1 group; Al + M-1 group: Al + meloxicam 1 mg kg−1 group (mean ± SD, n = 3).
Figure 2
Figure 2
Changes of aluminum content of chronic aluminum overload rat hippocampus (mean ± SD, n = 3). ##P < 0.01, vs. control group; *P < 0.05, vs. model group; aP < 0.05, vs. Al + M-1 group; M-3 group: meloxicam 3 mg · kg−1 group; M-1 group: meloxicam 1 mg · kg−1 group; Al + M-3 group: Al + meloxicam 3 mg · kg−1 group; Al + M-1 group: Al + meloxicam 1 mg · kg−1 group. μg/g: μg per g of wet weight tissue.
Figure 3
Figure 3
Changes of iron content of chronic aluminum overload rat hippocampus (mean ± SD, n = 3). ##P < 0.01, vs. control group; *P < 0.05, vs. model group; aP < 0.05, vs. Al + M-1 group; M-3 group: meloxicam 3 mg · kg−1 group; M-1 group: meloxicam 1 mg · kg−1 group; Al + M-3 group: Al + meloxicam 3 mg · kg−1 group; Al + M-1 group: Al + meloxicam 1 mg · kg−1 group. μg/g: μg per g of wet weight tissue.
Figure 4
Figure 4
Changes of manganese content of chronic aluminum overload rat hippocampus (mean ± SD, n = 3). ##P < 0.01, vs. control group; **P < 0.01, vs. model group; M-3 group: meloxicam 3 mg · kg−1 group; M-1 group: meloxicam 1 mg · kg−1 group; Al + M-3 group: Al + meloxicam 3 mg · kg−1 group; Al + M-1 group: Al + meloxicam 1 mg · kg−1 group. μg/g: μg per g of wet weight tissue.
Figure 5
Figure 5
Changes of copper content of chronic aluminum overload rat hippocampus (mean ± SD,n = 3). ##P < 0.01, vs. control group; *P < 0.05, **P < 0.01, vs. model group; M-3 group: meloxicam 3 mg · kg−1 group; M-1 group: meloxicam 1 mg · kg−1 group; Al + M-3 group: Al + meloxicam 3 mg · kg−1 group; Al + M-1 group: Al + meloxicam 1 mg · kg−1 group. μg/g: μg per g of wet weight tissue.
Figure 6
Figure 6
Changes of zinc content of chronic aluminum overload rat hippocampus (mean ± SD, n = 3). ##P < 0.01, vs. control group; *P < 0.05, **P < 0.01, vs. model group; aP < 0.05, vs. Al + M-1 group; M-3 group: meloxicam 3 mg · kg−1 group; M-1 group: meloxicam 1 mg · kg−1 group; Al + M-3 group: Al + meloxicam 3 mg · kg−1 group; Al + M-1 group: Al + meloxicam 1 mg · kg−1 group. μg/g: μg per g of wet weight tissue.

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