Hippocampal neuronal metal ion imbalance related oxidative stress in a rat model of chronic aluminum exposure and neuroprotection of meloxicam
1 Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Medical College Rd. No 1, Chongqing Medical University, Chongqing 400016, P. R. China
2 Department of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, P. R. China
Behavioral and Brain Functions 2014, 10:6 doi:10.1186/1744-9081-10-6Published: 11 March 2014
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.