Neuroscience, 2010 Nov 26
Aluminium has been proposed as an environmental factor that may affect several enzymes and other biomolecules related to neurotoxicity and Alzheimer's disease (AD). The promising protective effect of aqueous saffron extract and honey syrup on neurotoxicity induced by aluminuim chloride (AlCl(3)) may be derived from their own antioxidant properties.
Balb/c and C57BL/6 mice (35-40g) were injected with AlCl(3), 40 mg/kg/day for 45 days. Each mice strain was divided into four groups: AlCl(3) treated group, AlCl(3) plus water saffron extract group (administered with saffron extract at 200mg/kg b.w. once a day for the experimental period), AlCl(3) plus honey syrup group (administered with honey syrup at 500 mg/kg b.w. for 45 days). The control group received no treatment.
Oxidative stress and antioxidant status were estimated in the brain and differential display was performed for both mice strains to scan the mRNA in the treated and non treated groups. In addition, the up and down regulated genes were isolated, cloned and sequenced. The sequence analysis was performed and compared with the other genes cited on GenBank.
The results show that there was a decrease in the activity of the antioxidant enzymes (p≤ 0.001) such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the AlCl(3) groups of both mice strains. The level of brain thiobarbituric acid reactive substances (TBARS) showed a significant increase (p≤ 0.001) of lipid peroxidation (LPO) in the AlCl(3) groups. There was an indication of carcinogenicity in the AlCl(3) treated group representing an increase in serum tumor markers such as arginase and a-l-fucosidase.
More than 350 band patterns were obtained and about 22 different up-down regulated genes were observed. The sequence analysis of the three selected up-regulated genes revealed that they are similar to BCL-2, R-spondin and the Inositol Polyphosphate 4-Phosphatase genes, respectively. The R-spondin gene was up-regulated in all examined animals except the control ones but the other two genes were only induced in the animals treated with AlCl(3) & honey syrup.
We conclude that the biochemical and molecular studies showed the neurotoxicity of AlCl(3) in the brains of mice. In addition, there was an ameliorative change with saffron extract and honey syrup against AlCl(3) neurotoxicity.
The obtained molecular results suggest that AlCl(3) made induction for BCL-W gene, which is an anticancer gene or belongs to the DNA repair system in the brain cells, as well as for R-spondin and Inositol Polyphosphate 4-Phosphataseas genes, which help in cell proliferation.
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