Alpha-Tocopherol Supplementation Restricts Aluminium- and Ethanol-Induced Oxidative Damage in Rat Brain but Fails to Protect Against Neurobehavioral Damage.

The concurrent presence of oxidative stress (OS) and aluminium exposure is an inducer of neurodegenerative changes. Aluminium can augment OS in a pro-oxidant dominant condition. Antioxidative property of α-tocopherol may be useful in restricting these degenerative changes in the brain. OS parameters are tested in frontal cortex (FC), hippocampus (HC), and cerebellum (CL) of α-tocopherol-supplemented (5 IU/day) male Wistar rats exposed to aluminium (10 mg Al/Kg/day; "Al"), ethanol (0.6 g ethanol/Kg/day; "Et"), and both ("Al-Et") and vehicle-treated control ("C") for 4 weeks. The α-tocopherol supplementation restricted regional alterations of reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. Accordingly, the regional superoxide and peroxide handling capacities (SPHC) also remain unaltered. Al-Et group demonstrated significant elevation in the lipid peroxidation level in FC and CL regions compared to the group C; similar elevations in lipid peroxidation were noted in all the tested brain regions of Al group. Likewise, declines in glutathione reductase activity were noted in HC (versus Et group) and CL (versus Al and Et groups) of Al-Et group. Interestingly, changes in behavioral patterns of all the treatment groups are comparable while differing from that of the control group. Significant difference with group C is observed during first through fourth weeks, third to fourth weeks, and second to third weeks in terms of spontaneous motor activity, Rota Rod performance, and Hebb-Williams maze performance, respectively. Hence, the current dose and duration of α-tocopherol supplementation failed to provide full protection against the aluminium-induced neurodegeneration; nevertheless, it could provide only partial protection toward aluminium-induced augmentation of OS in specific brain regions.

Augmentation of aluminum-induced oxidative stress in rat cerebrum by presence of pro-oxidant (graded doses of ethanol) exposure.

Both aluminum and ethanol are pro-oxidants and neurotoxic. Considering the possibilities of co-exposure and sharing mechanisms of producing neurotoxicity, the present study was planned to identify the level of aluminum-induced oxidative stress in altered pro-oxidant (ethanol exposure) status of cerebrum. Male rats were coexposed to aluminum and ethanol for 4 weeks. After the exposure period, cerebral levels of protein, reduced glutathione (GSH), lipid peroxidation (TBARS) were measured. Activities of catalase, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione perioxidase (GPx) of cerebrum were estimated. In most of the cases significant correlations were observed between the alterations and graded ethanol doses, suggesting a dose-dependency in pushing the oxidant equilibrium toward pro-oxidants. Aluminum is found to influence significantly all the studied parameters of oxidative stress. Likewise, ethanol also influenced these parameters significantly, except GR, while the interaction between ethanol and aluminum could significantly influence only the GSH content and GR activity of cerebrum. Present study demonstrate that coexposure of aluminum with pro-oxidant might favor development of aluminum-induced oxidative stress in cerebrum. This observation might be helpful in understanding of mechanism of neurodegenerative disorders and ameliorate them.