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Title: Effects of aluminium on cells of the brain and liver : modification by selenium and vitamin E
Author: Abubakar, Mu'azu Gusau
ISNI:       0000 0001 3392 6430
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2002
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It has been hypothesised that aluminium (A1) toxicity is mediated at least in part by free radicals. The in vitro potential of aluminium to induce pro-oxidant (or antioxidant effects) was studied in rat primary cortical astrocytes and human neuroblastoma cells (SHSY-5Y). The cells were exposed to aluminium sulphate. This had a differential effect dependent on cell type. Human neuroblastoma cells (SHSY-5Y) were more susceptible to the toxic effects of aluminium sulphate exposure than cortical astrocytes (primary astrocytes). The toxic effects were assessed using mitochondrial dehydrogenase activity, using the MTT assay and propidium iodide staining. Cell redox status was assessed by glutathione content, malondialdehyde production and superoxide dismutase activity. In vivo markers of oxidative stress were determined in liver and brain of rats exposed to aluminium lactate, either alone, or in the presence of dietary supplements of selenium (as selenite) or vitamin E as a-tocopherol. Selenium supplements for twenty one days resulted in a statistically significant decrease in brain glutathione in the groups treated with aluminium (P < 0. 05). There was no significant effect on hepatic glutathione in animals supplemented with either Se or Al, but Al in combination with Se prevented this elevation. In the brain a statistically significant decrease (P < 0. 001) in the GSH content was observed. Contrary to what has been reported, Al exposure resulted in statistically significant decrease (P < 0. 001) in lipid peroxidation as measured by production of malondialdehyde in both liver and brain. Aluminium exposure had no significant effect on the liver and brain superoxide dismutase activity. Results of the present study suggest that in the rat, aluminium exposure may have both pro-oxidant and antioxidant effect and Se supplementation may modulate these effects. Aluminium was administered to Wistar rats as intraperitoneal injection of aluminium lactate (10 mg Al/Kg body weight) 5 times a week for 4 weeks. Rats were either treated with aluminium alone, or additionally received vitamin E as a dietary supplement of 5, 15, and 20 mg/g, of food. Further control groups received a diet containing 20 mg/g vitamin E or normal chow without added aluminium. The aluminium content of plasma and liver was significantly increased (P < 0. 001) in all groups receiving i. p. aluminium. Hepatic reactive oxygen species (ROS) were significantly higher (P < 0. 01) in the aluminium treated groups and this was attenuated (P0. 05) in the animals receiving concomittant vitamin E. The aluminium-induced changes in ROS were associated with a significant reduction (P < 0. 05) in the hepatic reduced glutathione and catalase activity. Hence i. p. aluminium appears to induce oxidative stress in the liver. The regional accumulation of aluminium (Al) in the brain was investigated. Rat brains were dissected into identifiable regional segments, namely cortex, cerebellum, medulla, hippocampus, striatum and hypothalamus, for measurement of Al by atomic absorption spectrometry. Al content was increased in all the regions of the brain examined, in the Al-treated rats compared to the controls (p cortex > hippocampus > medulla > striatum. Concomitant dietary vitamin E significantly reduced (P < 0. 01) the Al accumulation in various regions of the brain. These results suggest that dietary vitamin E may influence the regional accumulation of Al in the brain. Hence if Al-induced neurotoxicity is mediated by pro-oxidant events, vitamin E may offer some protection. Raman microspectroscopy of paraffin-embedded tissue sections was used to investigate the effect of aluminium exposure on brain section. Despite the complexity of the system, differential Raman spectral characteristic between the Al-treated and untreated brain tissue samples were shown. These are attributed to changes in the packing and conformation of protein material. Much work remains to be done to optimise experimental conditions and to quantify the effect, nevertheless, the results reported here demonstrate the benefits of these Raman microspectroscopic studies with such complex biosamples.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available