Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...

SUMMARY
values were attained at 48 hours post-injection for both TBARS and PCC, and at 24
hours for PTC. Interestingly, lower but significant increases in oxidative stress levels
were also seen in the contralateral side (ventral midbrain and striatum) excluding this
zone as a control to determine neurochemical alterations caused by 6-OHDA in this
experimental model of PD. At last and according to the obtained results, we decided to
establish the optimal time of 48 hours post-injection for quantification of brain
oxidative stress indices when assessing the oxidative potential of aluminium in this
experimental model of PD.
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The second part of this thesis consisted in developing a dosage regimen of
aluminium to rats which would guarantee a significant accumulation of this metal in
brain areas and also to determine its precise distribution in the brain. As it was
previously suggested that aluminium distribution depends on the animal species in
question and the chemical form of aluminium administered, we opted for two distinct
administration routes: oral and intraperitoneal. Sprague-Dawley rats were either daily
i.p. injected with aluminium chloride (10 mg Al 3+ /kg/day) for 1 week, or given orally
progressive increasing doses of aluminium chloride (25, 50, 100 mg Al 3+ /kg/day)
supplemented with citrate (89, 178, 356 mg/kg/day) during 4 weeks. Our results showed
that both administration routes led to aluminium accumulation. A greater and more
significant increase was noted in the group receiving aluminium via intraperitoneal
administration for most brain areas except in ventral midbrain. Distribution also varied
with the administration route used. In accordance to these results we resolved to use the
intraperitoneal administration route to clarify the brain oxidative stress provoked by
aluminium.
Finally the third phase of this thesis was dedicated to determine the ability of
aluminium to alter the oxidant status of specific brain areas, such as cerebellum, ventral
midbrain, cortex, hippocampus, and striatum. Male Sprague-Dawley rats were
intraperitoneally administered with aluminium chloride (10 mg Al 3+ /kg/day) in saline
for 10 days. As we demonstrated before, this dosage procedure was sufficient to insure
aluminium accumulation in brain areas. Animals were sacrificed 48 hours after lesion to
perform lipid peroxidation and protein oxidation studies because the peak for oxidative