Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...
Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...
Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...
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CHAPTER 3<br />
difference <strong>in</strong> the levels <strong>of</strong> both lipid peroxidation and prote<strong>in</strong> oxidation for PCC.<br />
Although, these results are <strong>in</strong> partial agreement with the results obta<strong>in</strong>ed with non-<br />
lesioned rats, they do not agree with the <strong>in</strong> vitro results obta<strong>in</strong>ed us<strong>in</strong>g bra<strong>in</strong><br />
mitochondria preparations, <strong>in</strong> which we found no significant effect due to the presence<br />
<strong>of</strong> <strong>alum<strong>in</strong>ium</strong>. Evidently, these f<strong>in</strong>d<strong>in</strong>gs corroborate the importance <strong>of</strong> the <strong>in</strong> vivo<br />
studies <strong>in</strong> this k<strong>in</strong>d <strong>of</strong> <strong>in</strong>vestigation, which appears to be a consequence <strong>of</strong> the tight<br />
relationship exist<strong>in</strong>g among the different molecular mechanisms coexist<strong>in</strong>g with<strong>in</strong> the<br />
bra<strong>in</strong>. Our immunochemical study showed that <strong>alum<strong>in</strong>ium</strong> adm<strong>in</strong>istration alone caused<br />
no significant change <strong>in</strong> TH-ir striatal term<strong>in</strong>als. In contrast, lesion with 6-OHDA<br />
caused a loss <strong>of</strong> TH-ir striatal term<strong>in</strong>als, which was significantly <strong>in</strong>creased with the<br />
adm<strong>in</strong>istration <strong>of</strong> <strong>alum<strong>in</strong>ium</strong>. Obviously, these data show the ability <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> to<br />
<strong>in</strong>crease the capacity <strong>of</strong> 6-OHDA to cause nigrostriatal neurodegeneration. Evidently,<br />
the importance <strong>of</strong> these data is <strong>in</strong>creased by the ability <strong>of</strong> neuromelan<strong>in</strong> to b<strong>in</strong>d<br />
<strong>alum<strong>in</strong>ium</strong> which may be the cause <strong>of</strong> the high concentration <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> found <strong>in</strong> the<br />
bra<strong>in</strong> <strong>of</strong> certa<strong>in</strong> patients suffer<strong>in</strong>g PD (Yasui et al. 1992). Furthermore, our results also<br />
help us understand the reported ability <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> to potentiate etiological agents and<br />
accelerate the progression <strong>of</strong> a disease (Exley and Esiri 2006). In conclusion, <strong>alum<strong>in</strong>ium</strong><br />
acts ma<strong>in</strong>ly as a pro-oxidant probably by reduc<strong>in</strong>g the activity <strong>of</strong> defence antioxidant<br />
enzymes. In addition, the <strong>in</strong>crease <strong>in</strong> <strong>oxidative</strong> <strong>stress</strong> together with enhanced 6-OHDA-<br />
<strong>in</strong>duced neurodegeneration, suggest the participation <strong>of</strong> free radical-<strong>in</strong>duced <strong>oxidative</strong><br />
cell <strong>in</strong>jury <strong>in</strong> mediat<strong>in</strong>g <strong>alum<strong>in</strong>ium</strong> <strong>neurotoxicity</strong>. Interest<strong>in</strong>gly, we demonstrated that<br />
<strong>alum<strong>in</strong>ium</strong> neither enhanced lipid peroxidation nor decreased antioxidant enzyme<br />
activities <strong>in</strong> the hippocampus. Given that <strong>alum<strong>in</strong>ium</strong> content was markedly <strong>in</strong>creased <strong>in</strong><br />
the hippocampus (Sánchez-Iglesias et al. 2007b), this dual effect could be related to the<br />
biphasic behaviour <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> previously reported by Abubakar et al. (2004a). In our<br />
op<strong>in</strong>ion, the high concentration <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> <strong>in</strong> the hippocampus may possibly <strong>in</strong>duce<br />
an <strong>in</strong>crease <strong>in</strong> defence enzyme levels, which could cause the steady state <strong>of</strong> TBARS<br />
levels after <strong>alum<strong>in</strong>ium</strong> exposure. However, <strong>in</strong> the rema<strong>in</strong><strong>in</strong>g cerebral areas, antioxidant<br />
enzymes have a lower activity, which is <strong>in</strong>terpreted as a consequence <strong>of</strong> the postulated<br />
oxidant potential <strong>of</strong> AlO2 ●2+ (Kong et al. 1992, Exley 2004a) and consequently the<br />
factor responsible for the <strong>oxidative</strong> impairment found <strong>in</strong> those bra<strong>in</strong> areas. F<strong>in</strong>ally, we<br />
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