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 2 significant increase of the metal concentration in the ventral midbrain, i.p. administration led to a decrease in aluminium concentration in this cerebral region. In our opinion, this curious observation could be related to the specific composition of this area and the reported ability of aluminium to change the permeability of plasma membranes in function of their particular composition (Silva et al. 2002). 112 Our results clearly show that aluminium accumulation in the brain not only varied with the administration route used but also in its distribution in the distinct brain areas. Evidently, both the presence of citric acid in the oral dose of aluminium and the difference in the time of treatment also could contribute to the reported differences. However, in view of the reported variance in aluminium distribution in different cerebral regions following both treatments, it can be argued that the effects of aluminium cannot be generalized to the whole brain and a study of the kinetics of aluminium distribution in specific cerebral areas is necessary to understand the neurotoxicity of this metal and its contribution to a particular neurological disorder. Acknowledgments This study was supported by the Xunta de Galicia (Santiago, Spain; Grant PGIDIT03PXIB20804PR).

Table 1. Graphite furnace programme for aluminium determination by ETAAS Step Temperature (ºC) Ramp (s) Hold (s) Ar flow (mL min -1 ) Dry 150 15 20 300 Pyrolisis 1500 15 20 300 Atomization 2800 0 5 50 (read) Cleaning 2200 1 5 300 CHAPTER 2 Fig. 1 Levels of aluminium in the different areas of the rat brain. Data are expressed as mean ± SD. Asterisks denote values significantly different (one-way ANOVA followed by a Bonferroni‟s test) for treatment versus control group (*, p < 0.01, **, p < 0.001) and for the oral-treated group versus intraperitoneally-treated group (***, p < 0.001). �g Al 3+ / g 20 15 10 5 0 Control Al-treated ** *** * * *** ** ** i.p. oral i.p. oral i.p. oral i.p. oral i.p. oral CE VM CO H ST ** *** ** *** * ** *** ** 113

CHAPTER 2<br />

significant <strong>in</strong>crease <strong>of</strong> the metal concentration <strong>in</strong> the ventral midbra<strong>in</strong>, i.p.<br />

adm<strong>in</strong>istration led to a decrease <strong>in</strong> <strong>alum<strong>in</strong>ium</strong> concentration <strong>in</strong> this cerebral region. In<br />

our op<strong>in</strong>ion, this curious observation could be related to the specific composition <strong>of</strong> this<br />

area and the reported ability <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> to change the permeability <strong>of</strong> plasma<br />

membranes <strong>in</strong> function <strong>of</strong> their particular composition (Silva et al. 2002).<br />

112<br />

Our results clearly show that <strong>alum<strong>in</strong>ium</strong> accumulation <strong>in</strong> the bra<strong>in</strong> not only<br />

varied with the adm<strong>in</strong>istration route used but also <strong>in</strong> its distribution <strong>in</strong> the dist<strong>in</strong>ct bra<strong>in</strong><br />

areas. Evidently, both the presence <strong>of</strong> citric acid <strong>in</strong> the oral dose <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> and the<br />

difference <strong>in</strong> the time <strong>of</strong> treatment also could contribute to the reported differences.<br />

However, <strong>in</strong> view <strong>of</strong> the reported variance <strong>in</strong> <strong>alum<strong>in</strong>ium</strong> distribution <strong>in</strong> different<br />

cerebral regions follow<strong>in</strong>g both treatments, it can be argued that the effects <strong>of</strong><br />

<strong>alum<strong>in</strong>ium</strong> cannot be generalized to the whole bra<strong>in</strong> and a study <strong>of</strong> the k<strong>in</strong>etics <strong>of</strong><br />

<strong>alum<strong>in</strong>ium</strong> distribution <strong>in</strong> specific cerebral areas is necessary to understand the<br />

<strong>neurotoxicity</strong> <strong>of</strong> this metal and its contribution to a particular neurological disorder.<br />

Acknowledgments<br />

This study was supported by the Xunta de Galicia (Santiago, Spa<strong>in</strong>; Grant<br />

PGIDIT03PXIB20804PR).

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