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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INTRODUCTION<br />
Coble 1987). Transdermal absorption <strong>of</strong> only 0.012% has been reported after a one-time<br />
underarm application <strong>of</strong> 26 Al chlorhydrate (Flarend et al. 2001) while a case report<br />
showed that transdermal uptake <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> may also be important (Guillard et al.<br />
2004).<br />
Distribution <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> <strong>in</strong> the body<br />
60<br />
Once absorbed <strong>in</strong>to the bloodstream, <strong>alum<strong>in</strong>ium</strong> circulates bound to various<br />
plasma prote<strong>in</strong>s: 93% is bound to transferr<strong>in</strong>, 6% to citrate and the rema<strong>in</strong><strong>in</strong>g to<br />
hydroxide and phosphate (Harris et al. 2003). The metal is distributed unequally to all<br />
tissues with<strong>in</strong> the body throughout normal and <strong>alum<strong>in</strong>ium</strong>-<strong>in</strong>toxicated <strong>in</strong>dividuals<br />
(Alfrey et al. 1980, Di Paolo et al. 1997), and <strong>alum<strong>in</strong>ium</strong>-treated experimental animals<br />
(Greger and Sutherland 1997). The highest levels <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> <strong>in</strong> mammalian tissues<br />
are found <strong>in</strong> the skeleton and lungs, approximately 50% and 25% <strong>of</strong> the 30 to 50 mg<br />
<strong>alum<strong>in</strong>ium</strong> body burden <strong>in</strong> the healthy human subject (Alfrey 1984, Ganrot 1986,<br />
ATSDR 1999). Alum<strong>in</strong>ium also accumulates <strong>in</strong> human bra<strong>in</strong>, sk<strong>in</strong>, lower<br />
gastro<strong>in</strong>test<strong>in</strong>al tract, lymph nodes, adrenals, and parathyroid glands (Tipton and Cook<br />
1963, Hamilton et al. 1973, Cann et al. 1979, Alfrey 1980).<br />
Alum<strong>in</strong>ium accumulation <strong>in</strong> different target organs varies with the <strong>alum<strong>in</strong>ium</strong><br />
salt adm<strong>in</strong>istered, species studied and route used, dose and duration <strong>of</strong> exposure (D<strong>in</strong>g<br />
and Zhu 1997, Yokel and McNamara 1988), but also with age, kidney function, disease<br />
status, and dietary compounds (Greger 1993). The human bra<strong>in</strong> conta<strong>in</strong>s lower levels <strong>of</strong><br />
<strong>alum<strong>in</strong>ium</strong> when compared to other organs (Walker et al. 1994, Andrási et al. 2005,<br />
Yokel and McNamara 2001). In the case <strong>of</strong> dialysis encephalopathy, this concentration<br />
may aument drastically (Alfrey et al. 1976).