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

INTRODUCTION
Aluminium and oxidative stress
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The model involving aggravation of oxidative stress is among the most
recognized hypothesis of aluminium neurotoxicity but the precise molecular mechanism
by which it causes oxidative damage into the brain remains uncertain. Actually, a large
number of studies confirmed the existence of a state of oxidative stress in most of the
neurodegenerative disorders in which aluminium is present in relative high quantities.
Numerous publications have detailed an increase in the formation of ROS after
aluminium exposure both in vivo and in vitro (Katyal et al. 1997, Flora et al. 2003,
Ogasawara et al. 2003, Nehru and Anand 2005). However, the reported results as a
whole appear controversial, to such an extent that both pro-oxidant (Zatta et al. 2002,
Exley 2004a) and antioxidant (Oteiza et al. 1993a, Abukadar et al. 2004a) properties
have been attributed to this metal.
The brain: a target for aluminium
The brain is a main target for aluminium neurotoxicity as it is highly susceptible
to oxidative insult for several reasons: (a) a high oxygen turnover as the brain consumes
a proportionally larger amount of oxygen than other organs, around 20% of the body‟s
oxygen (Halliwell 1992), (b) a low mitotic rate, (c) low concentrations/activities of
brain antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), and
glutathione peroxidase (GPx), (d) (Halliwell and Gutteridge 1985) a large amount of
highly oxidizable polyunsaturated fatty acids in neuronal cell membranes (Table 5), and
(e) a high brain content of iron (Youdim 1988).
Several hypotheses have been given to explain the possible link between
aluminium and the promotion of oxidative stress (Exley 2004a). Actually, even though
aluminium is not a transition metal, and consequently does not undergo redox reactions,
it can cause oxidative stress both in vivo and in vitro through multiple mechanisms. As
examples, it has been shown to stimulate in vitro iron-induced and non-iron-induced
lipid peroxidation (Gutteridge et al. 1985, Verstraeten and Oteiza 2000, Meglio and