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

INTRODUCTION
Oxidative damage happens in all our tissues all the time. There is a basal level of
oxidative damage to DNA, lipids and proteins (Halliwell and Gutteridge 2006) and
under normal conditions free radicals will be quickly detoxified by the body‟s defence
systems. Mechanisms that resist against oxidative damage comprise antioxidant
scavengers such as glutathione (GSH), ascorbic acid (AA), alfa-tocopherol, carotenoids,
flavonoids, polyphenols and antioxidant enzymes. These latter, SOD, GPx, CAT, are
known to be responsible for the detoxification of ROS: SOD catalysing the dismutation
of two molecules of O2 ●� to give H2O2 and O2, and GPx and CAT participating in the
removal of H2O2 (Reactions 2 and 3). Nevertheless, under certain circumstances, greater
amounts of ROS and RNS are produced, which finish up by overcoming the cellular
defence mechanisms. Failures in the systems that repair and replace oxidized
biomolecules contribute to a situation of oxidative stress, defined as “an imbalance
between oxidants and antioxidants, in favour of the oxidants, leading to a disruption of
redox signaling and control and/or molecular damage” (Sies and Jones 2007).
Reaction 2: Dismutation of O2 by SOD
●─ +
2 O2 + 2H H2O2 + O2
Reaction 3: Removal of H2O2 by GPx
2 GSH + H2O2
SOD
GPx
GSSG + 2H2O
In the past decades, oxidative stress was the first common pathogenic factor to
be considered as contributing to the degeneration of DAergic neurons in PD (Jenner
1998, Lang and Lozano 1998, Schapira 1999). Increased SOD, iron, lipid peroxidation
markers and nitrated proteins levels, and decreased GSH levels in SNpc of PD patients
suggested that oxidative stress may play a significant function in PD neurodegeneration
(Saggu et al. 1989, Sofic et al. 1991, Sofic et al. 1992, Ilic et al. 1999, Agil et al. 2006).
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