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

INTRODUCTION
Oteiza 1999), non-iron-mediated oxidation of NADH (Meglio and Oteiza 1999, Kong et
al. 1992), and non-iron-mediated formation of the � OH (Méndez-Álvarez et al. 2002).
Table 5: Lipid composition of normal adult human brain (dry weight)
(Zatta et al. 2002)
Gray matter (%) White matter (%)
Cholesterol 22 27.5
Total phospholipids 69.5 45.9
Phosphatidylserine 8.7 7.9
Galactocerebroside 5.4 19.8
Galactocerebroside sulphate 1.7 5.4
Aluminium catalyses iron-driven biological oxidations
Aluminium was also shown to potentiate the capacity of pro-oxidants transition
metals, such as iron and copper which are present in most cell compartments, to
produce oxidative stress (Bondy and Kirstein 1996, Bondy et al. 1998). It was
hypothesized that colloidal aluminium may complex these pro-oxidant metals and
permit them to participate in Fenton reaction for an extended time (Yang et al. 1999,
Campbell et al. 2001).
Aluminium stimulates superoxide-/non-iron-driven biological oxidations
We have seen that O2 ●─ is the ROS with the lowest oxidant capacity but it can
undergo a one-electron transfer to generate H2O2 which can in turn through the Fenton
reaction and in the presence of reduced metal ions, be converted to ● OH, increasing its
redox potential. Various studies proposed that aluminium could enhance the O2 ●─ -
mediated oxidation in different systems that generate this ROS: the photochemical
decomposition of rose Bengal (Kong et al. 1992, Meglio and Oteiza 1999), the
autoxidation of 6-OHDA (Méndez-Álvarez et al. 2002), the vanadium-mediated
oxidation of NADH (Adler et al. 1995), and the xanthine/xanthine oxidase system
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