The promotion of iron-induced generation of reactive oxygen species in nerve tissue by aluminum

Aluminum is suspected to play a role in several neurological disorders. Reactive oxygen species (ROS) lead to oxidative stress, which is thought to be a possible mechanism for neurological damage. Interactions between aluminum and iron, a known promoter of prooxidant events, were studied in cerebral tissues using a fluorescent probe to measure rates of generation of ROS. Al-2(SO4)(3) alone failed to stimulate ROS production over a wide range of concentrations (50-1000 mu M). The aluminum-deferrioxamine chelate in the absence of iron could also not potentiate ROS formation. However, Al-2(SO4)(3) potentiated FeSO4-induced ROS, with a maximal effect at 10 mu M Fe and 500 mu M Al. Kaolin, a hydrated aluminum silicate, did not potentiate iron-induced ROS formation. Ferritin had a minor stimulatory effect on ROS generation, but this was not potentiated by the concurrent presence of Al-2(SO4)(3). Transferrin had no effect on basal rates of ROS generation, but when Al-2(SO4)(3) was also present, ROS production was enhanced. It is concluded that: 1. There is a potentiation of iron-induced ROS by aluminum salts; 2. Free or complexed aluminum alone is not a key producer of ROS; and 3. High rates of ROS production are unlikely to be owing to the displacement by aluminum iron from its biologically sequestered locations.