Active oxygen species formation in synaptosomes exposed to an aluminum chelator

This study evaluates the potential of two chelators, 1,2-dimethyl-3-hydroxypyridine-4-one (Hdpp) and 1-n-butyl-2-methyl-3-hydroxypyridin-4-one (Hnbp), to modulate cerebral rates of free radical production. The fluorometric assay for 2',7'-dichlorofluorescein, which is formed by oxidation of a nonfluorescent precursor (2',7'-dichlorofluorescin diacetate), was used to assay reactive oxygen species (ROS) production. The chelator Hdpp alone and the aluminum complexes of each chelator, Al(dpp)(3) and Al(nbp)(3), all inhibited basal rates of generation of ROS within a rat cerebral synaptosomal fraction. In the presence of an iron salt (1 mu M FeSO4), a major enhancement of syn aptosomal ROS formation was apparent. However, with the addition of an equimolar concentration of Hdpp, Al(dpp)(3), or Al(nbp)(3), this stimulation was completely abolished. The N-substituted-3-hydroxy-4-pyridinones have been proposed to be of clinical utility for the removal of iron or aluminum from tissues. The clinical potential of this class of chelator may be enhanced by their ability to inhibit iron-related oxidative events. (C) 1998 Elsevier Science Inc.