Prolonged exposure to excessive aluminium (Al) concentrations is involved in the ethiopathology of certain dementias and neurological disorders. Melatonin is a well-known antioxidant that efficiently reduces lipid peroxidation due to oxidative stress. Herein, we investigated in synaptosomal membranes the effect of melatonin in preventing Al promotion of lipid and protein oxidation when the metal was combined with FeCl3 and ascorbic acid. Lipid peroxidation was estimated by quantifying malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations in the membrane suspension and protein carbonyls were measured in the synaptosomes as an index of oxidative damage. Under our experimental conditions, the addition of A] (0.0001-1mmol/L) enhanced MDA+4-HDA formation in the synaptosomes. In addition, Al (1 mmol/L) raised protein carbonyl contents. Melatonin reduced, in a concentration-dependent manner, lipid and protein oxidation due to Al, FeCl3 and ascorbic acid in the synaptosomal membranes. These results show that melatonin confers protection against Al-induced oxidative damage in synaptosomes and suggest that this indoleamine may be considered as a neuroprotective agent in Al toxicity because of its antioxidant activity. (c) 2007 Elsevier GmbH. All rights reserved.