Aluminum Has Both Oxidant and Antioxidant Effects in Mouse Brain Membranes

The in vitro effects of aluminum (A1) on lipid peroxidation were studied in mouse brain homogenates and purified brain subcellular fractions. In brain homogenates prepared in 5 mM Na₂HPO₄, 0.14 M NaCl, pH 7.4, the addition of Al decreased Fe²⁺-induced lipid peroxidation, measured as 2-thiobarbituric acid- reactive substances (TBARS), in a dose dependent manner, with a maximum effect at 250 μM Al. In brain homogenates prepared in 20 mM Tris-HCI, 0.14 M NaCl, pH 7.4, Al acted as a prooxidant at 250 and 500 μM concentrations. The prooxidant effect of Al was enhanced with increasing concentrations of Fe²⁺. In brain microsonies Al increased TBARS production and conjugated dienes formation, both depending on the addition of Fe²⁺. In myelin, the prooxidant effect of Al on Fe²⁺-induced lipid peroxidation was eliminated when membranes were disrupted with 0.2% Triton X-100. Thus, in brain homogenates, microsomes, and myelin, Al has the potential for exhibiting both prooxidant and antioxidant activity depending on the concentration of Fe²⁺ and Al in the media and on membrane integrity. Similar to Al, Be²⁺ and La³⁺ had prooxidant effects on Fe²⁺-induced lipid peroxidation in myelin, suggesting that membrane damage secondary to induced lipid peroxidation may be a common mechanism underlying tissue pathology even with metals without redox capacity. Oxidative damage to brain cell components may be an important mechanism mediating the neurotoxicity of Al.