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. © 1993 Academic Press, Inc.