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.
ASJC Scopus subject areas
- Molecular Biology