Aluminum has both oxidant and antioxidant effects in mouse brain membranes.
The in vitro effects of aluminum (Al) 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 Fe(2+)-induced lipid peroxidation, measured as 2-thiobarbituric acid-reactive substances (TBARS), in a dose dependent manner, with a maximum effect at 250 microM Al. In brain homogenates prepared in 20 mM Tris-HCl, 0.14 M NaCl, pH 7.4, Al acted as a prooxidant at 250 and 500 microM concentrations. The prooxidant effect of Al was enhanced with increasing concentrations of Fe2+. In brain microsomes Al increased TBARS production and conjugated dienes formation, both depending on the addition of Fe2+. In myelin, the prooxidant effect of Al on Fe(2+)-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 Fe(2+)-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.
Oteiza
P I
PI
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Fraga
C G
CG
Keen
C L
CL
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000975:Antioxidants; D002413:Cations, Divalent; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D000535:Aluminum; D007501:Iron