title: Aluminum has both oxidant and antioxidant effects in mouse brain membranes.
abstract: 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.
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: P I
authors.initials: PI
authors.lastname: Oteiza
authors.forename: C G
authors.initials: CG
authors.lastname: Fraga
authors.forename: C L
authors.initials: CL
authors.lastname: Keen
mesh_terms: 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
chemical_list: D000975:Antioxidants; D002413:Cations, Divalent; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D000535:Aluminum; D007501:Iron