Oteiza P I, Fraga C G, Keen C L
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Arch Biochem Biophys. 1993 Jan;300(1):517-21. doi: 10.1006/abbi.1993.1070.
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.
研究了铝（Al）对小鼠脑匀浆和纯化脑亚细胞组分脂质过氧化的体外作用。在pH 7.4的5 mM Na2HPO4、0.14 M NaCl中制备的脑匀浆中，添加Al以剂量依赖性方式降低了Fe(2+)诱导的脂质过氧化，以2-硫代巴比妥酸反应性物质（TBARS）衡量，在250 microM Al时效果最佳。在pH 7.4的20 mM Tris-HCl、0.14 M NaCl中制备的脑匀浆中，Al在250和500 microM浓度下作为促氧化剂。Al的促氧化作用随着Fe2+浓度的增加而增强。在脑微粒体中，Al增加了TBARS的产生和共轭二烯的形成，两者均依赖于Fe2+的添加。在髓磷脂中，当用0.2% Triton X-100破坏膜时，Al对Fe(2+)诱导的脂质过氧化的促氧化作用被消除。因此，在脑匀浆、微粒体和髓磷脂中，Al有可能根据培养基中Fe2+和Al的浓度以及膜的完整性表现出促氧化和抗氧化活性。与Al类似，Be2+和La3+对髓磷脂中Fe(2+)诱导的脂质过氧化具有促氧化作用，表明即使对于没有氧化还原能力的金属，诱导脂质过氧化继发的膜损伤可能是组织病理学的共同机制。对脑细胞成分的氧化损伤可能是介导Al神经毒性的重要机制。
