Membrane composition can influence the rate of Al³⁺-mediated lipid oxidation: Effect of galactolipids

In the first part of the present study we investigated the effects of pre-natal and early postnatal exposure of mice to high levels of dietary Al³⁺ on myelin lipid composition and lipid oxidation. We found: (1) a significantly higher (104%; P < 0.01) content of brain myelin galactolipids in the high-Al³⁺ group than in controls, and, (2) a significant correlation (r² = 0.70; P < 0.01) between the concentration of myelin galactolipids and TBARS (2-thiobarbituric acid-reactive substances) content, a parameter of lipid oxidation, Based on these results, we evaluated in an in vitro model (liposomes) whether galactolipids could affect the capacity of Al³⁺ to stimulate Fe²⁺-initiated lipid oxidation, and whether this effect could be due to the promotion of changes in membrane physical properties (membrane phase separation and rigidification). The presence of galactolipids (10-40 mol%) in the liposomes caused a concentration-dependent increase in the stimulatory effect of Al³⁺ on Fe²⁺-induced TBARS production, and on the ability of Al³⁺ to induce phase separation and membrane rigidification. The capacity of Al³⁺ (10-100 μM) to induce lateral phase separation in liposomes composed of phosphatidylcholine/phosphatidylserine/galactolipid (36:24:40, molar ratio) was correlated significantly (r² = 0.99; P < 0.001) with the stimulatory action of Al³⁺ on Fe²⁺-induced TBARS production. We propose that the high content of galactolipids found in myelin from Al³⁺-intoxicated mice could favour Al³⁺-induced changes in membrane physical properties, with the subsequent acceleration of lipid oxidation rates.