Implications for atypical antioxidative properties of manganese in iron-induced brain lipid peroxidation and copper-dependent low density lipoproteinconjugation

Our group recently observed that manganese prevents oxidative brain injury in the iron-induced parkinsonian animal model. It has also been suggested t hat manganese retards while copper promotes the development of atherosclero sis. In this report, we provide further evidence to support a controversial notion that manganese is an atypical antioxidant. Among transition metals, Cu2+ and Fe2+ (0.1 to 125 mu M) but not Mn2+, converted hydrogen peroxide to reactive hydroxyl radicals via the Fenton reaction at pH 7.4. Iron's pro -oxidative rate is relatively slow, but it is accelerated further by ascorb ate (50 mu M) in 37 degrees C Dulbecco's phosphate buffered saline. Moreove r, Mn2+ (0-80 mu M) concentration dependently retarded diene conjugation of human low density lipoproteins stimulated by 5 mu M Cu2+. This new result is consistent with our recent finding that Mn2+ (0 to 20 mu M) does not ini tiate bra in lipid peroxidation while it inhibits iron-induced peroxidation of polyunsaturated fatty acids. These unexpected manganese results are som ewhat at odds with a prominent theory that manganese is a prooxidative tran sition metal. Furthermore, iron and copper induced free radical generation and lipid peroxidation are suppressed by lowering the incubation temperatur e; this suggests that hypothermia may decrease the oxidative stress and dam age in vivo. In conclusion, normal dietary intake of manganese may protect cells and neurons from oxidant stress through the inhibition of propagation of lipid peroxidation caused by hydroxyl radicals generated by prooxidativ e transition metals such as iron and copper. Potential therapeutical uses o f manganese, manganese SOD mimetics and hypothermia for protecting brain ne urons and vascular endothelial cells aga inst oxidative stress and damage h ave been successfully demonstrated in both animal models and clinical trial s. (C) 1999 Inter Press, Inc.