Zinc and ascorbic acid coordinately promote lipid peroxidation in brain membranes

Zn2+ is present at high concentrations in mammalian brain, and is released in chelatable form after excitation of certain glutamatergic neurons. Recen t observations suggest that it may play an important role in excitotoxic-in duced neural injury. Ascorbic acid has been widely studied as a stimulator or an inhibitor of lipid-peroxide formation, depending on concentration, an d lipid peroxidation has been postulated to be involved in both acute and c hronic neurogenerative diseases. We find that ascorbic acid and Zn2+, at co ncentrations that are achieved in the brain after prolonged synaptic depola rization, coordinately promote lipid-peroxide formation and cause dysfuncti on of membrane-bound proteins. This effect is unique to Zn2+, and other div alent cations do not share a similar synergism with ascorbate. We propose t hat the Zn2+-ascorbate interaction may be an overlooked mechanism of lipid- peroxide formation in brain injury.