6-Hydroxymelatonin converts Fe (III) to Fe (II) and reduces iron-induced lipid peroxidation

Disorders of iron accumulation are known to produce hepatotoxicity. Agents, which can reduce Fe(3+) to a more usable form Fe(2+) could potentially limit such damage. Since it has been previously demonstrated that the pineal secretory product, melatonin, is able to bind iron, we decided to investigate the potential protective properties of the principal melatonin metabolite and degradant, 6-hydroxymelatonin (6-OHM). Using adsorptive cathode stripping voltammetry (AdCSV) we showed that Fe(3+) in the presence of 6-OHM is converted to Fe(2+). We further demonstrated that 6-OHM reduces the Fe(2+)-induced rise in lipid peroxidation in rat liver homogenates. The results imply that 6-OHM facilitates the conversion of Fe(3+) to Fe(2+) which is a more biologically usable form of iron. While such a conversion could also potentially make more Fe(2+) available for driving the Fenton reaction and the consequent generation of the dangerous hydroxyl radical, 6-OHM is able to quench these radicals, thereby providing tissue protection.