N-1-acetyl-N-2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant

The biogenic amine N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK) was inv estigated for its potential antioxidative capacity. AFMK is a metabolite ge nerated through either an enzymatic or a chemical reaction pathway from mel atonin. The physiological function of AFMK remains unknown. To our knowledg e, this report is the first to document the potent antioxidant action of th is biogenic amine. Cyclic voltammetry (CV) shows that AFMK donates two elec trons at potentials of 456 mV and 668 mV, and therefore it functions as a r eductive force. This function contrasts with all other physiological antiox idants that donate a single electron only when they neutralize free radical s. AFMK reduced 8-hydroxydeoxyguanosine formation induced by the incubation of DNA with oxidants significantly. Lipid peroxidation resulting from free radical damage to rat liver homogenates was also prevented by the addition of AFMK. The inhibitory effects of AFMK on both DNA and lipid damage appea r to be dose-response related. In cell culture, AFMK efficiently reduced hi ppocampal neuronal death induced by either hydrogen peroxide, glutamate, or amyloid beta (25-35) peptide. AFMK is a naturally occurring molecule with potent free radical scavenging capacity (donating two electrons/molecule) a nd thus may be a valuable new antioxidant for preventing and treating free radical-related disorders.