Reaction of melatonin and related indoles with hydroxyl radicals: EPR and spin trapping investigations.

It has been suggested that the indole hormone melatonin (N-acetyl-5-methoxytryptamine, MLT) is an important natural antioxidant and free radical scavenger [J. Pineal Res., 14:51; 1993]. In the present work we determined the rate constants, k(r), for scavenging .OH radicals by melatonin, 5-methoxytryptamine (5-MeO-T), 5-hydroxytryptamine (serotonin, 5-OH-T), 6-chloromelatonin (6-Cl-MLT), 6-hydroxymelatonin (6-OH-MLT), and kynurenine (KN) in aqueous solutions. Hydroxyl radicals were generated using a Fenton reaction in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), which competed with the indoles for the radicals. It was found that MLT reacts with .OH with k(r) = 2.7 x 10(10) M(-1) s(-1). Other indoles and KN reacted with .OH radicals with similarly high rates (k(r) > 10(10) M(-1) s(-1)). In contrast to nonhydroxylated indoles (MLT, 6-Cl-MLT, and 5-MeO-T), hydroxylated indoles (5-OH-T and 6-OH-MLT) may function both as .OH promoters and .OH scavengers. The melatonin precursor serotonin promoted the generation of .OH radicals in the presence of ferric iron and H2O2, and the melatonin metabolite 6-hydroxymelatonin generated large quantities of .OH radicals in aerated solutions containing Fe3+ ion, even in the absence of externally added hydrogen peroxide. These reactions may be relevant to the biological action of these physiologically important indolic compounds.