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-me thoxytryptamine, MLT) is an important natural antioxidant and free rad ical scavenger [J. Pineal Res., 14:51; 1993]. In the present work we d etermined the rate constants, k(r), for scavenging (OH)-O-. radicals b y melatonin, 5-methoxytryptamine (5-MeO-T), 5-hydroxytryptamine (serot onin, 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)-O-. with k(r ) = 2.7 x 10(10) M-1 s(-1). Other indoles and KN reacted with (OH)-O-. radicals with similarly high rates (k(r) > 10(10) M-1 s(-1)). In cont rast to nonhydroxylated indoles (MLT, 6-Cl-MLT, and 5-MeO-T), hydroxyl ated indoles (5-OH-T and 6-OH-MLT) may function both as (OH)-O-. promo ters and (OH)-O-. scavengers. The melatonin precursor serotonin promot ed the generation of (OH)-O-. radicals in the presence of ferric iron and H2O2, and the melatonin metabolite 6-hydroxymelatonin generated la rge quantities of (OH)-O-. radicals in aerated solutions containing Fe 3+ ion, even in the absence of externally added hydrogen peroxide. The se reactions may be relevant to the biological action of these physiol ogically important indolic compounds. Published by Elsevier Science In c.