Evaluation of the antioxidant activity of melatonin in vitro

Melatonin is being increasingly promoted as a treatment for ''jet lag'' and insomnia and has been suggested to act as an antioxidant in vivo. The antioxidant and potential pro-oxidant activities of melatonin were investigated in vitro. Melatonin was able to scavenge hypochlorous acid (HOCl) at a rate sufficient to protect catalase against inactivation by this molecule. Melatonin could also prevent the oxidation of 5-thio-2-nitrobenzoic acid by HOCl. Melatonin decreased the peroxidation of ox-brain phospholipids with a calculated IC50 of (210 +/- 2.3) mu M. In contrast, serotonin which also scavenged HOCl, was much more effective in decreasing phospholipid peroxidation (IC50 15 +/- 5 mu M). Both compounds reacted with trichloromethylperoxyl radical (CCl3O2.) with rate constants of (2.7 +/- 0.2) x 10(8) and (1.2 +/- 0.1) x 10(8) M(-1) s(-1) respectively. Melatonin did not scavenge superoxide radical and weakly protected DNA against damage by the ferric bleomycin system. By contrast serotonin was weakly pro-oxidant in the ferric-bleomycin system and strongly pro-oxidant in the Fe3+-EDTA/H2O2-deoxyribose system. Solubility restrictions precluded examination of melatonin in this system. Our data show that melatonin exerts only limited direct antioxidant activities.