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) μM. In contrast, serotonin which also scavenged HOCl, was much more effective in decreasing phospholipid peroxidation (IC₅₀ 15 ± 5 μM). Both compounds reacted with trichloromethylperoxyl radical (CCl₃O₂) with rate constants of (2.7 ± 0.2) x 10⁸ and (1.2 ± 0.1) x 10⁸ 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.