Issue 10, 2014

Cyclic 3-hydroxymelatonin, a key metabolite enhancing the peroxyl radical scavenging activity of melatonin

Abstract

The reactions of cyclic 3-hydroxymelatonin (3-OHM) with hydroxyl (˙OH) and hydroperoxyl (˙OOH) radicals were studied using Density Functional Theory. Two environments, mimicking lipid and aqueous solutions, have been modelled. Three mechanisms of reaction were considered: radical adduct formation (RAF), hydrogen transfer (HT), and single electron transfer (SET). Their relative importance for the free radical scavenging activity of 3-OHM was assessed. It was found that 3-OHM reacts with ˙OH at diffusion-limited rates, regardless of the polarity of the environment, which supports its excellent ˙OH radical scavenging activity. The overall reactivity of 3-OHM towards this radical was found to be similar, but slightly higher than those of melatonin and two other metabolites (N1-acetyl-5-methoxykynuramine, AMK; and N1-acetyl-N2-formyl-5-methoxykynuramine, AFMK). For the reaction with ˙OOH, 3-OHM was found to react several orders of magnitude faster, in aqueous solution, than melatonin, AMK and AFMK. Furthermore, under these conditions 3-OHM was found to react with ˙OOH about 98.4 times faster than Trolox. This seems to be a very important finding since it has been proposed that melatonin, AMK and AFMK are rather ineffective as peroxyl radical scavengers, while 3-OHM is predicted to be very efficient. Therefore, it is proposed that the protective effects of melatonin against peroxyl radicals become important after being metabolized into 3-OHM. Accordingly, the results presented in this work not only support the continuous protection against oxidative stress exerted by melatonin, through its free radical scavenging cascade, but also the important role of 3-OHM on the peroxyl radical scavenging activity of melatonin.

Graphical abstract: Cyclic 3-hydroxymelatonin, a key metabolite enhancing the peroxyl radical scavenging activity of melatonin

Article information

Article type
Paper
Submitted
22 Aug. 2013
Accepted
11 Dec. 2013
First published
12 Dec. 2013

RSC Adv., 2014,4, 5220-5227

Cyclic 3-hydroxymelatonin, a key metabolite enhancing the peroxyl radical scavenging activity of melatonin

A. Galano, D. X. Tan and R. J. Reiter, RSC Adv., 2014, 4, 5220 DOI: 10.1039/C3RA44604B

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