Article

Reaction mechanism of melatonin oxidation by reactive oxygen species in vitro

EA 4466, Département de Biologie Expérimentale, Métabolique et Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France.
Journal of Pineal Research (Impact Factor: 7.81). 04/2011; 50(3):328-35. DOI: 10.1111/j.1600-079X.2010.00847.x
Source: PubMed

ABSTRACT Melatonin (N-acetyl-5-hydroxytryptamine) is a pineal hormone widely known for its antioxidant properties, both in vivo and by direct capture of free radicals in vitro. Although some metabolites and oxidation products of melatonin have been identified, the molecular mechanism by which melatonin exerts its antioxidant properties has not been totally unravelled. This study investigated the reaction mechanism of oxidation of melatonin by radio-induced reactive oxygen species, generated by gamma radiolysis of water for aqueous solutions of melatonin (from 20 to 200 μm), in the presence or absence of molecular oxygen. The hydroxyl radical was found to be the unique species able to initiate the oxidation process, leading to three main products, e.g. N(1)-acetyl-N(2)-formyl-5-methoxykynurenin (AFMK), N(1)-acetyl-5-methoxykynurenin (AMK) and hydroxymelatonin (HO-MLT). The generation of AFMK and HO-MLT strongly depended on the presence of molecular oxygen in solution: AFMK was the major product in aerated solutions (84%), whereas HO-MLT was favoured in the absence of oxygen (86%). Concentrations of AMK remained quite low, and AMK was proposed to result from a chemical hydrolysis of AFMK in solution. A K-value of 1.1 × 10(-4) was calculated for this equilibrium. Both hydrogen peroxide and superoxide dismutase had no effect on the radio-induced oxidation of melatonin, in good accordance for the second case with the poor reactivity of the superoxide anion towards melatonin. Finally, a reaction mechanism was proposed for the oxidation of melatonin in vitro.

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    • "Melatonin (MT) is a secretory product of the pineal gland that participates in many important physiological functions, including seasonal reproduction, immunity, and circadian rhythms (Reiter et al. 2010). Numerous reports have documented protective actions of MT in various models of oxidative stress due to its direct free radical scavenger activity, and its indirect antioxidant properties (Bonnefont-rousselot et al. 2011; Galano et al. 2011; Rodriguez et al. 2004; Tan et al. 1993). This indole stimulates the activity of antioxidant enzymes and has the capacity to detoxify other reactive oxygen and nitrogen species including singlet oxygen ( 1 O 2 ), NO, peroxynitrite anion as well as their metabolites peroxynitrous acid and hydrogen peroxide (Tan et al. 2002). "
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