On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK

Abstract

OOCCl 3 radicals have been studied using the density functional theory. Three mechanisms of reaction have been considered: radical adduct formation (RAF), hydrogen transfer (HT), and single electron transfer (SET). Their relative importance for the free radical scavenging activity of AFMK and AMK has been assessed. It was found that AFMK and AMK react with˙OH at diffusion-limited rates, regardless of the polarity of the environment, which supports their excellent˙OH radical scavenging activity. Both compounds were found to be also very efficient for scavenging˙OOCCl 3 , but rather ineffective for scavenging˙OOH. Regarding their relative activity, it was found that AFMK systematically is a poorer scavenger than AMK and melatonin. In aqueous solution, AMK was found to react faster than melatonin with all the studied free radicals, while in nonpolar environments, the relative efficiency of AMK and melatonin as free radical scavengers depends on the radical with which they are reacting. Under such conditions, melatonin is predicted to be a better˙OOH and˙OOCCl 3 scavenger than AMK, while AMK is predicted to be slightly better than melatonin for scavenging˙OH. Accordingly it seems that melatonin and its metabolite AMK constitute an efficient team of scavengers able of deactivating a wide variety of reactive oxygen species, under different conditions. Thus, the presented results support the continuous protection exerted by melatonin, through the free radical scavenging cascade.

A Double-Blind, Placebo-Controlled Trial Related to the Effects of Melatonin on Oxidative Stress and Inflammatory Parameters of Obese Women

“…Furthermore, mechanistic studies provide data, validating the powerful anti-inflammatory and antioxidant effects of melatonin [22]. Melatonin and its metabolites directly scavenge free radicals [15] and stimulate the activity and expression of antioxidant enzymes [23][24][25]. It also decreases production of proinflammatory cytokines by suppressing the mRNA expression of TNF-α, IL-1β, IL-6, and iNOS [17,26,27].…”

“…Melatonin (N-acetyl-5-methoxytryptamine) in mammals is synthesized in several cells, tissues, and organs mainly for local utilization (autocrine and paracrine actions) and the circulating melatonin is mostly provided by the pineal gland [11,12]. It is known that melatonin is responsible for regulation of circadian rhythms, immune responses and mood, and reduces oxidative stress [13][14][15][16]. The roles of melatonin in obesity management have been studied in animal models of diet-induced obesity.…”

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…Effectively, melatonin treatment significantly inhibits cholangiocarcinoma development [141]. Melatonin is a special class of antioxidant because when scavenging free radicals, it is processed in a series of metabolites that are also free radical scavengers [144]. In addition to direct scavenger activity, melatonin has a genomic effect, inducing expression of antioxidant enzymes such as glutathione peroxidase, glutathione reductase and superoxide dismutase [145] as well as reducing the expression of pro-oxidative enzymes, e.g., iNOS [118,121].…”

Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm

“…26 In addition, some of the antioxidant actions of melatonin are a consequence of its metabolites. 27 As a result, melatonin may be involved in the pathophysiology of many diseases and its concentrations have been studied in various clinical populations. The changes of melatonin secretion and their role in the pathogenesis, the clinical features and the prognosis of preeclampsia have not been fully clarified.…”