Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages

Mayo, Juan C.; Sainz, Rosa M.; Tan, Dun Xian; Hardeland, Rüdiger; León, Josefa; Rodríguez, Carmen; Reíter, Russel J.

doi:10.1016/j.jneuroim.2005.05.002

Cited by 282 publications

(207 citation statements)

References 51 publications

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“…Recently, by using computer graphics applications, it has been described that melatonin has an excellent steric and electronic effect that is complementary with COX and, therefore, it seems possible that melatonin might bind to the active site of COX-1 and COX-2, modulating the activity of this enzyme (De la Rocha et al, 2007). Anti-inflammatory actions of melatonin, in which this indolamine specifically prevents the activation of the COX-2 enzyme, have also been described in vitro in cultures of C6 glioma cells (Esposito et al, 2008) and in macrophages (Mayo et al, 2005). Melatonin at physiological (1 nM) doses reduced aromatase mRNA steady-state levels both under basal conditions and when aromatase mRNA expression was stimulated by adding PGE 2 .…”

Section: Discussionmentioning

confidence: 93%

Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

et al. 2009

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BACKGROUND: Melatonin reduces the development of breast cancer interfering with oestrogen-signalling pathways, and also inhibits aromatase activity and expression. Our objective was to study the promoters through which melatonin modifies aromatase expression, evaluate the ability of melatonin to regulate cyclooxygenases and assess whether the effects of melatonin are related to its effects on intracellular cAMP, in MCF-7 cells. METHODS: Total aromatase mRNA, aromatase mRNA promoter regions and cyclooxygenases mRNA expression were determined by real-time RT -PCR. PGE 2 and cAMP were measured by kits. RESULTS: Melatonin downregulated the gene expression of the two major specific aromatase promoter regions, pII and pI.3, and also that of the aromatase promoter region pI.4. Melatonin 1 nM was able to counteract the stimulatory effect of tetradecanoyl phorbol acetate on PGE 2 production and inhibit COX-2 and COX-1 mRNA expression. Melatonin 1 nM elicited a parallel time-dependent decrease in both cyclic AMP formation and aromatase mRNA expression. CONCLUSIONS: This study shows that melatonin inhibits aromatase activity and expression by regulating the gene expression of specific aromatase promoter regions. A possible mechanism for these effects would be the regulation by melatonin of intracellular cAMP levels, mediated by an inhibition of cyclooxygenase activity and expression.

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Section: Discussionmentioning

confidence: 93%

Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

et al. 2009

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“…The response may be limited because of other actions by melatonin and its oxidatively formed metabolites. In peripheral monocytes, melatonin and, even more, AFMK suppressed TNF-and IL-8 production [124] and, in macrophages, cyclooxygenase-2 and iNOS expression [24,86]. Moreover, melatonin was found to be efficiently oxidized to AFMK by macrophages [124].…”

Section: The Kynuramine Pathwaymentioning

confidence: 98%

“…AMK is of high interest because of several properties. It is a potent antioxidant [110], effective scavenger of reactive nitrogen species [36,42,43], protecting agent against mitochondrial damage [1,38,40,41], downregulator of cyclooxygenase-2 [24,86], cyclooxygenase inhibitor by far more potent than aspirin [62], and antagonist of neuronal [71] and inducible NO synthases [24,143].…”

Section: The Kynuramine Pathwaymentioning

confidence: 99%

Melatonin Metabolism in the Central Nervous System

Hardeland¹

2010

113

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Abstract:The metabolism of melatonin in the central nervous system is of interest for several reasons. Melatonin enters the brain either via the pineal recess or by uptake from the blood. It has been assumed to be also formed in some brain areas. Neuroprotection by melatonin has been demonstrated in numerous model systems, and various attempts have been undertaken to counteract neurodegeneration by melatonin treatment. Several concurrent pathways lead to different products. Cytochrome P 450 subforms have been demonstrated in the brain. They either demethylate melatonin to Nacetylserotonin, or produce 6-hydroxymelatonin, which is mostly sulfated already in the CNS. Melatonin is deacetylated, at least in pineal gland and retina, to 5-methoxytryptamine. N 1 -acetyl-N 2 -formyl-5-methoxykynuramine is formed by pyrrole-ring cleavage, by myeloperoxidase, indoleamine 2,3-dioxygenase and various non-enzymatic oxidants. Its product, N 1 -acetyl-5-methoxykynuramine, is of interest as a scavenger of reactive oxygen and nitrogen species, mitochondrial modulator, downregulator of cyclooxygenase-2, inhibitor of cyclooxygenase, neuronal and inducible NO synthases. Contrary to other nitrosated aromates, the nitrosated kynuramine metabolite, 3-acetamidomethyl-6-methoxycinnolinone, does not re-donate NO. Various other products are formed from melatonin and its metabolites by interaction with reactive oxygen and nitrogen species. The relative contribution of the various pathways to melatonin catabolism seems to be influenced by microglia activation, oxidative stress and brain levels of melatonin, which may be strongly changed in experiments on neuroprotection. Many of the melatonin metabolites, which may appear in elevated concentrations after melatonin administration, possess biological or pharmacological properties, including N-acetylserotonin, 5-methoxytryptamine and some of its derivatives, and especially the 5-methoxylated kynuramines.

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“…Melatonin is able to suppresses COX-2 production. Mayo et al (2005) examined the anti-inflammatory effect of melatonin and its metabolites, AFMK and AMK, by preventing COX-2 and iNOS activation and reducing its products, including PGE2 and nitric oxide. They revealed that melatonin has no effect on COX-1 and selectively inhibits COX-2 only.…”

Section: Effect Of Melatonin On Immune Mediatorsmentioning

confidence: 99%

The melatonin immunomodulatory actions in radiotherapy

et al. 2017

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Radiotherapy has a key role in cancer treatment in more than half of patients with cancer. The management of severe side effects of this treatment modality is a limiting factor to appropriate treatment. Immune system responses play a pivotal role in many of the early and late side effects of radiation. Moreover, immune cells have a significant role in tumor response to radiotherapy, such as angiogenesis and tumor growth. Melatonin as a potent antioxidant has shown appropriate immune regulatory properties that may ameliorate toxicity induced by radiation in various organs. These effects are mediated through various modulatory effects of melatonin in different levels of tissue reaction to ionizing radiation. The effects on the DNA repair system, antioxidant enzymes, immune cells, cytokines secretion, transcription factors, and protein kinases are most important. Moreover, anti-cancer properties of melatonin may increase the therapeutic ratio of radiotherapy. Clinical applications of this agent for the management of malignancies such as breast cancer have shown promising results. It seems anti-proliferative, anti-angiogenesis, and stimulation or suppression of some immune cell responses are the main anti-tumor effects of melatonin that may help to improve response of the tumor to radiotherapy. In this review, the effects of melatonin on the modulation of immune responses in both normal and tumor tissues will be discussed.

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Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages

Cited by 282 publications

References 51 publications

Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells

Melatonin Metabolism in the Central Nervous System

The melatonin immunomodulatory actions in radiotherapy

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